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CCR6-CCL20 轴作为自身免疫性疾病的治疗靶点。

CCR6-CCL20 axis as a therapeutic target for autoimmune diseases.

机构信息

National Centre for Cell Science, Ganeshkhind, Pune MH-411007, India.

National Centre for Cell Science, Ganeshkhind, Pune MH-411007, India.

出版信息

Autoimmun Rev. 2021 Jul;20(7):102846. doi: 10.1016/j.autrev.2021.102846. Epub 2021 May 7.

Abstract

Chemokine receptor CCR6 is expressed on various cells such as B cells, immature dendritic cells, innate lymphoid cells (ILCs), regulatory CD4 T cells, and Th17 cells. CCL20 is the only known high-affinity ligand that binds to CCR6 and drives CCR6 cells' migration in tissues. CCL20 is mainly produced by epithelial cells, and its expression is increased by several folds under inflammatory conditions. Genome-wide association studies (GWAS) in patients with inflammatory bowel disease (IBD), psoriasis (PS), rheumatoid arthritis (RA), and multiple sclerosis (MS) showed a very strong correlation between the expression of CCR6 and disease severity. It has been shown that disruption of CCR6-CCL20 interaction by using antibodies or antagonists prevents the migration of CCR6 expressing immune cells at the site of inflammation and reduces the severity of the disease. This review discussed the importance of the CCR6-CCL20 axis in IBD, PS, RA, and MS, and recent advances in targeting the CCR6-CCL20 in controlling these autoimmune diseases.

摘要

趋化因子受体 CCR6 在各种细胞上表达,如 B 细胞、未成熟树突状细胞、固有淋巴细胞 (ILC)、调节性 CD4 T 细胞和 Th17 细胞。CCL20 是唯一已知的与 CCR6 结合并驱动 CCR6 细胞在组织中迁移的高亲和力配体。CCL20 主要由上皮细胞产生,在炎症条件下其表达增加几倍。炎症性肠病 (IBD)、银屑病 (PS)、类风湿关节炎 (RA) 和多发性硬化症 (MS) 患者的全基因组关联研究 (GWAS) 显示,CCR6 的表达与疾病严重程度之间存在很强的相关性。已经表明,通过使用抗体或拮抗剂破坏 CCR6-CCL20 相互作用可防止 CCR6 表达的免疫细胞在炎症部位迁移,并减轻疾病的严重程度。本文讨论了 CCR6-CCL20 轴在 IBD、PS、RA 和 MS 中的重要性,以及靶向 CCR6-CCL20 控制这些自身免疫性疾病的最新进展。

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