ROR?t+ cells selectively express redundant cation channels linked to the Golgi apparatus.

ABSTRACT: Retinoid-related orphan receptor gamma t (ROR?t) 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 ?? T cells. Here we show that the intracellular ion channel TMEM176B and its homologue TMEM176A are strongly expressed in these ROR?t(+) 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 ROR?t(+) cells and indicate that both homologues should be simultaneously targeted to clearly elucidate the role of this intracellular ion flow.

SUBMITTER: Drujont L 

PROVIDER: S-EPMC4806298 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature