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Dendritic cells require TMEM176A/B ion channels for optimal MHC II antigen presentation to naive CD4 + T cells

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Lancien, Mélanie | Bienvenu, Géraldine | Guéno, Lucile | Merieau, Emmanuel | Remy, Severine | Even, Amandine | Moreau, Aurelie | Molle, Alice | Fourgeux, Cynthia, Jaeger | Coulon, Flora | Bériou, Gaelle | Bouchet-Delbos, Laurence | Chiffoleau, Elise | Kirstetter, Peggy | Chan, Susan | Kerfoot, Steven | Abdu Rahiman, Saeed | de Simone, Veronica | Matteoli, Gianluca | Boncompain, Gaëlle | Perez, Franck | Josien, Régis | Poschmann, Jérémie | Cuturi, Maria Cristina | Louvet, Cédric

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Intracellular ion fluxes emerge as critical actors of immunoregulation but still remain poorly explored. Here we investigated the role of the redundant cation channels TMEM176A and TMEM176B (TMEM176A/B) in RORγt + cells and conventional dendritic cells (cDCs) using germline and conditional double knock-out (DKO) mice. While Tmem176a/b appeared surprisingly dispensable for the protective function of Th17 and group 3 innate lymphoid cells (ILC3s) in the intestinal mucosa, we found that they were required in cDCs for optimal antigen 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. Together, our results suggest that TMEM176A/B ion channels play a direct role in the MHC II compartment (MIIC) of DCs for the fine regulation of antigen presentation and naive CD4 + T cell priming.

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