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Qihua Le, Xin Wang, Wentao Wang, JianJiang Xu; ATRA attenuates corneal graft rejection by increasing regulatory T cell and suppressing Th17 cell in the presence of TGF-β. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3214.
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To explore the effect of all-trans retinoid acid (ATRA) on regulatory T cell-T helper 17 cell (Treg-Th17) balance in recipient mice after allogenic penetrating keratoplasty, and analyze its correlation with the graft survival.
Allogenic corneal transplantation was performed using C57/BL6 mice as donors and Balb/c mice as recipients. ATRA, TGF-β, ATRA+TGF-β (mixed group), and control solution was administered to recipient mice for 8 weeks after surgery. The graft status was assessed twice per week. The percentage of CD4+CD25+Foxp3+Tregs and Th17 in the peripheral blood, spleen, and draining lymph nodes was analyzed. The expression of Foxp3, RORγt and RORα mRNA in grafts was tested, and the concentration of IL-10 and IL-17 in serum and aqueous humor was measured. The suppressive activity of Tregs isolated from recipients was determined. One-way analysis of variance and Pearson correlation analysis were used to compare the results.
Mixed treatment of ATRA and TGF-β significantly promoted graft survival. Moreover, with the presence of TGF-β, ATRA upregulated CD4+CD25+Foxp3+Treg cells and suppressed Th17 cells in the blood, spleen and draining lymph nodes of recipient mice, as well as enhanced Foxp3 expression and inhibited RORγt expression in grafts and PBMCs. Simultaneously, increased Foxp3+ cells and decreased IL-17+ cells in conjunctiva were found in recipients with mixed treatment, along with reduced IL-17 level in serum and aqueous humor, and increased IL-10 level in aqueous humor. Moreover, Tregs isolated from recipient mice with mixed treatment presented the strongest suppressive activity.
Combined application of ATRA and TGF-β may shift Th17-Treg balance towards Tregs, hence facilitating the induction of immunological tolerance after allogenic corneal transplantation and representing a potential therapeutic approach in the treatment for posttransplant rejection.
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