Mueller Philipp, Massner Jan, Jayachandran Rajesh, Combaluzier Benoit, Albrecht Imke, Gatfield John, Blum Carmen, Ceredig Rod, Rodewald Hans-Reimer, Rolink Antonius G, Pieters Jean
Biozentrum, University of Basel, Klingelbergstrasse 50-70, CH 4056 Basel, Switzerland.
Nat Immunol. 2008 Apr;9(4):424-31. doi: 10.1038/ni1570. Epub 2008 Mar 16.
T cell homeostasis is essential for the functioning of the vertebrate immune system, but the intracellular signals required for T cell homeostasis are largely unknown. We here report that the WD-repeat protein family member coronin-1, encoded by the gene Coro1a, is essential in the mouse for T cell survival through its promotion of Ca2+ mobilization from intracellular stores. Upon T cell receptor triggering, coronin-1 was essential for the generation of inositol-1,4,5-trisphosphate from phosphatidylinositol-4,5-bisphosphate. The absence of coronin-1, although it did not affect T cell development, resulted in a profound defect in Ca2+ mobilization, interleukin-2 production, T cell proliferation and T cell survival. We conclude that coronin-1, through activation of Ca2+ release from intracellular stores, is an essential regulator of peripheral lymphocyte survival.
T细胞稳态对于脊椎动物免疫系统的功能至关重要，但T细胞稳态所需的细胞内信号在很大程度上尚不清楚。我们在此报告，由基因Coro1a编码的WD重复蛋白家族成员冠蛋白-1在小鼠中通过促进细胞内储存库中Ca2+的动员对T细胞存活至关重要。在T细胞受体触发时，冠蛋白-1对于从磷脂酰肌醇-4,5-二磷酸生成肌醇-1,4,5-三磷酸至关重要。冠蛋白-1的缺失虽然不影响T细胞发育，但导致Ca2+动员、白细胞介素-2产生、T细胞增殖和T细胞存活方面的严重缺陷。我们得出结论，冠蛋白-1通过激活细胞内储存库中Ca2+的释放，是外周淋巴细胞存活的重要调节因子。
