Hedgehog signaling controls T cell killing at the immunological synapse.

Hedgehog signaling controls T cell killing at the immunological synapse.
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DOI:
10.1126/science.1244689
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发表时间:
2013-12-06
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Griffiths GM
Griffiths GM
中科院分区:
其他
文献类型:
--
作者:
de la Roche M;Ritter AT;Angus KL;Dinsmore C;Earnshaw CH;Reiter JF;Griffiths GM

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中心体对细胞毒性T淋巴细胞(CTL)的功能至关重要,它与质膜接触并指导细胞毒性颗粒在免疫突触分泌。中心体在质膜的对接也发生在纤毛形成过程中。在非造血细胞中形成的初级纤毛对脊椎动物的Hedgehog (Hh)信号传导至关重要。淋巴细胞不形成初级纤毛,但我们发现并描述了Hh信号在CTL杀伤中起重要作用。T细胞受体激活,用细胞毒性颗粒“预先武装”ctl,也启动了Hh信号传导。Hh通路在细胞内激活并触发Rac1合成。这些事件通过促进中心体极化和颗粒释放所需的肌动蛋白重塑来“预先武装”ctl。因此,Hh信号在CTL功能中起作用,免疫突触可能代表了一种修饰的纤毛。
The centrosome is essential for cytotoxic T lymphocyte (CTL) function, contacting the plasma membrane and directing cytotoxic granules for secretion at the immunological synapse. Centrosome docking at the plasma membrane also occurs during cilia formation. The primary cilium, formed in nonhematopoietic cells, is essential for vertebrate Hedgehog (Hh) signaling. Lymphocytes do not form primary cilia, but we found and describe here that Hh signaling played an important role in CTL killing. T cell receptor activation, which “prearms” CTLs with cytotoxic granules, also initiated Hh signaling. Hh pathway activation occurred intracellularly and triggered Rac1 synthesis. These events “prearmed” CTLs for action by promoting the actin remodeling required for centrosome polarization and granule release. Thus, Hh signaling plays a role in CTL function, and the immunological synapse may represent a modified cilium.
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