淋巴毒素
淋巴毒素β受体
医学
淋巴系统
免疫学
受体
细胞生物学
信号转导
癌症研究
淋巴毒素α
内科学
生物
作者
Huazhen Liu,Helong Dai,Feifei Qiu,Yuchao Chen,Chun-Ling Liang,Bin Yang,Nianqiao Gong,Jonathan S. Bromberg,Zhenhua Dai
标识
DOI:10.1016/j.ajt.2024.06.019
摘要
Conventional immunosuppressants that suppress allograft rejection cause various side effects. Although regulatory T cells (Tregs) are essential for allograft survival, the limited efficacy of Treg therapy demands improvement. Thus, it is imperative to seek new approaches to enhancing Treg suppression. Low-intensity electrostimulation (ES) has been shown to exert antiinflammatory effects without causing major adverse reactions. However, it remains unknown whether and how ES regulates alloimmunity. Here, we found that regional ES delayed murine skin allograft rejection and promoted long-term allograft survival induced by an mTOR inhibitor, rapamycin. ES also extended islet allograft survival. Mechanistically, ES enhanced the expression of lymphotoxin α (LTα) on Tregs after transplantation. Blockade of lymphotoxin β receptor-mediated nonclassical NFκB signaling suppressed lymphatic Treg migration and largely reversed the effects of ES on allograft survival. Moreover, ES failed to extend allograft survival when recipients lacked LTα/lymph nodes or if transferred Tregs lacked LTα. Therefore, ES promoted the lymphatic migration of CD4
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