title: Seeing through the dark: New insights into the immune regulatory functions of vitamin A.
abstract: The importance of vitamin A for host defense is undeniable and the study of its mechanisms is paramount. Of the estimated 250 million preschool children who are vitamin A-deficient (VAD), 10% will die from their increased susceptibility to infectious disease. Vitamin A supplementation was established in the 1980s as one of the most successful interventions in the developing world. Understanding how vitamin A controls immunity will help curb the mortality and morbidity associated with vitamin A deficiency and exploit the immune-enhancing capacity of vitamin A to heighten host resistance to infectious disease. The discoveries that retinoic acid (RA) imprints the homing of leukocytes to the gut and enhances the induction of regulatory T cells, highlighted a potential role for RA in mucosal tolerance. However, more recently emerging data tell of a more profound systemic impact of RA on leukocyte function and commitment. In animal models using genetic manipulation of RA signaling, we learned when and how RA controls T cell fate. Here, we review the role for RA as a critical checkpoint regulator in the differentiation of CD4(+) T cells within the immune system.
authors: Division of Transplantation Immunology and Mucosal Biology, Kings College London, United Kingdom.
authors: Chrysothemis C
authors: CC
authors: Brown
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, NH, USA.
authors: Randolph J
authors: RJ
authors: Noelle
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy; D051379:Mice; D018448:Models, Immunological; D012176:Retinoids / Q000627:therapeutic use; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014212:Tretinoin / Q000276:immunology / Q000378:metabolism; D014801:Vitamin A / Q000276:immunology*; D014802:Vitamin A Deficiency / Q000276:immunology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007166:Immunosuppressive Agents; D012176:Retinoids; D014801:Vitamin A; D014212:Tretinoin
keywords: CD4+ T cells; Dendritic cells; Gut immunity; Innate lymphoid cells; Retinoic acid; T-cell polarization; Vitamin A metabolism