title: Retinoic acid can exacerbate T cell intrinsic TLR2 activation to promote tolerance.
abstract: 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.
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Children's Hospital of Los Angeles, Los Angeles, California, United States of America.
authors.forename: Vivien
authors.initials: V
authors.lastname: Nguyen
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine and University of Southern California, Los Angeles, California, United States of America.
authors.forename: Kandyce
authors.initials: K
authors.lastname: Pearson
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine and University of Southern California, Los Angeles, California, United States of America.
authors.forename: Jee-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine and University of Southern California, Los Angeles, California, United States of America.
authors.forename: Karishma
authors.initials: K
authors.lastname: Kamdar
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine and University of Southern California, Los Angeles, California, United States of America.
authors.forename: R William
authors.initials: RW
authors.lastname: DePaolo
mesh_terms: D000818:Animals; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D007108:Immune Tolerance; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D014801:Vitamin A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D051195:Toll-Like Receptor 2; D014801:Vitamin A; D014212:Tretinoin
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