sphingosine-1-phosphate and Food-Hypersensitivity

The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases.

Topics: Food; Food Hypersensitivity; Gastrointestinal Tract; Homeostasis; Humans; Inflammatory Bowel Diseases; Lipids; Lysophospholipids; Nucleotides; Nutritional Physiological Phenomena; Sphingosine; Vitamins

It has been shown that dietary materials are involved in immune regulation in the intestine. Lipids mediate immune regulation through a complex metabolic network that produces many kinds of lipid mediators. Sphingosine-1-phosphate (S1P) is a lipid mediator that controls cell trafficking and activation. In this review, we focus on the immunological functions of S1P in the regulation of intestinal immune responses such as immunoglobulin A production and unique T cell trafficking, and its role in the development of intestinal immune diseases such as food allergies and intestinal inflammation, and also discuss the relationship between dietary materials and S1P metabolism.

Topics: Animals; Diet; Food; Food Hypersensitivity; Humans; Immunoglobulin A; Intestinal Diseases; Intestines; Lysophospholipids; Mice; Rats; Sphingosine; T-Lymphocytes

Anaphylaxis is the most concerning manifestation of hypersensitivity. Recent thorough investigations on the pathophysiology of anaphylaxis achieved important advances in its understanding, regarding in particular the emerging role of mediators such as platelet activating factor (PAF) and sphyngosine 1 phosphate (S1P) and the improved knowledge on the actors of the signaling cascade, from the contact between the specific allergen and the IgE fixed on the Fc-epsilon-RI receptor to the opening of calcium channels. These advances may provide new diagnostic and therapeutical tools. In particular, a role for PAF and S1P as laboratory markers of anaphylaxis is likely to be developed, and innovative preventive strategies able to induce a negative signaling are currently under evaluation. Also, using well known preventive treatments, such as allergen specific immunotherapy may offer new perspectives for the management of patients at risk of potentially fatal reaction to foods. In fact, controlled studies demonstrated that sublingual immunotherapy is able to significantly increase the tolerance to the causative foods, fulfilling the need and protecting the allergic subject from anaphylaxis caused by accidental ingestion of small food amounts. The article also presented some promising patents on anaphylaxis.

Topics: Anaphylaxis; Animals; Food Hypersensitivity; Humans; Immunotherapy; Lysophospholipids; Patents as Topic; Platelet Activating Factor; Signal Transduction; Sphingosine

Sphingosine 1-phosphate (S1P) has been proposed as a regulator of lymphocyte trafficking, but its role in mucosa-associated diseases, such as in food allergies, remains to be elucidated. To examine the role of S1P in allergic diseases in the intestine, we used a Th2 cell-mediated Ag-specific allergic diarrhea model and demonstrated that type 1 S1P receptor (S1P(1)) expression was preferentially associated with pathogenic CD4(+) T cells for the development of allergic reactions. Consistent with this demonstration, treatment with FTY720, a modulator of the S1P(1), prevented allergic diarrhea by inhibiting the migration of systemically primed pathogenic CD4(+) T cells induced by oral challenge with allergen into the large intestine. In addition, FTY720 hampered mast cell infiltration into the large intestine, whereas eosinophil infiltration into the large intestine and total and allergen-specific serum IgE production were comparable between mock- and FTY720-treated groups. These results suggest that modulation of the S1P-mediated pathway to inhibit the migration of pathogenic CD4(+) T cells and mast cells into the large intestine could be a novel strategy for preventing allergic diarrhea.

Topics: Animals; CD4-Positive T-Lymphocytes; Cell Migration Inhibition; Cells, Cultured; Chemotaxis, Leukocyte; Diarrhea; Epitopes, T-Lymphocyte; Female; Fingolimod Hydrochloride; Food Hypersensitivity; Immunosuppressive Agents; Intestine, Large; Lysophospholipids; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Propylene Glycols; Sphingosine; Spleen; Th2 Cells