Dendritic Cells Require TMEM176A/B Ion Channels for Optimal MHC Class II Antigen Presentation to Naive CD4 + T Cells

J Immunol. 2021 Jul 15;207(2):421-435. doi: 10.4049/jimmunol.2000498. Epub 2021 Jul 7.

Abstract

Intracellular ion fluxes emerge as critical actors of immunoregulation but still remain poorly explored. In this study, we investigated the role of the redundant cation channels TMEM176A and TMEM176B (TMEM176A/B) in retinoic acid-related orphan receptor γt+ cells and conventional dendritic cells (DCs) using germline and conditional double knockout mice. Although Tmem176a/b appeared surprisingly dispensable for the protective function of Th17 and group 3 innate lymphoid cells in the intestinal mucosa, we found that they were required in conventional DCs for optimal Ag 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. Taken together, our results suggest that TMEM176A/B ion channels play a direct role in the MHC class II compartment of DCs for the fine regulation of Ag presentation and naive CD4+ T cell priming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Dendritic Cells / immunology*
  • Endosomes / immunology
  • Female
  • Genes, MHC Class II / immunology
  • Golgi Apparatus / immunology
  • Histocompatibility Antigens Class II / immunology*
  • Immunity, Innate / immunology
  • Intestinal Mucosa / immunology
  • Ion Channels / immunology
  • Lymphocytes / immunology
  • Lysosomes / immunology
  • Male
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Th17 Cells / immunology
  • Tretinoin / immunology

Substances

  • Histocompatibility Antigens Class II
  • Ion Channels
  • Membrane Proteins
  • Tmem176A protein, mouse
  • Tmem176B protein, mouse
  • Tretinoin