title: RORγt+ cells selectively express redundant cation channels linked to the Golgi apparatus.
abstract: 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.
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Drujont
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Lemoine
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Moreau
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Bienvenu
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Lancien
authors.affiliation: CNRS UMR 5237, CRBM, 34293 Montpellier, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Cens
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.
authors.forename: Flora
authors.initials: F
authors.lastname: Guillot
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Bériou
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bouchet-Delbos
authors.affiliation: Institute of Immunology, University Clinics Ulm, 8901 Ulm, Germany.
authors.forename: Hans Jörg
authors.initials: HJ
authors.lastname: Fehling
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Chiffoleau
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.
authors.forename: Arnaud B
authors.initials: AB
authors.lastname: Nicot
authors.affiliation: CNRS UMR 5237, CRBM, 34293 Montpellier, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Charnet
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.|Faculté de Médecine, Université de Nantes, 44093 Nantes, France.|Laboratoire d'Immunologie, CHU Nantes, 44093 Nantes, France.
authors.forename: Jérôme C
authors.initials: JC
authors.lastname: Martin
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.|Faculté de Médecine, Université de Nantes, 44093 Nantes, France.|Laboratoire d'Immunologie, CHU Nantes, 44093 Nantes, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Josien
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Cuturi
authors.affiliation: INSERM UMR 1064, Center for Research in Transplantation and Immunology; Université de Nantes; CHU Nantes, Institut de Transplantation Urologie Néphrologie (ITUN); 44093 Nantes, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Louvet
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D011565:Psoriasis / Q000139:chemically induced / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000378:metabolism; D021601:trans-Golgi Network / Q000235:genetics / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C000613738:TMEM176A protein, human; C000613739:TMEM176B protein, human; C552365:Tmem176A protein, mouse; C552366:Tmem176B protein, mouse