Retinoic acid, the active metabolite of vitamin A, is implicated in a broad range of well-studied pre- and post-natal functions. By comparison, its involvement in the development and function of the immune system remains largely unknown. However, it has recently been shown that retinoic acid has a protective effect in a murine model of colitis by switching the cytokine production by γδ T cells from pro- (IL-17A) to anti-inflammatory (IL-22). At the border between innate and adaptive immunity, γδ T cells constitute an important part of the immune system and are highly involved in the pathogenesis of several autoimmune or infectious disorders. Although these cells are found throughout the immune system, they can be divided into subpopulations which are interestingly enhanced in the compartments located at environmental interfaces such as the skin, intestine, uterus and lungs. Throughout this fellowship, I propose to (1) study the molecular mechanisms by which retinoic acid is able to change the fate of γδ T cells, (2) analyze the differential impact of retinoic acid between the γδ T cell subtypes, and (3) study the influence of retinoic acid in vivo, in two different autoimmune disorders, psoriasis and experimental autoimmune encephalomyelitis. This study will highlight γδ T cells as new therapeutic targets and retinoids as immunomodulators for the development of efficient immunotherapies, a highly promising challenge in medical research for the future treatment of cancers, autoimmune and infectious disorders.
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