Other - Immunoregulation
Ion channels represent attractive targets for the development of new therapies but still remain poorly studied in the immune system, in particular intracellular ion channels. In this work, we explored the role of two highly redundant ion channels named TMEM176A and TMEM176B that are intriguingly strongly expressed both in RORγt+ cells (ILC3, Th17) and immature dendritic cells. To investigate the role of these homologs and avoid any compensation effect, we generated a double KO (DKO) mouse using CRISPR-Cas9. Surprisingly, Tmem176a/b appeared dispensable for the function of RORγt+ cells and in the protective function of type 17 immunity during chemically-induced or infectious colitis. In contrast, antigen presentation by dendritic cells to CD4+ T cells through MHC II was selectively impaired in DKO mice. Using a real-time fluorescence-based system to analyze intracellular trafficking we found that both channels co-localized in highly dynamic post-Golgi vesicles preferentially interacting with, but not accumulating in, acidic organelles. These results indicate that TMEM176A/B ion channels play a predominant role in adaptive immunity as new intracellular components of the intracellular MHC II machinery.