https://scholars.lib.ntu.edu.tw/handle/123456789/641483
標題: | TRAF3-EWSR1 signaling axis acts as a checkpoint on germinal center responses | 作者: | Li, Yanchuan Zhu, Lele Chun-Jung Ko Yang, Jin-Young Wang, Hongjiao Manyam, Ganiraju Wang, Jing Cheng, Xuhong Zhao, Shuli Jie, Zuliang |
公開日期: | 7-八月-2023 | 出版社: | ROCKEFELLER UNIV PRESS | 卷: | 220 | 期: | 8 | 來源出版物: | The Journal of experimental medicine | 摘要: | The formation of germinal centers (GCs) is crucial for humoral immunity and vaccine efficacy. Constant stimulation through microbiota drives the formation of constitutive GCs in Peyer's patches (PPs), which generate B cells that produce antibodies against gut antigens derived from commensal bacteria and infectious pathogens. However, the molecular mechanism that regulates this persistent process is poorly understood. We report that Ewing Sarcoma Breakpoint Region 1 (EWSR1) is a brake to constitutive GC generation and immunoglobulin G (IgG) production in PPs, vaccination-induced GC formation, and IgG responses. Mechanistically, EWSR1 suppresses Bcl6 upregulation after antigen encounter, thereby negatively regulating induced GC B cell generation and IgG production. We further showed that tumor necrosis factor receptor-associated factor (TRAF) 3 serves as a negative regulator of EWSR1. These results established that the TRAF3-EWSR1 signaling axis acts as a checkpoint for Bcl6 expression and GC responses, indicating that this axis is a therapeutic target to tune GC responses and humoral immunity in infectious diseases. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/641483 | ISSN: | 0022-1007 1540-9538 |
DOI: | 10.1084/jem.20221483 |
顯示於: | 免疫學研究所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。