Retinoic Acid and Retinoic Acid Receptors as Pleiotropic Modulators of the Immune System

Annu Rev Immunol. 2016 May 20;34:369-94. doi: 10.1146/annurev-immunol-041015-055427.


Vitamin A is a multifunctional vitamin implicated in a wide range of biological processes. Its control over the immune system and functions are perhaps the most pleiotropic not only for development but also for the functional fate of almost every cell involved in protective or regulatory adaptive or innate immunity. This is especially key at the intestinal border, where dietary vitamin A is first absorbed. Most effects of vitamin A are exerted by its metabolite, retinoic acid (RA), which through ligation of nuclear receptors controls transcriptional expression of RA target genes. In addition to this canonical function, RA and RA receptors (RARs), either as ligand-receptor or separately, play extranuclear, nongenomic roles that greatly expand the multiple mechanisms employed for their numerous and paradoxical functions that ultimately link environmental sensing with immune cell fate. This review discusses RA and RARs and their complex roles in innate and adaptive immunity.

Keywords: adaptive immunity; gene expression; genomic; innate immunity; nongenomic; vitamin A.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity
  • Animals
  • Humans
  • Immune System*
  • Immunity, Innate
  • Immunomodulation
  • Intestinal Mucosa / physiology*
  • Receptors, Retinoic Acid / immunology*
  • Receptors, Retinoic Acid / metabolism
  • Tretinoin / immunology
  • Tretinoin / metabolism*
  • Vitamin A / immunology*


  • Receptors, Retinoic Acid
  • Vitamin A
  • Tretinoin