transforming-growth-factor-beta and Food-Hypersensitivity

Topics: Administration, Oral; Allergens; Animals; Dendritic Cells; Food Hypersensitivity; Forkhead Transcription Factors; Humans; Immune Tolerance; Immunologic Factors; Immunotherapy; Intestinal Mucosa; Intestines; Peptides; Protein Precursors; T-Lymphocytes, Regulatory; Transforming Growth Factor beta

Dendritic cells (DCs) mediate tolerance to food antigens, limit reactivity to the gut microbiota and are required for optimal response to intestinal pathogens. Intestinal DCs are heterogeneous but collectively generate both regulatory and effector T cell responses. The balance of outcomes is determined by the activity of functionally distinct DC subsets and their modulation by environmental cues. DCs constantly sample luminal content to monitor for pathogens; the significance of the various pathways by which this occurs is incompletely understood. Intestinal DC have distinctive properties shaped by local host, dietary and microbial signals. These properties include the ability to produce all-trans retinoic acid (RA) and imprint gut tropism on T cells they activate. In the steady-state, subsets of intestinal DC are potent generators of inducible Treg, aided by their ability to activate TGFβ and produce RA. However, responses induced by steady-state intestinal DCs are not exclusively regulatory in nature; effector T cells with specificity for commensal bacterial can be found in the healthy mucosa and these can be locally controlled to prevent inflammation. The ability of intestinal DCs to enhance effector responses in infection or sustain inflammation in disease is likely to involve both modulation of the local DC population and recruitment of additional populations. Immune pathways in the pathogenesis of inflammatory bowel disease can be mapped to DCs and in inflamed intestinal tissue, DCs show increased expression of microbial recognition machinery, activation, and production of key immunological mediators. Intestinal DCs may be targeted for disease therapy or to improve vaccine responses.

Topics: Allergens; Animals; Cell Communication; Colitis; Dendritic Cells; Disease Models, Animal; Food Hypersensitivity; Gastrointestinal Microbiome; Humans; Immunity, Mucosal; Immunologic Factors; Intestinal Mucosa; Intraepithelial Lymphocytes; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Tretinoin

Food protein-induced enterocolitis syndrome (FPIES) is a poorly understood non-IgE-mediated food hypersensitivity, primarily affecting infants and toddlers. There are few data regarding pathophysiology of FPIES that suggest local intestinal imbalance between TNF-α and TGF-β. Patients frequently present with multiple reactions, which are characterized by projectile, repetitive emesis, dehydration, lethargy, and failure to thrive. Despite the severity of presentation, the diagnosis is frequently delayed, and patients often undergo extensive and invasive evaluation prior to reaching the diagnosis.. Reviews published in the last year provide a general approach to diagnosis and management of FPIES and aim to increase awareness and understanding of FPIES among general pediatricians.. Multicenter studies are necessary to reevaluate and modify the oral food challenge criteria. Research on the pathophysiology of FPIES reactions is necessary to provide insight into the evidence-based approach to diagnosis and management of FPIES. Registries are needed to understand the phenotype, triggers, and prevalence of FPIES.

Topics: Child, Preschool; Dietary Proteins; Enterocolitis; Food Hypersensitivity; Humans; Infant; Infant, Newborn; Syndrome; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Breast milk cytokines have the potential to regulate the immune response to food antigens in infants. Cytokines are present in all mammalian milks and are capable of inhibiting excess inflammation and modulating epithelial proliferation. There are a range of candidate cytokines in milk such as transforming growth factor-beta (TGF-beta), the major cytokine present, and interleukin-10, which play a role in immune regulation in the developing infant. This article will be a review of the current literature with regard to TGF-beta in infant immune development. Our data on supplementation of formula with rTGF-beta2 will be discussed in view of the current literature. Oral antigen exposure also plays an important role in priming the developing immune response. The influence of early introduction of oral beta-lactoglobulin in allergy prone rat pups will also be discussed.

Topics: Allergens; Animals; Food Hypersensitivity; Humans; Immune Tolerance; Infant; Inflammation; Interleukin-10; Milk, Human; Transforming Growth Factor beta

Biomarkers are objectively measured indicators of normal and abnormal biologic processes and may vary with therapeutic interventions. In the area of gastrointestinal diseases, biomarker research is primarily in the area of cancer biology. Little is known about biomarkers in connection with other gastrointestinal disorders. This article reviews biomarker data for nononcologic gastrointestinal processes with a focus on allergic disorders.

Topics: Biomarkers; Chemokine CCL26; Chemokines, CC; Eosinophils; Food Hypersensitivity; Gastrointestinal Diseases; Humans; Immunoglobulin E; Interleukin-13; Interleukin-2 Receptor alpha Subunit; Mast Cells; Matrix Metalloproteinase 9; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A

Eosinophil-associated gastrointestinal disorders (EGIDs) are characterized by an inappropriate accumulation of eosinophils within the gastrointestinal tract. The underlying etiology and pathophysiology that lead to the development of EGID are far from elucidated. However, there is growing evidence to support the role of aeroallergens and food allergens in the pathogenesis of these disorders. Recent advances have highlighted the role of Th2-driven cytokines in the development of EGID, and clinical studies have verified that children and adults with EGID often have positive skin testing to food allergens. The most common form of EGID, eosinophilic esophagitis (EE), has garnered intense investigation following an increased recognition over the past decade. Recently, there have been several important studies providing insight into both the cellular mechanisms governing EE and clinical therapies directed toward the treatment of EE. In the article herein, we will review the most recent scientific advances influencing our understanding of EGID with special emphasis on the role of allergens in the pathogenesis of EGID.

Topics: Allergens; Animals; Eosinophils; Food Hypersensitivity; Gastrointestinal Diseases; Humans; Interleukin-13; Interleukin-5; Smad Proteins; Th2 Cells; Transforming Growth Factor beta; Vascular Cell Adhesion Molecule-1

Early feeding with cows' milk (CM) may cause cows' milk allergy (CMA). Breast milk contains many immune factors which compensate for the undeveloped defence mechanisms of the gut of the newborn infant. We studied the effect of supplementary CM feeding at the maternity hospital on the subsequent incidence of CMA, the effects of formula and breast feeding on the subsequent immunologic types of CMA, and the importance of immune factors present in colostrum in the immune responses of infants with CMA. In a cohort of 6209 infants, 824 were exclusively breast-fed and 87% required supplementary milk while in the maternity hospital: 1789 received CM formula, 1859 pasteurized human milk, and 1737 whey hydrolysate formula. The cumulative incidence of CMA, verified by a CM elimination-challenge test, was 2.4% in the CM, 1.7% in the pasteurized human milk and 1.5% in the whey hydrolysate group. Among these infants, exposure to CM at hospital and a positive atopic heredity increased the risk of CMA. Of the exclusively breast-fed infants, 2.1% had CMA. Risk factors for the development of IgE-mediated CMA were: exposure to CM at hospital, breast-feeding during the first 8 weeks at home either exclusively or combined with infrequent exposure to small amounts of CM and long breast-feeding. The content of transforming growth factor-beta1 (TGF-beta1) in colostrum from mothers of infants with IgE-mediated CMA was lower than from mothers of infants with non-IgE-mediated CMA. In infants with CMA, TGF-beta1 in colostrum negatively correlated with the result of skin prick test and the stimulation of peripheral blood mononuclear cells to CM, but positively with infants' IgA and IgG antibodies to CM proteins. Feeding of CM formula at maternity hospital increases the risk of CMA, but exclusive breast-feeding does not eliminate the risk. Prolonged breast-feeding exclusively or combined with infrequent exposure to small amounts of CM during the first 8 weeks induces the development of IgE-mediated CMA. Colostral TGF-beta1 may inhibit IgE- and cell mediated reactions and promote IgG-IgA antibody production to CM in infants prone to developing CMA.

Topics: Animals; Bottle Feeding; Breast Feeding; Cattle; Cohort Studies; Colostrum; Female; Food Hypersensitivity; Humans; Immunoglobulin A; Immunoglobulin E; Infant; Infant Food; Infant, Newborn; Lactation; Milk; Milk Hypersensitivity; Milk Proteins; Milk, Human; Prospective Studies; Risk Factors; Time Factors; Transforming Growth Factor beta

Atopic Dermatitis (AD) is a multifactorial cutaneous disorder associated with chronic inflammation of the skin. Growing evidence points to TGF-β/SMAD signaling as a key player in mediating inflammation and the subsequent tissue remodeling, often resulting in fibrosis. This study investigates the role of a core transcription factor involved in TGF-β signaling i.e., SMAD3 genetic variants (rs4147358) in AD predisposition and its association with SMAD3 mRNA expression, serum IgE levels, and sensitization to various allergens in AD patients.. A total of 246 subjects including 134 AD cases and 112 matched healthy controls were genotyped for SMAD3 intronic SNP by PCR-RFLP. mRNA expression of SMAD3 was determined by quantitative Real-Time PCR (qRT-PCR), Vitamin-D levels by chemiluminescence, and total serum IgE levels by ELISA. In-vivo allergy testing was performed for the evaluation of allergic reactions to house dust mites (HDM) and food allergens.. A significantly higher frequency of mutant genotype AA (cases: 19.4% vs controls: 8.9%) (OR = 2.8, CI = 1.2 - 6.7, p = 0.01) was observed in AD cases. The mutant allele 'A' also showed a 1.9-fold higher risk for AD compared to the wild allele 'C' indicating that the carriers of the A allele have a higher risk for AD predisposition (OR-1.9, CI = 1.3-2.8, p < 0.001). In addition, quantitative analysis of SMAD3 mRNA in peripheral blood showed 2.8-fold increased expression in AD cases as compared to healthy controls. Stratification analysis revealed the association of the mutant AA genotype with deficient serum Vitamin D levels (p = 0.02) and SMAD3 mRNA overexpression with HDM sensitization (p = 0.03). Furthermore, no significant association of genotypes with SMAD3 mRNA expression was observed.. Our study indicates that SMAD3 intronic SNP bears a significant risk of AD development. Moreover, overexpression of SMAD3 mRNA and its association with HDM sensitization highlights the possible role of this gene in AD pathogenesis.

Topics: Allergens; Animals; Case-Control Studies; Dermatitis, Atopic; Food Hypersensitivity; Humans; Immunoglobulin E; Inflammation; Pyroglyphidae; Smad3 Protein; Transforming Growth Factor beta

Hypoallergenic formulas are recommended for infants who are not breastfed and cannot tolerate cow milk formulas due to allergy. These formulas are hydrolyzed to break down larger protein chains into shorter, easy-to-digest, and potentially less allergenic proteins. Hydrolysis, however, possibly occurs at the expense of the transforming growth factor beta (TGF-β) and anti-inflammatory activity that is inherent in regular formula. Our objective was to determine the TGF-β and the anti-inflammatory activity of commercially available hypoallergenic and regular formulas. Human gingival fibroblasts were incubated with reconstituted formulas followed by detection of TGF-β target genes and activation of Smad2/3 signaling. Gingival fibroblasts and the oral squamous cell carcinoma cell line HSC-2 were also exposed to formulas before adding interleukin (IL)1β and tumor necrosis factor (TNF)α to provoke expression of pro-inflammatory cytokines. For murine bone marrow-derived macrophages, pro-inflammatory cytokine expression was stimulated with saliva. Changes in p65 nuclear translocation and phosphorylation of smad3 and p38 were analyzed by immunostaining. Our study demonstrated that regular formula, but not hypoallergenic formula, enhanced the expression of TGF-β target genes IL11, PRG4, and NOX4 in gingival fibroblasts. Hypoallergenic formulas also failed to initiate nuclear translocation of Smad2/3 and phosphorylation of Smad3. Moreover, regular formulas were more potent than hypoallergenic formulas in reducing the expression of pro-inflammatory cytokines in gingival fibroblasts, HSC-2 epithelial cells, and murine bone marrow macrophages. Hypoallergenic and regular formulas had a similar capacity to reduce p65 nuclear translocation and phosphorylation of p38 in fibroblasts. These findings suggest that hypoallergenic formulas lack in vitro TGF-β activity and have a lower anti-inflammatory activity compared with regular formulas.

Topics: Animals; Anti-Inflammatory Agents; Cattle; Cell Line, Tumor; Cytokines; Fibroblasts; Food Hypersensitivity; Humans; Infant; Infant Formula; Mice; Milk; Signal Transduction; Smad2 Protein; Smad3 Protein; Transforming Growth Factor beta

Food allergies have become a major healthcare concern, hence preventive efforts to ensure oral tolerance induction to newly introduced antigens are particularly relevant. Given that transforming growth factor-β (TGF-β) plays a key role in immune tolerance, we tested whether an infant formula enriched with TGF-β would improve oral tolerance induction. A partially hydrolyzed whey protein-based formula was enriched with cow's-milk-derived TGF-β (TGF-β-enriched formula) by adding a specific whey protein isolate (WPI). The manufacturing process was optimized to achieve a concentration of TGF-β within the range of human breast milk concentrations. Protection from allergic sensitization and immune response was assessed in a mouse model. Adult mice received the TGF-β-enriched formula, a control non-enriched formula, or water ad libitum for 13 days before sensitization and suboptimal tolerization to ovalbumin (OVA). When compared to non-tolerized mice, suboptimally-tolerized mice supplemented with the TGF-β-enriched formula showed significantly lower levels of total immunoglobulin-E (IgE) and OVA-specific (IgG1). Mouse mast-cell protease-1 (mMCP-1) and cytokine levels were also significantly decreased in suboptimally-tolerized mice fed the TGF-β-enriched formula. In conclusion, oral supplementation with cow's-milk-derived TGF-β decreased allergic responses to newly introduced allergens and thus reduced the risk of developing food allergy.

Topics: Allergens; Animals; Cattle; Chymases; Cytokines; Female; Food Hypersensitivity; Humans; Immune Tolerance; Immunoglobulin G; Infant; Infant Formula; Mice; Mice, Inbred C57BL; Milk; Ovalbumin; Transforming Growth Factor beta; Whey Proteins

The attempt to induce oral tolerance as a treatment for food allergy has been hampered by a lack of sustained clinical protection. Immunotherapy by nonoral routes, such as the skin, may be more effective for the development of maintained tolerance to food allergens.. We sought to determine the efficacy and mechanism of tolerance induced by epicutaneous immunotherapy (EPIT) in a model of food-induced anaphylaxis.. C3H/HeJ mice were sensitized to ovalbumin (OVA) orally or through the skin and treated with EPIT using OVA-Viaskin patches or oral immunotherapy using OVA. Mice were orally challenged with OVA to induce anaphylaxis. Antigen-specific regulatory T (Treg)-cell induction was assessed by flow cytometry using a transgenic T-cell transfer model.. By using an adjuvant-free model of food allergy generated by epicutaneous sensitization and reactions triggered by oral allergen challenge, we found that EPIT induced sustained protection against anaphylaxis. We show that the gastrointestinal tract is deficient in de novo generation of Treg cells in allergic mice. This defect was tissue-specific, and epicutaneous application of antigen generated a population of gastrointestinal-homing LAP. Our data highlight the immune communication between skin and gastrointestinal tract, and identifies novel mechanisms by which epicutaneous tolerance can suppress food-induced anaphylaxis.

Topics: Administration, Cutaneous; Allergens; Anaphylaxis; Animals; Arachis; Cholera Toxin; Desensitization, Immunologic; Food Hypersensitivity; Forkhead Transcription Factors; Immunoglobulin G; Mice, Inbred BALB C; Mice, Inbred C3H; Ovalbumin; Peptides; T-Lymphocytes, Regulatory; Transforming Growth Factor beta

Oral tolerance induction in early life is a promising approach for food allergy prevention. Its success requires the identification of factors necessary for its persistence.. We aimed to assess in mice duration of allergy prevention by breastfeeding-induced oral tolerance and whether oral TGF-β supplementation after weaning would prolong it.. We quantified ovalbumin (OVA) and OVA-specific immunoglobulin levels by ELISA in milk from the EDEN birth cohort. As OVA-specific Ig was found in all samples, we assessed whether OVA-immunized mice exposed to OVA during lactation could prevent allergic diarrhoea in their 6- and 13-week-old progeny. In some experiments, a TGF-β-enriched formula was given after weaning.. At 6 weeks, only 13% and 34% of mice breastfed by OVA-exposed mothers exhibited diarrhoea after six and seven OVA challenges vs. 44% and 72% in mice breastfed by naïve mothers (P = 0.02 and 0.01). Protection was associated with decreased levels of MMCP1 and OVA-specific IgE (P < 0.0001). At 13 weeks, although OVA-specific IgE remained low (P = 0.001), diarrhoea occurrence increased to 32% and 46% after six and seven OVA challenges in mice breastfed by OVA-exposed mothers. MMCP1 levels were not significantly inhibited. Supplementation with TGF-β after weaning induced a strong protection in 13-week-old mice breastfed by OVA-exposed mothers compared with mice breastfed by naive mothers (0%, 13% and 32% of diarrhoea at the fifth, sixth and seventh challenges vs. 17, 42 and 78%; P = 0.05, 0.0043 and 0.0017). MMCP1 levels decreased by half compared with control mice (P = 0.02). Prolonged protection was only observed in mice rendered tolerant by breastfeeding and was associated with an improved gut barrier.. In mice, prevention of food allergy by breastfeeding-induced tolerance is of limited duration. Nutritional intervention by TGF-β supplementation after weaning could prolong beneficial effects of breast milk on food allergy prevention.

Topics: Animal Feed; Animals; Antibody Specificity; Breast Feeding; Diarrhea; Food Hypersensitivity; Humans; Immune Tolerance; Immunoglobulin E; Immunoglobulin G; Intestinal Mucosa; Mice; Milk, Human; Ovalbumin; T-Lymphocyte Subsets; Transforming Growth Factor beta; Weaning

Food allergy is a major health burden in early childhood. Infants who develop food allergy display a proinflammatory immune profile in cord blood, but how this is related to interleukin-4 (IL-4)/T helper 2 (T(H)2)-type immunity characteristic of allergy is unknown. In a general population-derived birth cohort, we found that in infants who developed food allergy, cord blood displayed a higher monocyte to CD4(+) T cell ratio and a lower proportion of natural regulatory T cell (nT(reg)) in relation to duration of labor. CD14(+) monocytes of food-allergic infants secreted higher amounts of inflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor-α) in response to lipopolysaccharide. In the presence of the mucosal cytokine transforming growth factor-β, these inflammatory cytokines suppressed IL-2 expression by CD4(+) T cells. In the absence of IL-2, inflammatory cytokines decreased the number of activated nT(reg) and diverted the differentiation of both nT(reg) and naïve CD4(+) T cells toward an IL-4-expressing nonclassical TH2 phenotype. These findings provide a mechanistic explanation for susceptibility to food allergy in infants and suggest anti-inflammatory approaches to its prevention.

Topics: Cell Differentiation; Fetal Blood; Food Hypersensitivity; Humans; Immunity, Innate; Infant; Inflammation Mediators; Interleukin-2; Monocytes; T-Lymphocytes, Regulatory; Th2 Cells; Transforming Growth Factor beta

The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA) during the suckling period on the development of the immune system and oral tolerance (OT) in offspring. Dams were randomized to consume one of two nutritionally adequate diets throughout the suckling period: control (N = 12, 0% DHA) or DHA (N = 8, 0.9% DHA) diet. At 11 days, pups from each dam were randomly assigned to a mucosal OT challenge: the placebo or the ovalbumin (OVA) treatment. At three weeks, plasma immunoglobulins and splenocyte cytokine production ex vivo were measured. OVA-tolerized pups had a lower Th2 (IL-13) response to OVA despite the presence of more activated T cells and memory cells (CD27+, all p < 0.05). Feeding a high DHA diet improved the ability of splenocytes to respond to mitogens toward a skewed Th1 response and led to a higher IL-10 and a lower TGF-β production after stimulation with OVA (all p < 0.05). Untolerized DHA-fed pups had lower plasma concentrations of OVA-specific immunoglobulin E (p for interaction < 0.05). Overall, feeding a high DHA maternal diet improves the tolerance response in untolerized suckled pups in a direction that is thought to be beneficial for the establishment of OT.

Topics: Animals; Dietary Supplements; Docosahexaenoic Acids; Egg Proteins; Female; Food Hypersensitivity; Immune Tolerance; Immunoglobulin E; Interleukin-10; Lactation; Maternal Nutritional Physiological Phenomena; Ovalbumin; Pregnancy; Rats, Sprague-Dawley; Spleen; T-Lymphocytes; Th1-Th2 Balance; Transforming Growth Factor beta

Oral immunotherapy has had limited success in establishing tolerance in food allergy, reflecting failure to elicit an effective regulatory T (Treg) cell response. We show that disease-susceptible (Il4ra(F709)) mice with enhanced interleukin-4 receptor (IL-4R) signaling exhibited STAT6-dependent impaired generation and function of mucosal allergen-specific Treg cells. This failure was associated with the acquisition by Treg cells of a T helper 2 (Th2)-cell-like phenotype, also found in peripheral-blood allergen-specific Treg cells of food-allergic children. Selective augmentation of IL-4R signaling in Treg cells induced their reprogramming into Th2-like cells and disease susceptibility, whereas Treg-cell-lineage-specific deletion of Il4 and Il13 was protective. IL-4R signaling impaired the capacity of Treg cells to suppress mast cell activation and expansion, which in turn drove Th2 cell reprogramming of Treg cells. Interruption of Th2 cell reprogramming of Treg cells might thus provide candidate therapeutic strategies in food allergy.

Topics: Adolescent; Allergens; Animals; Cellular Reprogramming; Child; Child, Preschool; Female; Food Hypersensitivity; Gastric Mucosa; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Immune Tolerance; Immunity, Mucosal; Infant; Interleukin-13; Interleukin-4; Male; Mast Cells; Mice; Mice, Transgenic; Receptors, Cell Surface; Signal Transduction; STAT6 Transcription Factor; T-Lymphocytes, Regulatory; Th2 Cells; Transforming Growth Factor beta

Restoration of the antigen (Ag)-specific immune tolerance in an allergic environment is refractory. B cells are involved in immune regulation. Whether B cells facilitate the generation of Ag-specific immune tolerance in an allergic environment requires further investigation. This paper aims to elucidate the mechanism by which B cells restore the Ag-specific immune tolerance in an allergic environment. In this study, a B cell-deficient mouse model was created by injecting an anti-CD20 antibody. The frequency of tolerogenic dendritic cell (TolDC) was assessed by flow cytometry. The levels of cytokines were determined by enzyme-linked immunosorbent assay. The expression of thrombospondin-1 (TSP1) was assessed by quantitative real-time RT-PCR, Western blotting, and methylation-specific PCR. The results showed that B cells were required in the generation of the TGF-β-producing TolDCs in mice. B cell-derived TSP1 converted the latent TGF-β to the active TGF-β in DCs, which generated TGF-β-producing TolDCs. Exposure to IL-13 inhibited the expression of TSP1 in B cells by enhancing the TSP1 gene DNA methylation. Treating food allergy mice with Ag-specific immunotherapy and IL-13 antagonists restored the generation of TolDCs and enhanced the effect of specific immunotherapy. In conclusion, B cells play a critical role in the restoration of specific immune tolerance in an allergic environment. Blocking IL-13 in an allergic environment facilitated the generation of TolDCs and enhanced the therapeutic effect of immunotherapy.

Topics: Animals; B-Lymphocytes; Dendritic Cells; Desensitization, Immunologic; DNA Methylation; Food Hypersensitivity; Immune Tolerance; Interleukin-13; Male; Mice; Thrombospondin 1; Transforming Growth Factor beta

To explore the effect of non-methylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODN) on serum transforming growth factor (TGF)-β and immune regulation in ovalbumin (OVA)-sensitized young mice.. Thirty female BALB/c mice (2-3 weeks old) were randomly divided into control, model, and CpG-ODN intervention groups. A young mouse model of food allergy was established by OVA sensitization. Normal saline of the same volume was used for replacement in the control group. The mice in the intervention group were intraperitoneally injected with CpG-ODN solution 1 hour before every OVA sensitization. Allergic symptoms were observed and scored for each group. The jejunal tissue was histopathologically examined with hematoxylin-eosin staining. Serum OVA-IgE level was measured using ELISA. Serum concentrations of interleukin (IL)-4, interferon (IFN)-γ, and TGF-β were determined by CBA.. Allergic symptoms were observed in the model group and the jejunal tissue showed the pathological characteristics of type I allergic reaction. The allergic symptom scores in the model and CpG-ODN intervention groups were significantly higher than in the control group (P<0.01). The serum levels of OVA-IgE, IL-4, and TGF-β were significantly higher in the model group than in the control and CpG-ODN intervention groups (P<0.05). The CpG-ODN intervention group had significantly higher serum levels of OVA-IgE, IL-4, and TGF-β than the control group (P<0.05). Compared with the control and CpG-ODN intervention groups, the model group had a significantly reduced IFN-γ level (P<0.05).. The serum TGF-β level is increased in the young mouse model of OVA-sensitized food allergy and is involved in the allergy mechanism. Non-methylated CpG-ODN can reduce the serum TGF-β level in sensitized young mice and play an immunoregulatory role in food allergy.

Topics: Aging; Animals; DNA Methylation; Female; Food Hypersensitivity; Immunoglobulin E; Interleukin-4; Mice; Mice, Inbred BALB C; Oligodeoxyribonucleotides; Ovalbumin; Transforming Growth Factor beta

The neonatal period is often polarised to T helper (Th2) response at the time of birth, predisposing offspring to allergic disorders. Passive immunity through the mother's milk is critical for immune system development of newborns. Probiotics have been proposed to harmonise Th1/Th2 imbalance in allergic conditions in adults. In the present study, the anti-allergic effects of feeding probiotic Lactobacillus rhamnosus-fermented milk (PFM) either to dams during the suckling period or to their offspring after weaning individually or else in successive periods against ovalbumin (OVA)-induced allergy in newborns was analysed. After allergen sensitisation, physical symptoms of allergy, gut immune response, humoral immune response and cell-mediated response through interleukins were detected. Consumption of PFM by mothers and offspring showed a reduction (P<0·01) in physical allergic symptoms in newborns with an increase (P<0·01) in the numbers of goblet and IgA+ cells in the small intestine. Similarly, considerable (P<0·001) decreases in OVA-specific antibodies (IgE, IgG, IgG1) and ratios of IgE/IgG2a and IgG1/IgG2a in the sera of newborn mice were recorded. A decrease in IL-4 and an increase in interferon-γ levels further confirmed the shift from Th2 to Th1 pathway in PFM-fed mice. It is logical to conclude that the timing of PFM intervention in alleviating allergic symptoms is critical, which was found to be most effective when mothers were fed during the suckling period.

Topics: Allergens; Animals; Anti-Allergic Agents; Chemokine CCL2; Cyclooxygenase 2; Female; Fermentation; Food Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Interferon-gamma; Interleukin-10; Interleukin-4; Intestines; Lacticaseibacillus rhamnosus; Male; Mice; Milk; Ovalbumin; Probiotics; Th1 Cells; Th2 Cells; Toll-Like Receptor 2; Toll-Like Receptor 4; Transforming Growth Factor beta

The induction of peripheral tolerance may constitute a disease-modifying treatment for allergic patients. We studied how oral immunotherapy (OIT) with milk proteins controlled allergy in sensitized mice (cholera toxin plus milk proteins) upon exposure to the allergen. Symptoms were alleviated, skin test was negativized, serum specific IgE and IgG1 were abrogated, a substantial reduction in the secretion of IL-5 and IL-13 by antigen-stimulated spleen cells was observed, while IL-13 gene expression in jejunum was down-regulated, and IL-10 and TGF-β were increased. In addition, we observed an induction of CD4+CD25+FoxP3+ cells and IL-10- and TGF-β-producing regulatory T cells in the lamina propria. Finally, transfer experiments confirmed the central role of these cells in tolerance induction. We demonstrated that the oral administration of milk proteins pre- or post-sensitization controlled the Th2-immune response through the elicitation of mucosal IL-10- and TGF-β-producing Tregs that inhibited hypersensitivity symptoms and the allergic response.

Topics: Animals; Cholera Toxin; Disease Models, Animal; Food Hypersensitivity; Immunotherapy; Interleukin-10; Interleukin-13; Interleukin-5; Male; Mice; Milk Proteins; T-Lymphocytes, Regulatory; Transforming Growth Factor beta

Food protein-induced allergic proctocolitis (FPIAP) is mostly a non-immunoglobulin E-mediated disease where a T-cell-mediated reaction to cow's milk protein has been suggested. We determined the expression of transforming growth factor (TGF)-β, TGF-β receptor-1, tumor necrosis factor (TNF)-α, CD86, and CD23 on the colon mucosa to investigate their roles in the pathogenesis of the two subtypes of FPIAP, i.e. infantile FPIAP and FPIAP in older children.. Group 1 comprised children with infantile FPIAP (age <6 months, n = 21), group 2 referred to FPIAP in older children (age >1.5 years, n = 7), and group 3 included children with juvenile hyperplastic polyps (n = 22). Immunohistochemical staining of colonic biopsy specimens was performed.. The expression of TNF-α was significantly higher in groups 1 and 2 compared to group 3. Group 2 patients had a significantly lower TGF-β expression compared to the other groups. The expression of CD86 was higher in group 1 than in group 3 (p = 0.012). Eosinophil counts per high-power field in the lamina propria were significantly correlated with CD86 expression (p = 0.026, r = 0.388).. Our results suggest that TNF-α is implicated in the pathogenesis of both types of FPIAP. The decreased activity of TGF-β receptor-1 accompanied by the increased expression of CD86 in infants and the decreased activity of TGF-β in older children appear to play a role in the development of FPIAP.

Topics: B7-2 Antigen; Biopsy; Child, Preschool; Colitis; Cytokines; Enterocolitis; Female; Food Hypersensitivity; Humans; Immunoglobulin E; Infant; Intestinal Mucosa; Male; Milk Hypersensitivity; Protein Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type I; Receptors, IgE; Receptors, Transforming Growth Factor beta; Transforming Growth Factor beta

Allergy is a skewed T helper (Th)2 polarization response in the body; its treatment is not satisfactory currently. Oral tolerance dysfunction plays a critical role in the pathogenesis of allergy. The present study aims to restore the breached intestinal tolerance with an artificial adduct of a measles virus C protein-derived small peptide (MVCP) and a model antigen, ovalbumin (MOA), and to observe the effect of MOA on inhibition of intestinal allergy in a mouse model. The MOA was formed by the MVCP and ovalbumin. The effect of MOA on regulation of the properties of dendritic cells (DC) and CD4(+) T cells was observed with a cell culture model and a mouse model of the gut Th2 pattern inflammation. After treatment with MOA, mouse intestinal DCs showed high levels of aldehyde dehydrogenase (ALDH) activity and expressed transforming growth factor (TGF)-beta; the frequency of Treg in the intestine was also significantly increased. The treatment with MOA efficiently suppressed the antigen-specific Th2 pattern inflammation in the intestine. Administration with the MOA can induce the development of antigen-specific oral tolerance and inhibit the antigen-specific allergic reaction in the intestine. The adduct of MOA has the therapeutic potential for the allergen related immune inflammation.

Topics: Aldehyde Dehydrogenase; Allergens; Animals; Antigens; CD4-Positive T-Lymphocytes; Dendritic Cells; Food Hypersensitivity; Immune Tolerance; Inflammation; Intestines; Measles virus; Mice; Mice, Inbred BALB C; Ovalbumin; Peptides; T-Lymphocytes, Regulatory; Th2 Cells; Transforming Growth Factor beta; Viral Proteins

Approximately 2.5% of young children are allergic to cow milk. In this study, milk protein hydrolysates made from full-cream milk via enzymatic hydrolysis played a positive role in regulating the immune system of ICR mice. Milk protein hydrolysates enhanced immunity in mice by stimulating host immunity, probably by increasing the weight of certain immune system organs, improving the level of hemolysin in serum, and enhancing the phagocytosis of macrophages. Milk protein hydrolysates have the capability to reduce type I hypersensitivity by decreasing IgE levels, IL-4 in serum, and the release of histamine and bicarbonate in peritoneal mast cells, as well as enhancing transforming growth factor-β levels in the serum of ovalbumin-sensitized mice.

Topics: Animals; Dose-Response Relationship, Drug; Female; Food Hypersensitivity; Hydrolysis; Immunity; Immunoglobulin E; Immunoglobulin G; Interleukin-4; Macrophages; Male; Mice; Mice, Inbred ICR; Milk Proteins; Phagocytosis; Spleen; Thymus Gland; Transforming Growth Factor beta

Among food allergies, peanut allergy is frequently associated with severe anaphylactic reactions. In the need for safe and effective therapeutic strategies, probiotics may be considered on the basis of their immunomodulatory properties. The aim of the present study was to investigate the immunological mediators involved in the effects of probiotic VSL#3 oral supplementation on Th2 inflammation and anaphylaxis in a mouse model of peanut allergy.. VSL#3 supplementation to peanut-sensitized mice was effective in ameliorating anaphylaxis and Th2-mediated inflammation, by promoting regulatory responses in the jejunum mucosa and in the mesenteric lymph node, as evaluated by ELISA, real-time PCR, histologic, and immunohistochemical analysis. Probiotic-induced TGF-β mediates its protective effects through the induction of regulatory T cells expressing FOXP3 and/or latency-associated peptide, as proven by in vivo blockade of TGF-β in VSL#3-treated mice with a neutralizing monoclonal antibody one day before challenge.. TGF-β, induced in the gut by VSL#3 supplementation, is capable of reducing the Th2 inflammation associated with food anaphylaxis in a mouse model of peanut sensitization. TGF-β acts through the induction/maintenance of regulatory T cells expressing FOXP3 and/or latency-associated peptide. Probiotics supplementation may represent an effective and safe strategy for treating food allergies in adult population.

Topics: Administration, Oral; Anaphylaxis; Animals; Disease Models, Animal; Female; Food Hypersensitivity; Forkhead Transcription Factors; Inflammation; Intestinal Mucosa; Lymph Nodes; Mice; Mice, Inbred BALB C; Peanut Hypersensitivity; Probiotics; T-Lymphocytes, Regulatory; Transforming Growth Factor beta

B lymphocytes are an important cell population of the immune regulation; their role in the regulation of food allergy has not been fully understood yet.. This study aims to investigate the role of a subpopulation of tolerogenic B cells (TolBC) in the generation of regulatory T cells (Treg) and in the suppression of food allergy-induced intestinal inflammation in mice.. The intestinal mucosa-derived CD5+ CD19+ CX3CR1+ TolBCs were characterized by flow cytometry; a mouse model of intestinal T helper (Th)2 inflammation was established to assess the immune regulatory role of this subpopulation of TolBCs.. A subpopulation of CD5+ CD19+ CX3CR1+ B cells was detected in the mouse intestinal mucosa. The cells also expressed transforming growth factor (TGF)-β and carried integrin alpha v beta 6 (αvβ6). Exposure to recombinant αvβ6 and anti-IgM antibody induced naive B cells to differentiate into the TGF-β-producing TolBCs. Coculturing this subpopulation of TolBCs with Th0 cells generated CD4+ CD25+ Foxp3+ Tregs. Adoptive transfer with the TolBCs markedly suppressed the food allergy-induced intestinal Th2 pattern inflammation in mice.. CD5+ CD19+ CX3CR1+ TolBCs are capable of inducing Tregs in the intestine and suppress food allergy-related Th2 pattern inflammation in mice.

Topics: Adoptive Transfer; Animals; Antigens, Neoplasm; B-Lymphocyte Subsets; CX3C Chemokine Receptor 1; Disease Models, Animal; Enteritis; Food Hypersensitivity; Immune Tolerance; Integrins; Intestinal Mucosa; Lymphocyte Activation; Mice; Receptors, Chemokine; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Th2 Cells; Transforming Growth Factor beta

Food allergies are important etiologic factors in atopic dermatitis. CD19 is a B-cell-specific cell-surface molecule, with a critical role in B-cell activation. Recently, B cells showed independent two subpopulations as CD19(high) and CD19(low). The allergen-specific responses of the CD19(high) and CD19(low) B-cell subpopulations were investigated in patients with non-IgE-mediated food allergy.. Five milk-allergic subjects and eight milk-tolerant subjects were selected by a double-blind placebo-controlled food challenge. Peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with casein or ovalbumin and stained with monoclonal antibodies to distinguish the B-cell subsets.. After allergen stimulation, CD19(high) B cells increased in the number and the fraction in PBMCs in the milk-tolerant group, whereas those remained unchanged in the milk-allergic group. These responses were constant, regardless of the kind of food allergen (milk or egg). The resulting CD19(high)/CD19(low) B-cell ratio increased markedly in the milk-tolerant group after allergen stimulation, but was unchanged in the milk-allergic group. IL-10, IL-17, IL-32 and TGF-β- producing regulatory B cells and Foxp3-expressing regulatory B cells were identified predominantly on CD19 low and CD5(+) B cells.. The response of the CD19(high) B-cell subpopulation to allergen stimulation is decisive for immune tolerance of non-IgE-mediated food allergy in atopic dermatitis. CD19 high and CD5(+) B cells dominantly produce cytokines and express Foxp3. Especially, IL-17 and IL-32 expressing B cells (Br17 & Br32) are present. The exact immunological role of CD19 and cytokines including IL-17 and IL-32 around B cells in immune tolerance requires further investigation.

Topics: Adolescent; Allergens; Animals; Antigens, CD19; B-Lymphocyte Subsets; CD5 Antigens; Dermatitis, Atopic; Double-Blind Method; Eczema; Female; Food Hypersensitivity; Forkhead Transcription Factors; Humans; Immune Tolerance; Immunoglobulin E; Interleukin-10; Interleukin-17; Interleukins; Lymphocyte Activation; Male; Milk; Transforming Growth Factor beta

Regulatory T cells (Tregs) have an essential role in tolerance and immune regulation. However, few and controversial data have been published to date on the role and number of these cells in food allergic children. The forkhead/winged-helix transcription factor box protein 3 (FOXP3) is considered the most reliable marker for Tregs.. This study aims to investigate the FOXP3, interleukin (IL)-10, and transforming growth factor (TGF-β) genes expression in children with IgE-dependent food allergy.. The study group consisted of 54 children with IgE-dependent food allergy (FA) and a control group of 26 non-atopic healthy children. The diagnosis of FA was established using questionnaires, clinical criteria, skin prick tests, serum sIgE antibodies (UniCAP 100 Pharmacia Upjohn), and a double-blind placebo control food challenge. In order to assess gene expression, the isolation of nucleated cells was performed using Histopaque-1077 (Sigma-Aldrich, Germany). The concentration of RNA obtained was measured using a super-sensitive NanoDrop ND1000 spectrophotometer (Thermo Scientific, USA). A reverse transcription reaction was performed using a commercially available set of High Capacity cDNA Archive Kit (Applied Biosystems, USA). Analysis have been carried out in the genetic analyzer 7900HT Real-Time PCR (Applied Biosystems, USA).. The average level of the FOXP3 gene expression in the studied group was 2.19 ± 1.16 and in the control group 2.88 ± 1.66 (p = 0.03). The average level of IL10 mRNA expression in the study group was 13.6 ± 1.07 and was significantly lower than corresponding values in the control group 14.3 ± 1.1 (p = 0.01). There were no significant differences in the average level of the TGF-β mRNA expression in the study group (3.4 ± 0.4) and controls (3.5 ± 0.3; p > 0.05). The FOXP3 gene expression was the highest in children who acquired tolerance to food (3.54 ± 0.75), lower in heated allergen-tolerant children (2.43 ± 0.81), and the lowest in heated allergen-reactive children (1.18 ± 0.5; p = 0.001 control vs heated allergen reactive; p = 0.005 heated allergen tolerant vs heated allergen reactive; p = 0.001 outgrown vs heated allergen reactive). The significant tendency toward lower total IgE levels with a higher FOXP3 mRNA expression was detected (n = 54; Pearson r = -0.4393; p = 0.001).. Children with FA showed statistically significant lower level of the FOXP3 and IL10 gene expression than healthy children. Children acquiring tolerance to the food show significantly higher levels of the FOXP3 gene expression than children with active FA. The correlation between the level of FOXP3 and total IgE was detected.

Topics: Animals; Case-Control Studies; Child; Child, Preschool; Egg Hypersensitivity; Female; Food Hypersensitivity; Forkhead Transcription Factors; Gene Expression Regulation; Humans; Immunoglobulin E; Infant; Interleukin-10; Male; Milk Hypersensitivity; Transforming Growth Factor beta

Food allergy is a disorder in which antigenic food proteins elicit immune responses. Animal models of food allergy have several limitations that influence their utility, including failure to recapitulate several key immunologic hallmarks. Consequently, little is known regarding the pathogenesis and mechanisms leading to food allergy. Staphylococcus aureus-derived enterotoxins, a common cause of food contamination, are associated with antigen responses in atopic dermatitis.. We hypothesized that S aureus-derived enterotoxins might influence the development of food allergy. We examined the influence of administration of staphylococcal enterotoxin B (SEB) with food allergens on immunologic responses and compared these responses with those elicited by a cholera toxin-driven food allergy model.. Oral administration of ovalbumin or whole peanut extract with or without SEB was performed once weekly. After 8 weeks, mice were challenged with oral antigen alone, and the physiologic and immunologic responses to antigen were studied.. SEB administered with antigen resulted in immune responses to the antigen. Responses were highly T(H)2 polarized, and oral challenge with antigen triggered anaphylaxis and local and systemic mast cell degranulation. SEB-driven sensitization induced eosinophilia in the blood and intestinal tissues not observed with cholera toxin sensitization. SEB impaired tolerance specifically by impairing expression of TGF-beta and regulatory T cells, and tolerance was restored with high-dose antigen.. We demonstrate a new model of food allergy to oral antigen in common laboratory strains of mice that recapitulates many features of clinical food allergy that are not seen in other models. We demonstrate that SEB impairs oral tolerance and permits allergic responses.

Topics: Allergens; Anaphylaxis; Animals; Arachis; Cell Degranulation; Disease Models, Animal; Enterotoxins; Eosinophilia; Female; Food Hypersensitivity; Immune Tolerance; Mast Cells; Mice; Mice, Inbred BALB C; T-Lymphocytes, Regulatory; Th2 Cells; Transforming Growth Factor beta

Some epidemiological or association studies suggest that transforming growth factor-beta (TGF-beta) in breast milk may be a decisive factor in diminishing the risk of allergic diseases during infancy. The observations have prompted us to investigate whether TGF-beta, when taken orally, can affect allergic immune responses. Repeated high-dose ovalbumin peptide (OVA) feeding was previously reported to induce OVA-specific IgE production and an anaphylactic reaction after intravenous challenge of OVA in OVA-TCR transgenic mice, which might represent a model for food allergy. By using this model, we showed here that oral administration of high-dose TGF-beta simultaneously with OVA feeding significantly inhibited the OVA-specific IgE elevation and anaphylactic reaction in OVA-TCR transgenic DO11.10 mice. These effects were associated with suppression of OVA-specific IL-4 production and GATA-3 expression and with up-regulation of IFN-gamma production and T-bet expression by splenocytes. Intra-peritoneal injection of anti-TGF-beta-neutralizing antibody abolished the inhibitory effects of orally administered TGF-beta on the serum IgE response and anaphylactic reaction after OVA feeding in DO11.10 mice. Interestingly, oral administration of high-dose TGF-beta suppressed activation-induced T cell death induced by OVA feeding in DO11.10 mice. We thus conclude that TGF-beta, when taken orally at high dose, has the capacity to modulate a food allergy-related reaction, at least in part, through its systemic activity.

Topics: Administration, Oral; Anaphylaxis; Animals; Antigens, Differentiation, T-Lymphocyte; Apoptosis; CD4-Positive T-Lymphocytes; Cytokines; Fas Ligand Protein; Food Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Injections, Subcutaneous; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Transgenic; Ovalbumin; Spleen; T-Lymphocyte Subsets; Transforming Growth Factor beta; Tumor Necrosis Factors

A large body of evidence implicates IgA antibodies in the immune response to pathogens present in the gut. Whether IgA antibodies play a similar role in food allergy remains to be determined.. We sought to characterize beta-lactoglobulin (BLG)-specific serum and secretory IgA antibody production in the gut and to define the role of antigen-induced cytokines in IgA production in a murine model of food allergy.. BLG-specific IgA antibodies were measured in the sera and feces of mice anaphylactic or tolerant to BLG. The number of antibody-secreting cells in the spleen and Peyer's patches was determined by means of ELISPOT. Mesenteric lymph node cells and Peyer's patch T cells were transferred to naive mice, and antibody production in the sera and feces in recipient mice, as well as antibody-secreting cell numbers, were measured.. Serum IgA antibody titers were strongly increased in anaphylactic mice. In contrast, BLG-specific IgA antibody titers were increased in feces but not in sera from tolerant mice. These results were correlated with an increased number of BLG-specific IgA-secreting cells in Peyer's patches from tolerant mice. The adoptive transfer of Peyer's patch CD3+ cells from tolerant mice induced an increased number of IgA-secreting cells preferentially in the Peyer's patches of naive recipient mice. Furthermore, an increase of BLG-induced IL-10 and TGF-beta levels was found at IgA production sites.. These results suggest a role for secretory IgA in tolerance mechanisms to foods. Peyer's patch CD3+ cells are primarily involved by favoring IgA production through the release of IL-10 and TGF-beta.

Topics: Adoptive Transfer; Animals; Disease Models, Animal; Female; Food Hypersensitivity; Immune Tolerance; Immunoglobulin A, Secretory; Interleukin-10; Intestinal Mucosa; Lactoglobulins; Mice; Mice, Inbred C3H; Peyer's Patches; T-Lymphocytes; Transforming Growth Factor beta

Infant food allergies are increasing, and many breast-fed infants now sensitize to maternally-ingested antigens. As low-dose oral tolerance requires generation of suppressor lymphocytes producing TGF-beta1 (Th3 cells), we studied these cells in duodenal biopsies after diagnostic endoscopy. Spontaneous production of Th1, Th2 and Th3 cytokines by duodenal lymphocytes was studied using flow cytometry in 20 children with no eventual clinico-pathological diagnosis (controls), 30 children with multiple food allergy, nine with celiac disease and six with inflammatory enteropathies. Immunohistochemistry and in situ hybridization were used to localize TGF-beta1 protein and mRNA in matched biopsies. We found no significant Th1/Th2 skewing amongst mucosal lymphocytes in allergic children compared to controls, although celiac and inflammatory enteropathy patients showed increased Th1 responses. By contrast, the allergic children showed reduction of TGF-beta1(+) lymphocytes in both epithelial and lamina propria compartments. Reduction of TGF-beta1 expression was also seen in mononuclear cells and epithelium in food allergy by immunohistochemistry and in situ hybridization. The dominant mucosal abnormality in food allergic children was, thus, not Th2 deviation but impaired generation of Th3 cells. As generation of these cells requires innate immune response to enteric bacteria, we suggest that changing infectious exposures may inhibit primary establishment of basic oral tolerance mechanisms.

Topics: Administration, Oral; Antigens; Case-Control Studies; Child; Cytokines; Duodenum; Food Hypersensitivity; Humans; Immune Tolerance; Immunohistochemistry; In Situ Hybridization; In Vitro Techniques; Infant; Infant, Newborn; Intestinal Mucosa; Prospective Studies; RNA, Messenger; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Transforming Growth Factor beta1

TNF-alpha secreted by activated T cells is known to increase intestinal permeability, whereas transforming growth factor (TGF) beta has the ability to protect the epithelial barrier.. We determined the expression of TGF-beta1, its receptors, and TNF-alpha on the mucosa of small intestine to investigate their roles in the pathogenesis of food protein-induced enterocolitis syndrome (FPIES).. Twenty-eight infants diagnosed with FPIES by means of clinical criteria and challenge test results were included. Immunohistochemical stains for TGF-beta1, type 1 and 2 TGF-beta receptors, and TNF-alpha on duodenal biopsy specimens were performed.. TGF-beta1 expression was generally depressed in patients. Expression of type 1 TGF-beta receptor was significantly lower in the patients who had villous atrophy compared with expression in those patients who did not (P <.001) and negatively correlated with the severity of atrophy (r = -0.59, P <.001). Expression of type 2 TGF-beta receptor showed no significant difference between the patients with or without villous atrophy. The immunoreactivity for both TGF-beta receptors on lamina proprial cells was slight or negative. TNF-alpha expression was detected on both epithelial and lamina proprial cells and was significantly greater in the patients who had villous atrophy compared with that in the patients who did not (P <.01).. Our results suggest that decreased countering activity of TGF-beta1 against T-cell cytokines is implicated in the pathogenesis of FPIES. The significantly lower expression of type 1 TGF-beta receptor compared with type 2 receptor suggests the differential contribution of each receptor to the diverse biologic activities of TGF-beta in the intestinal epithelium.

Topics: Activin Receptors, Type I; Duodenum; Enterocolitis; Food Hypersensitivity; Humans; Immunohistochemistry; Infant; Infant, Newborn; Intestinal Mucosa; Milk Proteins; Protein Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type I; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; Soybean Proteins; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Topics: Animals; Breast Feeding; Cattle; Digestive System; Food Hypersensitivity; Humans; Immunity, Maternally-Acquired; Immunoglobulin G; Infant Food; Infant, Newborn; Milk Proteins; Milk, Human; Transforming Growth Factor beta