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
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Wilhelm, Christoph; Harrison, Oliver J; Schmitt, Vanessa et al. (2016) Critical role of fatty acid metabolism in ILC2-mediated barrier protection during malnutrition and helminth infection. J Exp Med 213:1409-18
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
Mortha, Arthur; Chudnovskiy, Aleksey; Hashimoto, Daigo et al. (2014) Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343:1249288
Schiering, Chris; Krausgruber, Thomas; Chomka, Agnieszka et al. (2014) The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature :
Klebanoff, Christopher A; Spencer, Sean P; Torabi-Parizi, Parizad et al. (2013) Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells. J Exp Med 210:1961-76
Belkaid, Yasmine; Grainger, John (2013) Immunology. Mucus coat, a dress code for tolerance. Science 342:432-3
Klatt, N R; Estes, J D; Sun, X et al. (2012) Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with mucosal damage in SIV infection. Mucosal Immunol 5:646-57
Grainger, John R; Hall, Jason A; Bouladoux, Nicolas et al. (2010) Microbe-dendritic cell dialog controls regulatory T-cell fate. Immunol Rev 234:305-16
Belkaid, Y; Liesenfeld, O; Maizels, R M (2010) 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: induction and control of regulatory T cells in the gastrointestinal tract: consequences for local and peripheral immune responses. Clin Exp Immunol 160:35-41
Hand, Timothy; Belkaid, Yasmine (2010) Microbial control of regulatory and effector T cell responses in the gut. Curr Opin Immunol 22:63-72

Showing the most recent 10 out of 11 publications