Retinoic acid can exacerbate T cell intrinsic TLR2 activation to promote tolerance

PLoS One. 2015 Mar 31;10(3):e0118875. doi: 10.1371/journal.pone.0118875. eCollection 2015.


The contribution of vitamin A to immune health has been well established. However, recent evidence indicates that its active metabolite, retinoic acid (RA), has the ability to promote both tolerogenic and inflammatory responses. While the outcome of RA-mediated immunity is dependent upon the immunological status of the tissue, the contribution of specific innate signals influencing this response have yet to be delineated. Here, we found that treatment with RA can dampen inflammation during intestinal injury. Importantly, we report a novel and unexpected requirement for TLR2 in RA-mediated suppression. Our data demonstrate that RA treatment enhances TLR2-dependent IL-10 production from T cells and this, in turn, potentiates T regulatory cell (TREG) generation without the need for activation of antigen presenting cells. These data also suggest that combinatorial therapy using RA and TLR2 ligands may be advantageous in the design of therapies to treat autoimmune or inflammatory disease.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Colitis / chemically induced
  • Colitis / immunology
  • Colitis / metabolism
  • Colitis / pathology
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Immune Tolerance*
  • Immunophenotyping
  • Inflammation Mediators / metabolism
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Lymphocyte Activation
  • Mice
  • Signal Transduction
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Toll-Like Receptor 2 / metabolism*
  • Tretinoin / metabolism*
  • Tretinoin / pharmacology
  • Vitamin A / metabolism


  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • Toll-Like Receptor 2
  • Vitamin A
  • Tretinoin