tretinoin and Intestinal-Diseases

As one of the most important metabolites of vitamin A, all-trans retinoic acid (RA) plays a crucial role in regulating immune responses. RA has been shown to promote the differentiation of naïve T and B cells and perform diverse functions in the presence of different cytokines. RA also induces gut tropic lymphocytes through upregulating the expression of chemokine (C-C motif) receptor 9 (CCR9) and α4β7 integrin. In addition, RA promotes the expression of the enzyme retinal dehydrogenase (RALDH) on dendritic cells, which in turn strengthens the ability to synthesize RA. Due to the insolubility of RA, proper formulation design can maximize its ability to improve immune responses for vaccines. Recent studies have developed some formulations co-loading RA and antigen, which can effectively imprint lymphocytes gut homing properties and induce intestine immune responses as well as systemic responses through parenteral administration, providing a promising direction for the protection against mucosal infections. Here, we review the mechanism and effects of RA on lymphocyte differentiation and gut homing, and recent progress of RA delivery systems to improve mucosal immune responses.

Topics: Adjuvants, Immunologic; Animals; B-Lymphocytes; Cell Differentiation; Dendritic Cells; Disease Models, Animal; Drug Carriers; Drug Compounding; Humans; Immunity, Mucosal; Immunogenicity, Vaccine; Intestinal Diseases; Intestinal Mucosa; Mice; Solubility; T-Lymphocytes; Tretinoin; Vaccine Excipients; Vaccines

Retinoic acid or vitamin A is important for an extensive range of biological processes, including immunomodulatory functions, however, its role in gastrointestinal parasite infections is not yet clear. Despite this, parasite infected individuals are often supplemented with vitamin A, given the co-localised prevalence of parasitic infections and vitamin deficiencies. Therefore, it is important to understand the impact of this vitamin on the immune responses to gastrointestinal parasites. Here, we review data regarding the role of retinoic acid signalling in mouse models of intestinal nematode infection, with a view to understanding better the practice of giving vitamin A supplements to worm-infected people.

Topics: Animals; Disease Models, Animal; Helminthiasis; Intestinal Diseases; Intestinal Diseases, Parasitic; Mice; Nematode Infections; Signal Transduction; Tretinoin

Interactions between the microbiota and mammalian host are essential for defense against infection, but the microbial-derived cues that mediate this relationship remain unclear. Here, we find that intestinal epithelial cell (IEC)-associated commensal bacteria, segmented filamentous bacteria (SFB), promote early protection against the pathogen Citrobacter rodentium, independent of CD4

Topics: Animals; Bacillus cereus; Bacteria; Bifidobacterium bifidum; CD4-Positive T-Lymphocytes; Citrobacter rodentium; Epithelial Cells; Histone Code; Host Microbial Interactions; Intestinal Diseases; Male; Mice; Mice, Inbred C57BL; Microbiota; Nitric Oxide; Signal Transduction; Symbiosis; Tretinoin

The ectonucleotidases CD39 and CD73 sequentially degrade the extracellular ATP pool and release immunosuppressive adenosine, thereby regulating inflammatory responses. This control is likely to be critical in the gastrointestinal tract where high levels of ATP are released in particular by commensal bacteria. The aim of this study was therefore to evaluate the involvement of the adenosinergic regulation in the intestine of mice in steady-state conditions and on acute infection with Toxoplasma gondii. We show that both conventional (Tconv) and regulatory (Treg) CD4(+) T lymphocytes express CD39 and CD73 in the intestine of naive mice. CD73 expression was downregulated during acute infection with T. gondii, leading to impaired capacity to produce adenosine. Interestingly, the expression of adenosine receptors was maintained and treatment with receptor agonists limited immunopathology and dysbiosis, suggesting that the activation of adenosine receptors may constitute an efficient approach to control intestinal inflammation associated with decreased ectonucleotidase expression.

Topics: 5'-Nucleotidase; Adenosine; Animals; Antigens, CD; Apyrase; Disease Models, Animal; Gene Expression; Gene Expression Regulation; Intestinal Diseases; Mice; Mice, Knockout; Receptor, Adenosine A2A; Receptor, Adenosine A2B; T-Lymphocyte Subsets; Toxoplasma; Transforming Growth Factor beta; Tretinoin