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Dongchun Liang, Aijun Zuo, Hui Shao, Willi K. Born, Rebecca L. O'Brien, Henry J. Kaplan, Deming Sun; Retinoic Acid Inhibits CD25+ Dendritic Cell Expansion and γδ T-Cell Activation in Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2013;54(5):3493-3503. doi: 10.1167/iovs.12-11432.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
ATRA inhibits the expansion of CD25+ DCs and γδ T-cell activation, thereby restraining the Th17 autoreactive T-cell response.
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