Endothelial nitric oxide synthase regulates T cell receptor signaling at the immunological synapse
Endothelial nitric oxide synthase regulates T cell receptor signaling at the immunological synapse
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DOI：
10.1016/j.immuni.2006.04.006
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发表时间：
2006-06-01
期刊：
影响因子：
32.4
通讯作者：
Serrador, Juan M.
中科院分区：
文献类型：
--
作者：
Ibiza, Sales;Victor, Victor M.;Serrador, Juan M.
一氧化氮（NO）在T细胞中的作用仍有争议，内源性NO的来源和定位以及是否调节淋巴细胞活化尚不清楚。我们在这里表明，在与抗原结合的几分钟内，T细胞通过内皮型一氧化氮合酶（eNOS）产生NO。这一过程需要增加细胞内Ca2+和磷酸肌肽激酶活性。通过使用eNOS-绿色荧光融合蛋白和荧光探针检测NO，我们发现eNOS与高尔基体一起易位到与抗原呈递细胞（APC）结合的T辅助细胞的免疫突触，在那里eNOS被完全激活。eNOS的过表达阻止了CD3在T细胞- apc接触位点的中心结合，这伴随着CD3链、ZAP-70和细胞外信号调节激酶的磷酸化增加，ifn - γ合成增加，但IL-2的产生减少。因此，enos衍生的NO选择性地增强了免疫突触上T细胞受体对抗原的信号传导。
The role of nitric oxide (NO) in T cells remains controversial, and the origin and localization of endogenous NO and whether it regulates lymphocyte activation are unclear. We show here that, within minutes of binding to antigen, T cells produce NO via endothelial nitric oxide synthase (eNOS). This process required increased intracellular Ca2+ and phosphoinositide3-kinase activity. Ely using an eNOS-green fluorescent fusion protein and fluorescent probes to detect NO, we show that eNOS translocates with the Golgi apparatus to the immune synapse of T helper cells engaged with antigen-presenting cells (APC), where it was fully activated. Overexpression of eNOS prevented the central coalescence of CD3 at the T cell-APC contact site, which was accompanied by increased phosphorylation of CD3 chain, ZAP-70, and extracellular signal-regulated kinases and increased IFN-gamma synthesis, but reduced production of IL-2. Therefore, eNOS-derived NO selectively potentiates T cell receptor signaling to antigen at the immunological synapse.