PURPOSE: 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.
PURPOSE: 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: Daniel J Cua; Jonathan Sherlock; Yi Chen; Craig A Murphy; Barbara Joyce; Brian Seymour; Linda Lucian; Wayne To; Sylvia Kwan; Tatyana Churakova; Sandra Zurawski; Maria Wiekowski; Sergio A Lira; Daniel Gorman; Robert A Kastelein; Jonathon D Sedgwick Journal: Nature Date: 2003-02-13 Impact factor: 49.962
Authors: Sergei Kusmartsev; Fengdong Cheng; Bin Yu; Yulia Nefedova; Eduardo Sotomayor; Richard Lush; Dmitry Gabrilovich Journal: Cancer Res Date: 2003-08-01 Impact factor: 12.701