Newly synthesized AIFM1 determines the hypersensitivity of T lymphocytes to STING activation-induced cell apoptosis.
Newly synthesized AIFM1 determines the hypersensitivity of T lymphocytes to STING activation-induced cell apoptosis.
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新合成的 AIFM1 决定 T 淋巴细胞对 STING 激活诱导的细胞凋亡的超敏性。
DOI：
10.1016/j.celrep.2023.112327
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发表时间：
2023
期刊：
影响因子：
8.8
通讯作者：
Xinqi Liu
中科院分区：
文献类型：
--
作者：
Wangsheng Ji;Lianfei Zhang;Chengxin Ma;Xiaoyu Xu;Shuai Li;Huan Xia;Wei;Xinqi Liu
STING是一种众所周知的信号转导衔接子，对于感测胞质dsDNA以产生I型干扰素至关重要。虽然详细的潜在机制仍然是谜，最近的研究表明，STING激活可以导致T淋巴细胞凋亡。在这里，我们报告说，AIFM 1促进STING激活诱导的T淋巴细胞细胞凋亡。从机制上讲，AIFM 1在T细胞中的STING活化后上调，但在HEK 293 T-STING和THP-1细胞中不上调，使T细胞对细胞凋亡更敏感。与AIFM 1在caspase非依赖性死亡中的典型作用相反，AIFM 1的功能是通过形成AIFM 1/IRF 3/BAX复合物和线粒体外膜透化来操作的，这导致细胞色素释放和caspase激活。此外，补充新合成的AIFM 1可以重建HEK 293 T-STING和THP-1细胞中STING激活诱导的细胞凋亡。我们的研究确定AIFM 1是决定T淋巴细胞对STING激活诱导的细胞凋亡的超敏性的关键调节因子。
STING is a well-known signaling adaptor essential for sensing cytosolic dsDNA to produce type I interferon. Although the detailed underlying mechanisms remain enigmatic, recent studies show that STING activation can lead to T lymphocyte apoptosis. Here, we report that AIFM1 facilitates STING activation-induced cell apoptosis in T lymphocytes. Mechanistically, AIFM1 is upregulated after STING activation in T cells but not in HEK293T-STING and THP-1 cells, rendering T cells more sensitive to apoptosis. In contrast to the canonical role of AIFM1 in the caspase-independent parthanatos, the function of AIFM1 is operated by the formation of an AIFM1/IRF3/BAX complex and mitochondrial outer membrane permeabilization, which cause cytochromecrelease and caspase activation. Furthermore, supplementation with newly synthesized AIFM1 can reconstitute STING activation-induced cell apoptosis in HEK293T-STING and THP-1 cells. Our study identifies AIFM1 as a key regulating factor determining the hypersensitivity of T lymphocytes to STING activation-induced cell apoptosis.
DOI：
10.1056/nejmoa1312625
发表时间：
2014-08-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Liu Y;Jesus AA;Marrero B;Yang D;Ramsey SE;Sanchez GAM;Tenbrock K;Wittkowski H;Jones OY;Kuehn HS;Lee CR;DiMattia MA;Cowen EW;Gonzalez B;Palmer I;DiGiovanna JJ;Biancotto A;Kim H;Tsai WL;Trier AM;Huang Y;Stone DL;Hill S;Kim HJ;St Hilaire C;Gurprasad S;Plass N;Chapelle D;Horkayne-Szakaly I;Foell D;Barysenka A;Candotti F;Holland SM;Hughes JD;Mehmet H;Issekutz AC;Raffeld M;McElwee J;Fontana JR;Minniti CP;Moir S;Kastner DL;Gadina M;Steven AC;Wingfield PT;Brooks SR;Rosenzweig SD;Fleisher TA;Deng Z;Boehm M;Paller AS;Goldbach-Mansky R
通讯作者：
Goldbach-Mansky R
影响因子：
32.4
作者：
Wu, Jianjun;Dobbs, Nicole;Yan, Nan
通讯作者：
Yan, Nan