Cytokine Secretion by CD4+ T Cells at the Immunological Synapse Requires Cdc42-Dependent Local Actin Remodeling but Not Microtubule Organizing Center Polarity
Cytokine Secretion by CD4+ T Cells at the Immunological Synapse Requires Cdc42-Dependent Local Actin Remodeling but Not Microtubule Organizing Center Polarity
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DOI：
10.4049/jimmunol.1200156
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发表时间：
2012-09-01
影响因子：
4.4
通讯作者：
Hivroz, Claire
中科院分区：
文献类型：
--
作者：
Chemin, Karine;Bohineust, Armelle;Hivroz, Claire
T淋巴细胞分泌的细胞因子在建立适应性免疫应答中起着核心作用。然而，人们对新合成的细胞因子一旦产生，如何在T细胞内进行路由以及参与调节其分泌的机制知之甚少。在这项研究中，我们调查的作用，在免疫突触（IS）细胞骨架重塑细胞因子分泌。我们发现，细胞骨架重塑的关键调节因子Rho GTdR Cdc 42控制着原代人CD 4（+）T淋巴细胞分泌IFN-γ。令人惊讶的是，微管组织中心的极性在IS，这并不依赖于Cdc 42，是不需要T淋巴细胞分泌细胞因子，而微管聚合是必需的。相比之下，肌动蛋白重塑在IS，这取决于Cdc 42，控制形成的聚合肌动蛋白环在IS，动态浓度的IFN-γ-含有囊泡在这个环内，和这些囊泡的分泌。这些结果揭示了一个以前未确定的作用Cdc 42依赖肌动蛋白重塑细胞因子胞吐在IS。免疫学杂志，2012，189：2159-2168。
Cytokine secretion by T lymphocytes plays a central role in mounting adaptive immune responses. However, little is known about how newly synthesized cytokines, once produced, are routed within T cells and about the mechanisms involved in regulating their secretions. In this study, we investigated the role of cytoskeleton remodeling at the immunological synapse (IS) in cytokine secretion. We show that a key regulator of cytoskeleton remodeling, the Rho GTPase Cdc42, controls IFN-gamma secretion by primary human CD4(+) T lymphocytes. Surprisingly, microtubule organizing center polarity at the IS, which does not depend on Cdc42, is not required for cytokine secretion by T lymphocytes, whereas microtubule polymerization is required. In contrast, actin remodeling at the IS, which depends on Cdc42, controls the formation of the polymerized actin ring at the IS, the dynamic concentration of IFN-gamma-containing vesicles inside this ring, and the secretion of these vesicles. These results reveal a previously unidentified role of Cdc42-dependent actin remodeling in cytokine exocytosis at the IS. The Journal of Immunology, 2012, 189: 2159-2168.