期刊
JOURNAL OF IMMUNOLOGY
卷 207, 期 2, 页码 421-435出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2000498
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资金
- IHU-Cesti, Nantes Metropole
- Region des Pays de la Loire, Paris Scientifiques Regionaux (METABIMMUN)
- Agence Nationale de la Recherche (ANR) [ANR-11-LABX-0016-01, ANR-10-INBS-04]
- Fondation pour la Recherche Medicale (FRM) [ECO20160736078]
- CNRS
- FRM [DEQ20120323723]
- ANR [ANR-12-BSV2-0003-01]
- Labex CelTisPhyBio [11-LBX-0038]
- Idex Paris Sciences et Lettres [ANR-10-IDEX-0001-02PSL]
- Cell and Tissue Imaging Facility (PICT-IBiSA), Institut Curie [ANR10-INBS-04]
- Labex CellTisPhyBio
- Agence Nationale de la Recherche (ANR) [ANR-12-BSV2-0003] Funding Source: Agence Nationale de la Recherche (ANR)
This study investigated the role of TMEM176A/B in DCs and found that they are crucial for antigen processing and presentation to CD4(+) T cells, suggesting a direct role in the MHC class II compartment for fine regulation of antigen presentation and CD4(+) T cell priming.
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 gamma t(+) 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.
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