Autophagy-Mediated Activation of Mucosal-Associated Invariant T Cells Driven by Mesenchymal Stem Cell-Derived IL-15.
Autophagy-Mediated Activation of Mucosal-Associated Invariant T Cells Driven by Mesenchymal Stem Cell-Derived IL-15.
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由间充质干细胞衍生的 IL-15 驱动的自噬介导的粘膜相关恒定 T 细胞的激活
DOI：
10.1016/j.stemcr.2021.03.005
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发表时间：
2021-04-13
影响因子：
5.9
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Ye G;Wang P;Xie Z;Cao Q;Li J;Zheng G;Wang S;Li M;Liu W;Cen S;Li Z;Yu W;Wu Y;Shen H
粘膜相关不变T细胞(MAIT)是一种先天的非常规T细胞，在人类中大量存在，近年来引起了越来越多的关注。间充质干细胞(MSCs)是免疫细胞的重要调节因子。然而，MAIT细胞是否受MSCs调控尚不清楚。在此，我们探索了MSCs对MAIT细胞的作用，并揭示了其潜在的机制。结果发现，骨髓间充质干细胞不影响MAIT细胞的增殖，但可显著诱导MAIT细胞表面CD69、肿瘤坏死因子-α、干扰素-γ和颗粒酶B的表达增加，并且MSCs通过分泌IL-15以非TCRMR1的方式激活MAIT细胞。我们发现，MSC来源的IL-15通过增强自噬活性来激活MAIT细胞，自噬活性被自噬抑制剂3-甲基腺嘌呤所消除。根据我们的发现，骨髓间充质干细胞通过IL-15诱导的自噬激活MAIT细胞，这可能有助于阐明某些免疫反应和疾病的机制，并为未来的研究提供指导。骨髓间充质干细胞通过分泌IL-15激活MAIT细胞表达高水平的肿瘤坏死因子-α、干扰素-γ和颗粒酶B。在本文中，MSC来源的IL-15通过增强自噬活性来激活MAIT细胞。沈慧勇及其同事证明，MSCs不影响MAIT细胞的增殖，但显著诱导MAIT细胞的活化表型，其表达增加CD69、肿瘤坏死因子-α、干扰素-γ和颗粒酶B。
Mucosal-associated invariant T (MAIT) cells are innate-like unconventional T cells that are abundant in humans and have attracted increasing attention in recent years. Mesenchymal stem cells (MSCs) are crucial regulators of immune cells. However, whether MAIT cells are regulated by MSCs is unclear. Here, we explored the effect of MSCs on MAIT cells and revealed the underlying mechanism. We found that MSCs did not influence the proliferation of MAIT cells but strikingly induced an activated phenotype with an increased expression of CD69, TNF-α, IFN-γ, and granzyme B. Moreover, MSCs activated MAIT cells in a TCR-MR1-independent mechanism through MSC-secreted IL-15. We revealed that MSC-derived IL-15 activated MAIT cells by enhancing autophagy activity, which was abolished by the autophagy inhibitor 3-methyladenine. Based on our findings, MAIT cells are activated by MSCs through IL-15-induced autophagy, which may help elucidate the mechanisms underlying some immune responses and diseases and provide guidance for future research. MSCs activate MAIT cells to express higher levels of TNF-α, IFN-γ, and granzyme B MAIT cells are activated in a TCR-MR1-independent way through MSC-secreted IL-15 MSC-derived IL-15 activates MAIT cells by enhancing autophagy activity In this article, Shen Huiyong and colleagues show that MSCs do not influence the proliferation of MAIT cells but strikingly induce an activated phenotype with an increased expression of CD69, TNF-α, IFN-γ, and granzyme B. Mechanistically, MSC-derived IL-15 enhances the autophagy level of MAIT cells and results in MAIT cell activation.
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影响因子：
5.6
作者：
Fan L;Hu C;Chen J;Cen P;Wang J;Li L
通讯作者：
Li L
影响因子：
7.3
作者：
Chiba A;Murayama G;Miyake S
通讯作者：
Miyake S
影响因子：
7.5
作者：
Cen, Shuizhong;Wang, Peng;Wu, Yanfeng
通讯作者：
Wu, Yanfeng
DOI：
10.1007/978-1-4939-2938-2_4
发表时间：
2015-01-01
期刊：
CARTILAGE TISSUE ENGINEERING: METHODS AND PROTOCOLS
影响因子：
--
作者：
Mahmoudifar, Nastaran;Doran, Pauline M.
通讯作者：
Doran, Pauline M.
影响因子：
20.3
作者：
Leeansyah, Edwin;Ganesh, Anupama;Sandberg, Johan K.
通讯作者：
Sandberg, Johan K.