Large either placebo controlled studies in vitamin deficient populations in developing countries show that vitamin A supplementation is associated with decreased childhood mortality from diarrheal disease and measles, underscoring the critical role for vitamin A in immunity. Studies on vitamin A deficiency Inhibitors,Modulators,Libraries have consistently de monstrated an indispensable role for vitamin A in main taining host immunity to a variety of pathogens. Retinoic acid is the bioactive form of vitamin A. all trans retinoic acid is the most abundant form of RA found in the circulation. RA influences immunity via multiple mechanisms. CD4 T cells are the immune component most prominently affected by RA. RA augments the differentiation of inducible T regulatory cells, which is abrogated both in vitro and in vivo in either vitamin A deficiency Inhibitors,Modulators,Libraries states or using ret inoic acid receptor deficient mice.

In vitamin A deficient mice, RA restores CD4 T cell mediated im munity, homeostasis, and activation. Previous in vestigations suggest that retinoic acid receptor alpha mediates these RA induced effects on T cells. ATRA Inhibitors,Modulators,Libraries exerts its bioactivity via binding to retinoic acid receptor ligand activated transcription factors, and ATRA is a high affinity ligand for retinoic acid receptor alpha. ATRA binding to RAR monomers then induces hetero dimerization with retinoid X receptors. The RAR RXR complex in turn binds to retinoic acid response elements which are present in the promoters of RA responsive genes and result in gene activation. Th2 cells were initially characterized as expressing IL 4, IL 5, and IL 13.

IL 4 is the major factor dri ving Th2 differentiation, IgE class switching, and alterna tive macrophage activation, whereas IL 13 functions as an effector Inhibitors,Modulators,Libraries molecule that mediates eosinophilic inflam mation, airway hyper responsiveness, and mucus secre tion. IL 5 is the major eosinophil active Inhibitors,Modulators,Libraries cytokine and induces eosinophilopoiesis and eosinophil release from the bone marrow, enhances eosinophil survival, and acts as a costimulator for eosinophil activation. In vivo, vitamin A is associated with eosinophilic tissue inflammation, which is both a protective component of anti helminth immunity and a major contributor to asthma pathogenesis. Vitamin A deficiency inhibits para site expulsion due to reduced eosinophilia and IL 5 secretion by antigen specific lymphocytes in vivo, and vitamin A supplementation restores parasite immunity.

Vitamin A deficiency diminishes and high selleck inhibitor level vitamin A supplementation restores Th2 cytokines and eosinophilia induced by experimental asthma. RAR agonists and RAR antagonists exert opposite effects on the production of Th2 cytokines by in vitro stimulated T cells. We have recently characterized two major subpopulations within the Th2 lineage IL 5 Th2, which express IL 5, IL 4, and IL 13, and IL 5 Th2 cells, which only express the latter two cytokines.