Hydroxychloroquine Alleviates EAU by Inhibiting Uveitogenic T Cells and Ameliorating Retinal Vascular Endothelial Cells Dysfunction.
Hydroxychloroquine Alleviates EAU by Inhibiting Uveitogenic T Cells and Ameliorating Retinal Vascular Endothelial Cells Dysfunction.
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羟氯喹通过抑制葡萄膜炎性 T 细胞和改善视网膜血管内皮细胞功能障碍来缓解 EAU
DOI：
10.3389/fimmu.2022.859260
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发表时间：
2022
影响因子：
7.3
通讯作者：
Liang D
中科院分区：
文献类型：
--
作者：
Hu Y;Li Z;Chen G;Li Z;Huang J;Huang H;Xie Y;Chen Q;Zhu W;Wang M;Chen J;Su W;Chen X;Liang D
炎症触发CD 4 +T细胞的活化和血-视网膜屏障的破坏，从而促成实验性自身免疫性葡萄膜炎（EAU）的病理。我们探讨了羟氯喹（HCQ）对EAU的抗炎作用及其在T细胞和视网膜血管内皮细胞（RVECs）中的作用机制。C57 BL/6 J小鼠用光感受器间类维生素A结合蛋白1-20（IRBP 1 -20）免疫以诱导EAU，然后用媒介物或HCQ（100 mg/kg/天）处理。在免疫后第7、14、21、30和60天，评价临床评分。在第14天，评估组织病理学评分，并收集视网膜、脾脏和淋巴结用于定量聚合酶链反应或流式细胞术分析。用肿瘤坏死因子α（TNF-α）刺激RVEC，诱导RVEC功能障碍。检测细胞因子、趋化因子、粘附分子和凝集素样氧化低密度脂蛋白受体1（LOX-1）/核因子κB（NF-κB）在有或无HCQ的RVEC中的表达。HCQ治疗保护小鼠免受葡萄膜炎，这通过视网膜中炎性因子、趋化因子和粘附分子的表达减少来证明。在系统免疫应答中，HCQ抑制初始CD 4 +T细胞的活化和T效应细胞的频率，并促进调节性T细胞。HCQ在体外降低IRBP 1 -20特异性T细胞应答和CD 4 +T细胞增殖。进一步的研究证实TNF-α诱导RVEC表达炎性细胞因子、趋化因子和粘附分子，而HCQ通过LOX-1/NF-κB途径减轻这种改变。HCQ通过LOX-1/NF-κB轴调节Teff/Treg平衡和改善RVECs功能障碍来减轻EAU。HCQ可能是一种有前途的治疗葡萄膜炎的候选药物。
Inflammation triggers the activation of CD4+T cells and the breakdown of blood–retinal barrier, thus contributing to the pathology of experimental autoimmune uveitis (EAU). We explored the anti-inflammatory effect of hydroxychloroquine (HCQ) on EAU and the potential mechanisms active in T cells and retinal vascular endothelial cells (RVECs). C57BL/6J mice were immunized with interphotoreceptor retinoid binding protein 1-20 (IRBP1–20) to induce EAU and then treated with the vehicle or HCQ (100 mg/kg/day). On day 7, 14, 21, 30 and 60 after immunization, clinical scores were evaluated. On day 14, histopathological scores were assessed, and retinas, spleens, and lymph nodes were collected for quantitative polymerase chain reaction or flow cytometry analysis. RVEC dysfunction was induced by tumor necrosis factor α (TNF-α) stimulation. The expression of cytokines, chemokines, adhesion molecules, and lectin-like oxidized LDL receptor-1 (LOX-1)/nuclear factor κB (NF-κB) was measured in RVECs with or without HCQ. HCQ treatment protected mice from uveitis, evidenced by reduced expression of inflammatory factors, chemokines, and adhesion molecules in the retina. In systemic immune response, HCQ inhibited the activation of naïve CD4+T cells and frequencies of T effector cells, and promoted T regulatory cells. HCQ decreased IRBP1-20–specific T cell responses and proliferation of CD4+T cells in vitro. Further studies established that TNF-α induced RVECs to express inflammatory cytokines, chemokines, and adhesion molecules, whereas HCQ alleviated the alterations via the LOX-1/NF-κB pathways. HCQ alleviates EAU by regulating the Teff/Treg balance and ameliorating RVECs dysfunction via the LOX-1/NF-κB axis. HCQ may be a promising therapeutic candidate for uveitis.
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影响因子：
9.3
作者：
Lipski DA;Dewispelaere R;Foucart V;Caspers LE;Defrance M;Bruyns C;Willermain F
通讯作者：
Willermain F
影响因子：
10.8
作者：
Akhmedov, Alexander;Crucet, Margot;Luescher, Thomas F.
通讯作者：
Luescher, Thomas F.
氯喹和羟氯喹在针对眼眶成纤维细胞的格雷夫斯眼眶病治疗中的新作用
影响因子：
5.8
作者：
Guo, Yan;Li, Hai;Li, Yanbing
通讯作者：
Li, Yanbing
DOI：
10.1016/j.preghy.2016.09.001
发表时间：
2016-10-01
影响因子：
2.2
作者：
Rahman, Rahana;Murthi, Padma;Wallace, Euan M.
通讯作者：
Wallace, Euan M.
影响因子：
4.4
作者：
Koch, Marcus W.;Zabad, Rana;Yong, V. Wee
通讯作者：
Yong, V. Wee