Using complementary approaches of vitamin A deficiency and mice for which response to the vitamin A metabolite RA, was abrogated in T cells, we identified a previously unrecognized role for retinoic acid and its receptor, retinoic acid receptor alpha, in the regulation of early T cell activation events and T cell polarization. Impaired response of T cells to the vitamin A metabolite RA was associated with defect in protective immunity to mucosal infection and altered response to oral vaccine. Our work also demonstrates that the vitamin A metabolite, RA, plays a role in the control of dendritic cells function and development. Notably, we found that RA regulates pre-cDC differentiation and that vitamin A deficiency has major consequences on the development of mucosal dendritic cells.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2013
Total Cost
$220,562
Indirect Cost
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Mortha, Arthur; Chudnovskiy, Aleksey; Hashimoto, Daigo et al. (2014) Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343:1249288
Spencer, S P; Wilhelm, C; Yang, Q et al. (2014) Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity. Science 343:432-7