细胞外囊泡相关的GARP/TGFβ:LAP介质"传染性"耐受性
William J Burlingham1, Ewa Jankowska-Gan1, John H Fechner1
1Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI.
Transplantation direct
|May 30, 2023
概括
调控性T细胞释放带有潜伏转化生长因子β (TGFβ) 的外体:延迟相关 (LAP) /糖蛋白A重复占主导地位 (GARP) 复合体. 这些外体复合体通过直接作用或通过旁观者T细胞吸收后抑制免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 细胞外囊泡 细胞外囊泡
背景情况:
- 调节性T细胞 (Tregs) 对于维持免疫耐受性至关重要.
- 小型细胞外囊泡 (sEVs),包括外体,是细胞间通信的关键媒介.
- 潜伏转化生长因子β (TGFβ):已知潜伏相关 (LAP) /糖蛋白A重复占主导地位 (GARP) 复合体具有免疫抑制作用.
研究的目的:
- 为了调查TGFβ:LAP/GARP复合体是否与淋巴细胞衍生的sEVs有关.
- 为了确定这些与sEV相关的复合物是否可以抑制免疫反应.
- 探索由这些SEV介导的TGFβ激活和抑制的机制.
主要方法:
- 在C57BL/6小鼠中诱导耐受性.
- 隔离和重新刺激淋巴细胞以诱导sEV的产生.
- 超离心以隔离sEVs从培养上游生物中.
- 与酶相关的免疫吸收试验 (ELISA) 检测TGFβ:LAP,GARP和四素 (CD81,CD63,CD9).
- 使用延迟型过敏性试验评估TGFβ依赖的免疫抑制功能.
主要成果:
- 来自耐受性小鼠的淋巴细胞分泌了GARP/TGFβ:LAP涂层的细胞外囊泡.
- GARP/TGFβ:LAP主要与CD81+外体有关,类似于IL35.
- 与sEV结合的GARP/TGFβ:LAP在初级和二级反应中都表现出免疫抑制活性.
- 二次抑制需要旁观者T细胞吸收sEV并在其表面重新表达.
结论:
- 由特异性Tregs产生的外体GARP/TGFβ:LAP可以调解免疫抑制.
- 激活发生在立即 (初级抑制) 或在内化和被天真T细胞重新表达后 (二级抑制).
- 这意味着外体TGFβ:LAP和Treg衍生的GARP在传染性耐受性网络中.
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