Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001133-04
Application #
8745556
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2013
Total Cost
$220,562
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Mao, Kairui; Baptista, Antonio P; Tamoutounour, Samira et al. (2018) Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism. Nature 554:255-259
Ridaura, Vanessa K; Bouladoux, Nicolas; Claesen, Jan et al. (2018) Contextual control of skin immunity and inflammation by Corynebacterium. J Exp Med 215:785-799
Jijon, H B; Suarez-Lopez, L; Diaz, O E et al. (2018) Intestinal epithelial cell-specific RAR? depletion results in aberrant epithelial cell homeostasis and underdeveloped immune system. Mucosal Immunol 11:703-715
Buxbaum, Nataliya P; Farthing, Donald E; Maglakelidze, Natella et al. (2017) In vivo kinetics and nonradioactive imaging of rapidly proliferating cells in graft-versus-host disease. JCI Insight 2:
Dutzan, Nicolas; Abusleme, Loreto; Bridgeman, Hayley et al. (2017) On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier. Immunity 46:133-147
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
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
Schiering, Chris; Krausgruber, Thomas; Chomka, Agnieszka et al. (2014) The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature 513:564-8
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

Showing the most recent 10 out of 17 publications