Cornely Rhea, Pollock Abigail H, Rentero Carles, Norris Sarah E, Alvarez-Guaita Anna, Grewal Thomas, Mitchell Todd, Enrich Carlos, Moss Stephen E, Parton Robert G, Rossy Jérémie, Gaus Katharina
EMBL Australia Node in Single Molecule Science, School of Medical Science, University of New South Wales (UNSW), Sydney, New South Wales, Australia.
Departament de Biologia Cellular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
Immunol Cell Biol. 2016 Jul;94(6):543-53. doi: 10.1038/icb.2016.15. Epub 2016 Feb 8.
Annexin A6 (AnxA6) has been implicated in cell signalling by contributing to the organisation of the plasma membrane. Here we examined whether AnxA6 regulates signalling and proliferation in T cells. We used a contact hypersensitivity model to immune challenge wild-type (WT) and AnxA6(-/-) mice and found that the in vivo proliferation of CD4(+) T cells, but not CD8(+) T cells, was impaired in AnxA6(-/-) relative to WT mice. However, T-cell migration and signalling through the T-cell receptor ex vivo was similar between T cells isolated from AnxA6(-/-) and WT mice. In contrast, interleukin-2 (IL-2) signalling was reduced in AnxA6(-/-) compared with WT T cells. Further, AnxA6-deficient T cells had reduced membrane order and cholesterol levels. Taken together, our data suggest that AnxA6 regulates IL-2 homeostasis and sensitivity in T cells by sustaining a lipid raft-like membrane environment.
膜联蛋白A6（AnxA6）通过参与质膜的组织而与细胞信号传导有关。在此，我们研究了AnxA6是否调节T细胞中的信号传导和增殖。我们使用接触性超敏反应模型对野生型（WT）和AnxA6基因敲除（AnxA6(-/-)）小鼠进行免疫攻击，发现相对于WT小鼠，AnxA6(-/-)小鼠体内CD4(+) T细胞的增殖受损，但CD8(+) T细胞不受影响。然而，从AnxA6(-/-)和WT小鼠分离的T细胞在体外通过T细胞受体的迁移和信号传导相似。相比之下，与WT T细胞相比，AnxA6(-/-)中的白细胞介素-2（IL-2）信号传导减少。此外，AnxA6缺陷型T细胞的膜有序性和胆固醇水平降低。综上所述，我们的数据表明，AnxA6通过维持类脂筏膜环境来调节T细胞中的IL-2稳态和敏感性。
