Regulatory role of TLR ligands on the activation of autoreactive T cells by retinal astrocytes.
Regulatory role of TLR ligands on the activation of autoreactive T cells by retinal astrocytes.
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DOI：
10.1167/iovs.08-3303
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发表时间：
2009-10
影响因子：
4.4
通讯作者：
Shao H
中科院分区：
文献类型：
--
作者：
Jiang G;Ke Y;Sun D;Wang Y;Kaplan HJ;Shao H
确定 Toll 样受体 (TLR) 配体是否调节视网膜星形胶质细胞 (RAC) 的激活以及 RAC 在光感受器间视黄醇结合蛋白 (IRBP) 特异性 T 细胞极化中的可能作用。使用实时 PCR 和流式细胞术检查从 C57BL/6 小鼠分离的 RAC 上的 TLR 表达。通过测量主要组织相容性复合物 II 类和共刺激分子的表达以及细胞因子的产生来评估 TLR 配体治疗前后 RAC 与 T 细胞相互作用的能力。通过 T 细胞增殖、细胞因子产生和疾病诱导能力来检查 RAC（有或没有 TLR 刺激）对应答者 IRBP 特异性 T 细胞的刺激作用。培养的小鼠 RAC 表达 TLR2、TLR3 和 TLR4。不同的TLR配体对RAC有不同的刺激作用。 PolyI:C（TLR3 配体）在刺激 RAC 获得抗原呈递功能方面效果最大，而 BLP（TLR2 配体）效果最低。 TLR3 连接增加了 MHC 和共刺激分子的表达，并诱导 RAC 产生 IL-6、IL-12 和 IL-23。经过聚 I:C 处理的 RAC 激活的 IRBP 特异性 T 细胞会剧烈扩增，产生大量的 IFN-γ 和 IL-17，并在注射到初始小鼠体内时诱导实验性自身免疫性葡萄膜炎。 RAC 对自身反应性 T 细胞的刺激作用由 TLR 配体调节。 TLR3 对 RAC 促进 Th1 和 Th17 IRBP 特异性 T 细胞激活的能力有显着影响。因此，接触微生物抗原可能会促进自身反应性 T 细胞的激活，从而改变对自身免疫性葡萄膜炎的易感性。
To determine whether Toll-like receptor (TLR) ligands regulate the activation of retinal astrocytes (RACs) and the possible role of RACs in the polarization of interphotoreceptor retinoid-binding protein (IRBP)-specific T cells. TLR expression on RACs isolated from C57BL/6 mice was examined using real-time PCR and flow cytometry. The ability of RACs before or after treatment with TLR ligands to interact with T cells was assessed by measuring major histocompatibility complex class II and costimulatory molecule expression and cytokine production. The stimulatory effect of RACs, with or without TLR stimulation, on responder IRBP-specific T cells was examined by T-cell proliferation, cytokine production, and disease-inducing ability. Cultured mouse RACs expressed TLR2, TLR3, and TLR4. Different TLR ligands had distinct stimulatory effects on RACs. PolyI:C (a TLR3 ligand) had the greatest effect in stimulating RACs to acquire antigen-presentation function, whereas BLP (a TLR2 ligand) had the lowest effect. TLR3 ligation increased the expression of MHC and costimulatory molecules and induced the production of IL-6, IL-12, and IL-23 by RACs. IRBP-specific T cells activated by polyI:C-treated RACs expanded vigorously, produced significant amounts of IFN-γ and IL-17, and induced experimental autoimmune uveitis when injected into naive mice. The stimulatory effect of RACs on autoreactive T cells is regulated by TLR ligands. TLR3 had a marked effect on the ability of RACs to promote the activation of Th1 and Th17 IRBP-specific T cells. Thus, exposure to microbial antigen(s) may alter susceptibility to autoimmune uveitis by promoting the activation of autoreactive T cells.
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I型Interferon自分泌 - 核酸环与树突状细胞的Toll样受体诱导的白介素-12p70分泌有关。
影响因子：
15.3
作者：
Gautier, G;Humbert, M;Deauvieau, F;Scuiller, M;Hiscott, J;Bates, EEM;Trinchieri, G;Caux, C;Garrone, P
通讯作者：
Garrone, P
影响因子：
20.3
作者：
Weck, Markus Michael;Gruenebach, Frank;Brossart, Peter
通讯作者：
Brossart, Peter
DOI：
10.1073/pnas.092576699
发表时间：
2002-04-30
影响因子：
11.1
作者：
Khayyamian, S;Hutloff, A;Mages, HW
通讯作者：
Mages, HW
影响因子：
15.9
作者：
Prinz, M;Garbe, F;Becher, B
通讯作者：
Becher, B
影响因子：
20.3
作者：
Lundberg, Anna M.;Drexler, Stefan K.;Foxwell, Brian M.
通讯作者：
Foxwell, Brian M.