趋化因子受体 CCR7 是类风湿关节炎治疗的一个有前途的靶点。
The chemokine receptor CCR7 is a promising target for rheumatoid arthritis therapy.
机构信息
Institute of Immunology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
Pepscan Therapeutics BV, Lelystad, The Netherlands.
出版信息
Cell Mol Immunol. 2019 Oct;16(10):791-799. doi: 10.1038/s41423-018-0056-5. Epub 2018 Jul 4.
Abstract
The chemokine receptor CCR7 and its ligands CCL19 and CCL21 guide the homing and positioning of dendritic and T cells in lymphoid organs, thereby contributing to several aspects of adaptive immunity and immune tolerance. In the present study, we investigated the role of CCR7 in the pathogenesis of collagen-induced arthritis (CIA). By using a novel anti-human CCR7 antibody and humanized CCR7 mice, we evaluated CCR7 as a target in this autoimmune model of rheumatoid arthritis (RA). Ccr7-deficient mice were completely resistant to CIA and presented severely impaired antibody responses to collagen II (CII). Selective CCR7 expression on dendritic cells restored arthritis severity and anti-CII antibody titers. Prophylactic and therapeutic treatment of humanized CCR7 mice with anti-human CCR7 mAb 8H3-16A12 led to complete resistance to CIA and halted CIA progression, respectively. Our data demonstrate that CCR7 signaling is essential for the induction of CIA and identify CCR7 as a potential therapeutic target in RA.
摘要
趋化因子受体 CCR7 及其配体 CCL19 和 CCL21 指导树突状细胞和 T 细胞在淋巴器官中的归巢和定位，从而有助于适应性免疫和免疫耐受的几个方面。在本研究中，我们研究了 CCR7 在胶原诱导性关节炎 (CIA) 发病机制中的作用。通过使用新型抗人 CCR7 抗体和人源化 CCR7 小鼠，我们评估了 CCR7 作为类风湿关节炎 (RA) 这一自身免疫模型中的靶点。缺乏 Ccr7 的小鼠对 CIA 完全具有抗性，并且对胶原蛋白 II (CII) 的抗体反应严重受损。树突状细胞上的选择性 CCR7 表达恢复了关节炎的严重程度和抗 CII 抗体滴度。用抗人 CCR7 mAb 8H3-16A12 对人源化 CCR7 小鼠进行预防性和治疗性治疗分别导致完全抵抗 CIA 和阻止 CIA 进展。我们的数据表明 CCR7 信号对于 CIA 的诱导是必需的，并将 CCR7 确定为 RA 中的潜在治疗靶点。
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