类风湿关节炎的一种创新免疫治疗策略：通过靶向胸腺细胞抗原-1的全人源抗体选择性抑制血管生成和破骨细胞分化。

An innovative immunotherapeutic strategy for rheumatoid arthritis: Selectively suppressing angiogenesis and osteoclast differentiation by fully human antibody targeting thymocyte antigen-1.

作者信息

Hu Xuanxuan, Li Meiqi, Zhang Yu, Sang Kanru, Zhang Yejun, Li Wulan, Liu Bo, Wan Leyu, Du Bang, Qian Jinheng, Meng Fanxi, Fu Yanneng, Dai Meijuan, Gao Guohui, Ye Hui

机构信息

School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

The First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

出版信息

Exp Cell Res. 2023 Mar 1;424(1):113490. doi: 10.1016/j.yexcr.2023.113490. Epub 2023 Jan 24.

DOI:10.1016/j.yexcr.2023.113490

PMID:36706943

Abstract

Thymocyte antigen-1 (THY-1)is a potential target for rheumatoid arthritis (RA) treatment, and THY-1 positive fibroblast-like synoviocytes (FLS) are enriched in the synovium of RA patients and participate in angiogenesis to accelerate RA progression. In this study, we screened an antibody targeting THY-1 (THY-1 Ab) and explored its mechanism in alleviating RA progression. THY-1 Ab was screened from ScFv phage antibody library by phage display technology (PDT). THY-1 Ab-treated collagen induced arthritis (CIA) mice had lower degree of arthritis scores. We explore the mechanism of THY-1 Ab in alleviating RA progression. THY-1 Ab can remarkably inhibit the secretion of pro-inflammatory factors and promote the secretion of anti-inflammatory factors. Further experiments showed that THY1 Ab downregulated the expression of JUNB by the hsa_circ_0094342/miRNA-155-5P/SPI1 axis, inhibited RA angiogenesis and osteoclast differentiation, and relieved RA progression. These findings support that THY-1 Ab is a promising therapeutic antibody for RA treatment.

摘要

胸腺细胞抗原-1（THY-1）是类风湿关节炎（RA）治疗的潜在靶点，THY-1阳性成纤维样滑膜细胞（FLS）在RA患者滑膜中富集，并参与血管生成以加速RA进展。在本研究中，我们筛选了一种靶向THY-1的抗体（THY-1 Ab）并探讨其缓解RA进展的机制。通过噬菌体展示技术（PDT）从单链抗体噬菌体抗体库中筛选出THY-1 Ab。用THY-1 Ab处理的胶原诱导性关节炎（CIA）小鼠的关节炎评分较低。我们探讨了THY-1 Ab缓解RA进展的机制。THY-1 Ab可显著抑制促炎因子的分泌并促进抗炎因子的分泌。进一步实验表明，THY1 Ab通过hsa_circ_0094342/miRNA-155-5P/SPI1轴下调JUNB的表达，抑制RA血管生成和破骨细胞分化，并缓解RA进展。这些发现支持THY-1 Ab是一种有前景的RA治疗性抗体。