Dendritic Cells Require TMEM176A/B Ion Channels for Optimal MHC Class II Antigen Presentation to Naive CD4 + T Cells

Melanie Lancien (1, 2) , Geraldine Bienvenu (1, 2) , Sonia Salle (1, 2) , Lucile Gueno (1, 2) , Magalie Feyeux (2, 3) , Emmanuel Merieau (1, 2) , Severine Remy (1, 2) , Amandine Even (1, 2) , Aurelie Moreau (1, 2) , Alice Molle (1, 2) , Cynthia Fourgeux (1, 2) , Flora Coulon (1, 2) , Gaelle Beriou (1, 2) , Laurence Bouchet-Delbos (1, 2) , Elise Chiffoleau (1, 2) , Peggy Kirstetter (4) , Susan Chan (4) , Steven Kerfoot (5) , Saeed Abdu Rahiman (6) , Veronica de Simone (6) , Gianluca Matteoli (6) , Gaelle Boncompain (7) , Franck Perez (7) , Regis Josien (1, 2) , Jeremie Poschmann (1, 2) , Maria Cristina Cuturi (1, 2) , Cedric Louvet (1, 2)

1 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
2 CHU Nantes - Centre Hospitalier Universitaire de Nantes
3 SFR François Bonamy - Structure fédérative de recherche François Bonamy
4 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
5 UWO - University of Western Ontario
6 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
7 Biologie Cellulaire et Cancer

Intracellular ion fluxes emerge as critical actors of immunoregulation but still remain poorly explored. In this study, we investigated the role of the redundant cation channels TMEM176A and TMEM176B (TMEM176A/B) in retinoic acid-related orphan receptor γt+ cells and conventional dendritic cells (DCs) using germline and conditional double knockout mice. Although Tmem176a/b appeared surprisingly dispensable for the protective function of Th17 and group 3 innate lymphoid cells in the intestinal mucosa, we found that they were required in conventional DCs for optimal Ag processing and presentation to CD4+ T cells. Using a real-time imaging method, we show that TMEM176A/B accumulate in dynamic post-Golgi vesicles preferentially linked to the late endolysosomal system and strongly colocalize with HLA-DM. Taken together, our results suggest that TMEM176A/B ion channels play a direct role in the MHC class II compartment of DCs for the fine regulation of Ag presentation and naive CD4+ T cell priming.

Domaines: Immunologie

Melanie Lancien, Geraldine Bienvenu, Sonia Salle, Lucile Gueno, Magalie Feyeux, et al.. Dendritic Cells Require TMEM176A/B Ion Channels for Optimal MHC Class II Antigen Presentation to Naive CD4 + T Cells. Journal of Immunology, 2021, 207 (2), pp.421-435. ⟨10.4049/jimmunol.2000498⟩. ⟨hal-03449106⟩