RORγt+ cells selectively express redundant cation channels linked to the Golgi apparatus

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Drujont, Lucile | Lemoine, Aurélie | Moreau, Aurélie | Bienvenu, Géraldine | Lancien, Mélanie | Cens, Thierry | Guillot, Flora | Bériou, Gaëlle | Bouchet-Delbos, Laurence | Fehling, Hans, Jörg | Chiffoleau, Elise | Nicot, Arnaud, B | Charnet, Pierre | Martin, Jérôme, C | Josien, Régis | Cuturi, Maria, Cristina | Louvet, Cédric

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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