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

Lancien, M.; Bienvenu, G.; Gueno, L.; Salle, S.; Merieau, E.; Remy, S.; Even, A.; Moreau, A.; Molle, A.; Fourgeux, C.; Coulon, F.; Beriou, G.; Bouchet-Delbos, L.; Chiffoleau, E.; Kirstetter, P.; Chan, S.; Kerfoot, S.; Abdu Rahiman, S.; De Simone, V.; Matteoli, G.; Boncompain, G.; Perez, F.; Josien, R.; Poschmann, J.; Cuturi, M. C.; Louvet, C.

2019-11-22 immunology
10.1101/851527 bioRxiv
Show abstract

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 ROR{gamma}t+ 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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