Abstract

Using complementary approaches of micronutrient deficiencies and mice for which responses to defined micronutrients was abrogated in T cells or antigen presenting cells, we identified a previously unrecognized role for retinoic acid and its receptor, retinoic acid receptor alpha in the control of T cell and 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. Our work further explored how the immune system adapts to various states of malnutrition and demonstrated that defined aspect of innate immunity could be metabolicaly boosted to compensate for defective adaptive immunity under these settings. We also developed novel models of nutrient deficiency and integrated the exploration of the microbiota to these questions.

  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 #
1ZIAAI001133-08
Application #
9566725
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
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  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