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瓜氨酸化抗原疫苗治疗自身免疫性关节炎。

A citrullinated antigenic vaccine in treatment of autoimmune arthritis.

机构信息

Department of Rheumatology and Immunology, Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis, Beijing 100044, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Sci Bull (Beijing). 2024 Sep 30;69(18):2920-2929. doi: 10.1016/j.scib.2024.02.042. Epub 2024 Aug 6.

Abstract

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease triggered by antigenic peptides with environmental and genetic risk factors. It has been shown that antigen-specific targeting could be a promising therapeutical strategy for RA by restoring immune tolerance to self-antigens without compromising normal immunity. Citrullination of antigens enhances antigenic properties and induces autoimmune responses. Here, we showed that citrullinated antigenic (citAg) vaccine ameliorated collagen-induced arthritis with decreased T-helper 1 (Th1) and Th17 cells, downregulated proinflammatory cytokines including interlukin-6 and tumor necrosis factor-α, and inhibited antigen recall responses. B cell receptor sequencing further revealed that citAg vaccine could dampen the dysregulated V(D)J recombination, restoring the immune repertoire. Taken together, the results demonstrated that citAg vaccine might have a therapeutic effect on RA.

摘要

类风湿关节炎(RA)是一种炎症性自身免疫性疾病,由抗原肽触发,具有环境和遗传风险因素。已经表明,通过恢复对自身抗原的免疫耐受而不损害正常免疫,抗原特异性靶向可能是 RA 的一种有前途的治疗策略。抗原的瓜氨酸化增强了抗原性,并诱导自身免疫反应。在这里,我们表明瓜氨酸化抗原(citAg)疫苗通过减少辅助性 T 细胞 1(Th1)和 Th17 细胞,下调包括白细胞介素 6 和肿瘤坏死因子-α在内的促炎细胞因子,并抑制抗原回忆反应,改善了胶原诱导性关节炎。B 细胞受体测序进一步表明,citAg 疫苗可以抑制失调的 V(D)J 重组,恢复免疫库。总之,这些结果表明 citAg 疫苗可能对 RA 具有治疗作用。

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