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.

doi:10.1101/851527

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bioRxiv · 10.1101/851527

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

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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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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. Dendritic cells require TMEM176A/B ion channels for optimal MHC II antigen presentation to naive CD4+ T cells. https://doi.org/10.1101/851527

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