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The Intracellular Ion flux mediated by TMEM176A and TMEM176B is involved in the regulation of Dendritic Cell Functions

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Lancien, Mélanie | Bienvenu-Louvet, Géraldine | Guéno, Lucile | Moreau, Aurélie | Salle, Sonia | Merieau, Emmanuel | Bouchet-Delbos, Laurence | Coulon, Flora | Boncompain, Gaëlle | Perez, Franck | Cuturi, Maria, Cristina | Louvet, Cédric

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International audience. The regulation of immune cells by intracellular ion channels remains poorly explored. Here we investigated the role of two cation channels encoded by Tmem176a and Tmem176b that are highly expressed in myeloid cells in the immune system. To avoid any functional compensation, we generated double knock-out (DKO) mice, allowing simultaneous deletion of these two highly redundant and coregulated genes using the CRISPR-Cas9 system. The absence of Tmem176a/b significantly impacted antigen processing and presentation to CD4+ T cells in vivo and selectively altered cytokine production by dendritic cells (DCs). Using a novel 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. Thus, these results highlight the importance of TMEM176A/B-mediated cation flux for the fine regulation of DC biology.

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