Modulation of T Cell Metabolism and Function through Calcium Signaling.
Modulation of T Cell Metabolism and Function through Calcium Signaling.
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DOI：
10.3389/fimmu.2013.00324
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发表时间：
2013-10-11
影响因子：
7.3
通讯作者：
Walsh CM
中科院分区：
文献类型：
--
作者：
Fracchia KM;Pai CY;Walsh CM
作为淋巴细胞活化中的重要第二信使，二价阳离子Ca 2+在适应性免疫应答中起着许多作用。重要的是，Ca2+信号传导对于T细胞活化、自身抗原耐受性和稳态是必不可少的。支持T细胞生物学中Ca2+信号传导的重要作用，Ca2+调节的蛋白磷酸酶钙调神经磷酸酶是预防同种异体移植排斥和自身免疫治疗的药理学抑制的关键靶标。最近的研究强调了Stim1和Orai 1/2蛋白在T细胞背景下调节钙库操纵/钙释放激活的钙（CRAC）通道中的独特作用。虽然已知Ca 2+通过对钙调磷酸酶及其靶点活化T细胞核因子（NFAT）的作用来调节T细胞活化，但这种第二信使也调节其他途径，包括蛋白激酶C、钙调蛋白激酶和细胞骨架蛋白。Ca2+还调节在不同T细胞阶段和亚群中发生的独特代谢变化。在此，我们讨论的手段，其中Ca2+动员调节T细胞受体连接后的细胞代谢。此外，我们强调线粒体代谢，活性氧（ROS）的产生，和CRAC通道活性之间的串扰。作为线粒体ROS和Ca2+调节的靶点，我们描述了丝氨酸/苏氨酸激酶DRAK2在这些过程中的参与。考虑到Ca2+依赖性信号传导和细胞代谢在适应性免疫应答中的重要作用，这些途径之间的串扰可能对T细胞活化、耐受性和稳态的调节很重要。
As a vital second messenger in the activation of lymphocytes, the divalent cation Ca2+ plays numerous roles in adaptive immune responses. Importantly, Ca2+ signaling is essential for T cell activation, tolerance of self-antigens, and homeostasis. Supporting the essential role of Ca2+ signaling in T cell biology, the Ca2+ regulated protein phosphatase calcineurin is a key target of pharmacologic inhibition for preventing allograft rejection and for autoimmune therapy. Recent studies have highlighted the unique role of Stim1 and Orai1/2 proteins in the regulation of store-operated/calcium release activated calcium (CRAC) channels in the context of T cells. While Ca2+ is known to modulate T cell activation via effects on calcineurin and its target, nuclear factor of activated T cells (NFAT), this second messenger also regulates other pathways, including protein kinase C, calmodulin kinases, and cytoskeletal proteins. Ca2+ also modulates the unique metabolic changes that occur during in distinct T cell stages and subsets. Herein, we discuss the means by which Ca2+ mobilization modulates cellular metabolism following T cell receptor ligation. Further, we highlight the crosstalk between mitochondrial metabolism, reactive oxygen species (ROS) generation, and CRAC channel activity. As a target of mitochondrial ROS and Ca2+ regulation, we describe the involvement of the serine/threonine kinase DRAK2 in the context of these processes. Given the important roles for Ca2+ dependent signaling and cellular metabolism in adaptive immune responses, the crosstalk between these pathways is likely to be important for the regulation of T cell activation, tolerance, and homeostasis.
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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
DOI：
10.1073/pnas.47.11.1744
发表时间：
1961-01-01
影响因子：
11.1
作者：
DELUCA, HF;ENGSTROM, GW
通讯作者：
ENGSTROM, GW
影响因子：
4.4
作者：
Arechiga, Adrian F.;Bell, Bryan D.;Walsh, Craig M.
通讯作者：
Walsh, Craig M.
影响因子：
3.8
作者：
Brand, K;Netzker, R;Hamm-Kuenzelmann, B
通讯作者：
Hamm-Kuenzelmann, B
影响因子：
64.5
作者：
Dang EV;Barbi J;Yang HY;Jinasena D;Yu H;Zheng Y;Bordman Z;Fu J;Kim Y;Yen HR;Luo W;Zeller K;Shimoda L;Topalian SL;Semenza GL;Dang CV;Pardoll DM;Pan F
通讯作者：
Pan F