Tfh cell-derived small extracellular vesicles exacerbate the severity of collagen-induced arthritis by enhancing B-cell responses

Jian Lu; Huimin Zhou; Yuxuan Chen; Xueli Xia; Jun Yang; Jie Ma; Jie Tian; Shengjun Wang

doi:10.1016/j.jaut.2024.103235

Tfh cell-derived small extracellular vesicles exacerbate the severity of collagen-induced arthritis by enhancing B-cell responses

J Autoimmun. 2024 May 1:146:103235. doi: 10.1016/j.jaut.2024.103235. Online ahead of print.

Authors

Jian Lu¹, Huimin Zhou¹, Yuxuan Chen², Xueli Xia², Jun Yang³, Jie Ma², Jie Tian⁴, Shengjun Wang⁵

Affiliations

¹ Department of Laboratory Medicine, Affiliated Hospital, Jiangsu University, Zhenjiang, China; Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.
² Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.
³ Department of Laboratory Medicine, Affiliated People's Hospital, Jiangsu University, Zhenjiang, China.
⁴ Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China. Electronic address: tianjie@ujs.edu.cn.
⁵ Department of Laboratory Medicine, Affiliated Hospital, Jiangsu University, Zhenjiang, China; Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China; Department of Laboratory Medicine, Affiliated People's Hospital, Jiangsu University, Zhenjiang, China. Electronic address: sjwjs@ujs.edu.cn.

PMID: 38696926
DOI: 10.1016/j.jaut.2024.103235

Abstract

Soluble components secreted by Tfh cells are critical for the germinal center responses. In this study, we investigated whether Tfh cells could regulate the B-cell response by releasing small extracellular vesicles (sEVs). Our results showed that Tfh cells promote B-cell differentiation and antibody production through sEVs and that CD40L plays a crucial role in Tfh-sEVs function. In addition, increased Tfh-sEVs were found in mice with collagen-induced arthritis (CIA). Adoptive transfer of Tfh cells significantly exacerbated the severity of CIA; however, the effect of Tfh cells on exacerbating the CIA process was significantly diminished after inhibiting sEVs secretion. Moreover, the levels of plasma Tfh-like-sEVs and CD40L expression on Tfh-like-sEVs in RA patients were significantly higher than those in healthy subjects. In summary, Tfh cell-derived sEVs can enhance the B-cell response, and exacerbate the procession of autoimmune arthritis.

Keywords: B cells; CD40L; Collagen-induced arthritis; Extracellular vesicles; Follicular helper T cells; Rheumatoid arthritis; sEVs.