ETV5 promotes lupus pathogenesis and follicular helper T cell differentiation by inducing osteopontin expression

• 成果类型: Article
• 署名作者: Park, Jiho; Lee, Jongeun; Hur, Yunjung; Kim, Chan- Johng; Kim, Han Bit; Um, Dahun; Kim, Da Som; Lee, June - Yong; Park, Sungjun; Park, Youngjae; Kim, Tae- Kyung; Im, Sin- Hyeog; Kim, Sung Won; Kwok, Seung- Ki; Lee, Yoontae
• 署名单位: Pohang University of Science & Technology (POSTECH); Catholic University of Korea; Yonsei University; Yonsei University Health System; Yonsei University; Yonsei University Health System; Korea Research Institute of Chemical Technology (KRICT); Catholic University of Korea; Seoul St. Mary's Hospital; Yonsei University; Catholic University of Korea; Seoul St. Mary's Hospital
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11154
• DOI: 10.1073/pnas.2322009121
• 发表日期: 2024-06-11
• 关键词: glucose-metabolism; disease-activity; induction; subset; bcl6; erythematosus; autoimmunity; modulation; activation; expansion

摘要

Follicular helper T (T FH ) cells mediate germinal center reactions to generate high affinity antibodies against specific pathogens, and their excessive production is associated with the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). ETV5, a member of the ETS transcription factor family, promotes T FH cell differentiation in mice. In this study, we examined the role of ETV5 in the pathogenesis of lupus in mice and humans. T cell-specific deletion of Etv5 alleles ameliorated T FH cell differentiation and autoimmune phenotypes in lupus mouse models. Further, we identified SPP1 as an ETV5 target that promotes T FH cell differentiation in both mice and humans. Notably, extracellular osteopontin (OPN) encoded by SPP1 enhances T FH cell differentiation by activating the CD44 - AKT signaling pathway. Furthermore, ETV5 and SPP1 levels were increased in CD4 + T cells from patients with SLE and were positively correlated with disease activity. Taken together, our findings demonstrate that ETV5 is a lupus - promoting transcription factor, and secreted OPN promotes T FH cell differentiation.