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

• DOI: 10.4049/jimmunol.2000498
• Publication Date: 2021-07-07T17:56:38Z
• Authors: Melanie Lancien; Geraldine Bienvenu; Sonia Salle; Lucile Gueno; Magalie Feyeux; Emmanuel Merieau; Severine Remy; Amandine Even; Aurelie Moreau; Alice Molle; Cynthia Fourgeux; Flora Coulon; Gaelle Beriou; Laurence Bouchet-...; Elise Chiffoleau; Peggy Kirstetter; Susan Chan; Steven M Kerfoot; Saeed Abdu Rahiman; Veronica De Simone; Gianluca Matteoli; Gaelle Boncompain; Franck Perez; Regis Josien; Jeremie Poschmann; Maria Cristina Cu...; Cedric Louvet
• Keywords: CD4-Positive T-Lymphocytes; Male; 0301 basic medicine; 570; [SDV]Life Sciences [q-bio]; Genes, MHC Class II; 610; Golgi Apparatus; Endosomes; Ion Channels; Mice; 03 medical and health sciences; Animals; Lymphocytes; Intestinal Mucosa; Mice, Knockout; Antigen Presentation; Histocompatibility Antigens Class II; Membrane Proteins; Dendritic Cells; Immunity, Innate; Mice, Inbred C57BL; [SDV.IMM]Life Sciences [q-bio]/Immunology; Th17 Cells; Female; Lysosomes

Abstract 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.