CD86
CD80
葡萄膜炎
免疫学
流式细胞术
免疫印迹
T细胞
主要组织相容性复合体
抗原
体外
化学
分子生物学
医学
生物
细胞毒性T细胞
CD40
免疫系统
生物化学
基因
作者
Juan Yun,Tong Xiao,Lanlan Zhou,Roger W. Beuerman,Juanjuan Li,Yuan Zhao,Amir Hadayer,Xiao Min Zhang,Deming Sun,Henry J. Kaplan,Hui Shao
标识
DOI:10.1167/iovs.17-23127
摘要
Purpose: To investigate the role of damage-associated molecular patterns (DAMPs) in recurrent experimental autoimmune uveitis (EAU). Methods: Recurrent EAU was induced in Lewis rats by interphotoreceptor retinoid-binding protein (IRBP) R16-peptide specific T cells (tEAU). Aqueous humor and serum samples were kinetically collected and DAMPs examined by quantitative proteomics, Western blot analysis, and ELISA. tEAU rats were treated with S100 inhibitor paquinimod followed by disease evaluation. The functions of T effector cells and T regulatory cells (Tregs) were compared between treated and nontreated groups. The expression of costimulatory molecules on antigen-presenting cells was examined by flow cytometry. Results: S100A8, but not high mobility group box 1 (HMGB1), in the eye was found to be correlated with intraocular inflammatory episodes. Administration of paquinimod significantly protected tEAU rats from recurrence. Treated tEAU rats had fewer R16-specific Th1 and Th17 cells, but increased numbers of Tregs. R16-specific T cells from treated tEAU rats into naïve recipients prevented induction of tEAU by R16-specific T cells from nontreated tEAU rats. Moreover, APCs from treated tEAU rats expressed higher levels of a negative costimulatory molecule, CD200R, and lower levels of CD80, CD86, and MHC class II molecules compared to APCs from nontreated tEAU rats. An opposite pattern of expression of these molecules was observed on APCs incubated in vitro with recombinant S100A8. Conclusions: Our data demonstrate a link between local expression of DAMPs and autoimmune responses, and suggest that complete S100A8/A9 blockade may be a new therapeutic target in recurrent autoimmune uveitis.
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