Modulation of T cell and innate immune responses by retinoic Acid

J Immunol. 2014 Apr 1;192(7):2953-8. doi: 10.4049/jimmunol.1303245.

Abstract

Retinoic acid (RA) is produced by a number of cell types, including macrophages and dendritic cells, which express retinal dehydrogenases that convert vitamin A to its main biologically active metabolite, all-trans RA. All-trans RA binds to its nuclear retinoic acid receptors that are expressed in lymphoid cells and act as transcription factors to regulate cell homing and differentiation. RA production by CD103(+) dendritic cells and alveolar macrophages functions with TGF-β to promote conversion of naive T cells into Foxp3(+) regulatory T cells and, thereby, maintain mucosal tolerance. Furthermore, RA inhibits the differentiation of naive T cells into Th17 cells. However, Th1 and Th17 responses are constrained during vitamin A deficiency and in nuclear RA receptor α-defective mice. Furthermore, RA promotes effector T cell responses during infection or autoimmune diseases. Thus, RA plays a role in immune homeostasis in the steady-state but activates pathogenic T cells in conditions of inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Immunity, Innate / immunology*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Models, Immunological
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Tretinoin / immunology*
  • Tretinoin / metabolism
  • Tretinoin / pharmacology

Substances

  • Tretinoin