RORγt+ cells selectively express redundant cation channels linked to the Golgi apparatus.
RORγt+ cells selectively express redundant cation channels linked to the Golgi apparatus.
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DOI：
10.1038/srep23682
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发表时间：
2016-03-24
影响因子：
4.6
通讯作者：
Louvet C
中科院分区：
文献类型：
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作者：
Drujont L;Lemoine A;Moreau A;Bienvenu G;Lancien M;Cens T;Guillot F;Bériou G;Bouchet-Delbos L;Fehling HJ;Chiffoleau E;Nicot AB;Charnet P;Martin JC;Josien R;Cuturi MC;Louvet C
类维生素A相关孤儿受体γ t（RORγt）是17型免疫的主要转录因子，涉及T辅助细胞17、第3组先天淋巴细胞或产生IL-17的γδ T细胞。在这里，我们发现细胞内离子通道TMEM 176 B及其同源物TMEM 176 A在这些RORγt+细胞中强烈表达。我们证明，TMEM 176 A和B表现出类似的阳离子通道活性，主要是共定位在靠近trans-Golgi网络。引人注目的是，在小鼠中，Tmem 176 b的丢失与Tmem 176 a的强烈上调系统性相关。虽然Tmem 176 b单一缺陷对实验性自身免疫性脑脊髓炎、T细胞或DSS诱导的结肠炎的过程没有影响，但它显著减少了咪喹莫特诱导的银屑病样皮肤炎症。这些发现揭示了一个潜在的新的特定过程，与后高尔基体运输调节RORγt+细胞的功能，并表明，这两个同源物应同时靶向明确阐明这种细胞内离子流的作用。
Retinoid-related orphan receptor gamma t (RORγt) is a master transcription factor central to type 17 immunity involving cells such as T helper 17, group 3 innate lymphoid cells or IL-17-producing γδ T cells. Here we show that the intracellular ion channel TMEM176B and its homologue TMEM176A are strongly expressed in these RORγt+ cells. We demonstrate that TMEM176A and B exhibit a similar cation channel activity and mainly colocalise in close proximity to the trans-Golgi network. Strikingly, in the mouse, the loss of Tmem176b is systematically associated with a strong upregulation of Tmem176a. While Tmem176b single-deficiency has no effect on the course of experimental autoimmune encephalomyelitis, T cell or DSS-induced colitis, it significantly reduces imiquimod-induced psoriasis-like skin inflammation. These findings shed light on a potentially novel specific process linked to post-Golgi trafficking for modulating the function of RORγt+ cells and indicate that both homologues should be simultaneously targeted to clearly elucidate the role of this intracellular ion flow.