title: Retinoic acid inhibits CD25+ dendritic cell expansion and γδ T-cell activation in experimental autoimmune uveitis.
abstract: OBJECTIVE
  We determined the mechanism by which all-trans retinoic acid (ATRA) inhibits experimental autoimmune uveitis (EAU) and determined the role of γδ T cells in this autoimmune disease.
  
  
  METHODS
  C57BL/6 (B6) mice were immunized with the uveitogenic, interphotoreceptor retinoid-binding protein1-20 peptide (IRBP1-20) in complete Freund's adjuvant (CFA), with or without a preceding ATRA treatment. Responses and pathogenic activity of Th1- and Th17-autoreactive T cells were compared, and the effects of ATRA on γδ T cells and CD25(+) dendritic cell (DC) subset were determined. Interactions among uveitogenic T cells, DC subsets, and γδ T cells were investigated.
  
  
  RESULTS
  Administration of ATRA to B6 mice in which EAU was induced suppressed the response of Th17 autoreactive T cells, which was associated with decreased generation of the CD25(+) DC subset and suppressed activation of γδ T cells. Adoptively transferred γδ T cells isolated from ATRA-treated mice showed a diminished ability to promote the activation of Th17 autoreactive T cells in vitro and in vivo compared to γδ T cells from untreated donors.
  
  
  CONCLUSIONS
  ATRA inhibits the expansion of CD25(+) DCs and γδ T-cell activation, thereby restraining the Th17 autoreactive T-cell response.
authors.affiliation: Doheny Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Dongchun
authors.initials: D
authors.lastname: Liang
authors.forename: Aijun
authors.initials: A
authors.lastname: Zuo
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
authors.forename: Willi K
authors.initials: WK
authors.lastname: Born
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: O'Brien
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.forename: Deming
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; C098680:Il17a protein, mouse; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014212:Tretinoin
keywords: EAU; Th17; autoimmunity; interleukin-17; retinoid acid; uveitis; γδ T cell