Dynamic Cardiolipin Synthesis Is Required for CD8(+) T Cell Immunity.
Dynamic Cardiolipin Synthesis Is Required for CD8(+) T Cell Immunity.
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DOI：
10.1016/j.cmet.2020.11.003
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发表时间：
2020-12-01
期刊：
影响因子：
29
通讯作者：
Pearce EL
中科院分区：
文献类型：
--
作者：
Corrado M;Edwards-Hicks J;Villa M;Flachsmann LJ;Sanin DE;Jacobs M;Baixauli F;Stanczak M;Anderson E;Azuma M;Quintana A;Curtis JD;Clapes T;Grzes KM;Kabat AM;Kyle R;Patterson AE;Geltink RK;Amulic B;Steward CG;Strathdee D;Trompouki E;O'Sullivan D;Pearce EJ;Pearce EL
线粒体不断适应细胞的代谢需要。这种线粒体可塑性对T细胞至关重要，T细胞根据抗原驱动的信号和环境调节代谢。我们在这里表明，从头合成的线粒体膜特异性脂质心磷脂维持CD8+ T细胞的功能。缺乏心磷脂合成酶PTPMT 1的T细胞心磷脂减少，对抗原的反应很差，因为激活需要基础心磷脂水平。然而，无论是从头心磷脂合成，也不是它的Tafazzin依赖性重塑，T细胞活化所需的。相比之下，PTPMT 1依赖性心磷脂合成是至关重要的线粒体健身时，需要的，最显着的记忆T细胞分化或营养应激。我们还在一小群患有Barth综合征的患者中发现了CD8+ T细胞缺陷，其中TAFAZZIN发生突变，并且在Tafazzin缺陷小鼠模型中发现了CD8 + T细胞缺陷。因此，单个线粒体脂质的动态调节对于CD8+ T细胞免疫至关重要。心磷脂对体内和体外CD8+ T细胞应答至关重要在T细胞分化过程中发生主动心磷脂合成和重塑心磷脂合成支持CD8+ TM细胞发育、代谢和功能在TAZ KO小鼠和Barth综合征患者中T细胞缺陷是明显的Corrado et al.表明线粒体膜特异性脂质心磷脂是有效的CD8+ T细胞功能所必需的代谢可塑性所必需的。心磷脂缺乏的CD8+ T细胞不能对病原体做出反应，也不能适应营养应激。
Mitochondria constantly adapt to the metabolic needs of a cell. This mitochondrial plasticity is critical to T cells, which modulate metabolism depending on antigen-driven signals and environment. We show here that de novo synthesis of the mitochondrial membrane-specific lipid cardiolipin maintains CD8+ T cell function. T cells deficient for the cardiolipin-synthesizing enzyme PTPMT1 had reduced cardiolipin and responded poorly to antigen because basal cardiolipin levels were required for activation. However, neither de novo cardiolipin synthesis, nor its Tafazzin-dependent remodeling, was needed for T cell activation. In contrast, PTPMT1-dependent cardiolipin synthesis was vital when mitochondrial fitness was required, most notably during memory T cell differentiation or nutrient stress. We also found CD8+ T cell defects in a small cohort of patients with Barth syndrome, where TAFAZZIN is mutated, and in a Tafazzin-deficient mouse model. Thus, the dynamic regulation of a single mitochondrial lipid is crucial for CD8+ T cell immunity. Cardiolipin is essential for in vivo and in vitro CD8+ T cell responses Active cardiolipin synthesis and remodeling occurs during T cell differentiation Cardiolipin synthesis supports CD8+ TM cell development, metabolism, and function T cell defects are evident in TAZ KO mice and in Barth syndrome patients Corrado et al. show that the mitochondrial membrane-specific lipid cardiolipin is required for the metabolic plasticity that is essential for effective CD8+ T cell function. Cardiolipin-deficient CD8+ T cells fail to respond to pathogens and are not able to adapt to nutrient stress.
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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
32.4
作者：
Iyer SS;He Q;Janczy JR;Elliott EI;Zhong Z;Olivier AK;Sadler JJ;Knepper-Adrian V;Han R;Qiao L;Eisenbarth SC;Nauseef WM;Cassel SL;Sutterwala FS
通讯作者：
Sutterwala FS
影响因子：
3.7
作者：
Cadalbert LC;Ghaffar FN;Stevenson D;Bryson S;Vaz FM;Gottlieb E;Strathdee D
通讯作者：
Strathdee D
影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
3.7
作者：
Clarke SL;Bowron A;Gonzalez IL;Groves SJ;Newbury-Ecob R;Clayton N;Martin RP;Tsai-Goodman B;Garratt V;Ashworth M;Bowen VM;McCurdy KR;Damin MK;Spencer CT;Toth MJ;Kelley RI;Steward CG
通讯作者：
Steward CG