In an ovalbumin-induced murine food allergy model,[21] we found that activated T cells migrate into the colon, where they produced large amounts of Th2 cytokines such as selleck products interleukin (IL)-4 and IL-5. Our subsequent study has demonstrated that trafficking of pathogenic T cells from the systemic compartments into the colon is mediated by S1P; thus, infiltration of activated T cells into the colon of allergic mice is inhibited by treatment with FTY720 (Fig. 1).[22] In addition, infiltration or proliferation of mast cells,

effector cells in the development of food allergy, in the colon is prevented by treatment with FTY720 (Fig. 1).[22] Similar effects of FTY720 on trafficking of pathogenic cells in the development of intestinal inflammation have been reported in some experimental intestinal inflammation models (e.g. IL-10-deficient mice, dextran sulphate sodium treatment, and T cell transfer models).[23-25] Collectively, these findings suggest

that in addition to the physiological role of S1P–S1P1 axis in the optimal supplementation of immunocompetent cells to the intestine, it also participates mainly in the development of intestinal immune diseases (e.g. allergy and inflammation) at the stage of pathogenic cell trafficking into the colon, which is a potential target for prevention and treatment of these intestinal immune diseases. Vitamins are organic compounds that we cannot synthesize in sufficient quantities, and that therefore need selleck chemicals llc to be supplied from the diet or commensal bacteria. Some of these vitamins are water-soluble (e.g. vitamin B family and vitamin C) whereas others are hydrophobic (e.g. vitamins A, D, E, and K). Both hydrophilic and hydrophobic vitamins and their metabolites have diverse functions in many biological events, including immunological regulation (Fig. 2).

Indeed, vitamin deficiency results in high susceptibility to infection and immune diseases.[26] Accumulating evidence has revealed the molecular and cellular mechanisms of vitamins underlying regulation of the immune system. The biggest breakthrough was the discovery of the function of vitamin A in regulating the tissue-tropism of lymphocytes activated in the gut (reviewed in Reference[27]). O-methylated flavonoid Vitamin A is obtained from the diet as all-trans-retinol, retinyl esters, or β-carotene and is metabolized into retinol or retinoic acid (RA) in the tissues.[28] Immunologically, RA induces the expression of α4β7 integrin and the chemokine receptor CCR9 on both T and B cells.[29, 30] Because both α4β7 integrin and CCR9 are key molecules in lymphocyte homing into the gut, activated lymphocytes in the presence of RA tend to traffic into the intestinal lamina propria (Fig. 2). In agreement with this, vitamin A-deficient mice show a lack of T cells and IgA PCs in the intestine.[29, 30] RA plays an important role in determining not only the gut-tropism of lymphocytes activated in the intestine but also T cell differentiation.