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- W1543497746 abstract "The administration of autologous (recipient-derived) tolerogenic dendritic cells (ATDCs) is under clinical evaluation. However, the molecular mechanisms by which these cells prolong graft survival in a donor-specific manner is unknown. Here, we tested mouse ATDCs for their therapeutic potential in a skin transplantation model. ATDC injection in combination with anti-CD3 treatment induced the accumulation of CD8(+) CD11c(+) T cells and significantly prolonged allograft survival. TMEM176B is an intracellular protein expressed in ATDCs and initially identified in allograft tolerance. We show that Tmem176b(-/-) ATDCs completely failed to trigger both phenomena but recovered their effect when loaded with donor peptides before injection. These results strongly suggested that ATDCs require TMEM176B to cross-present antigens in a tolerogenic fashion. In agreement with this, Tmem176b(-/-) ATDCs specifically failed to cross-present male antigens or ovalbumin to CD8(+) T cells. Finally, we observed that a Tmem176b-dependent cation current controls phagosomal pH, a critical parameter in cross-presentation. Thus, ATDCs require TMEM176B to cross-present donor antigens to induce donor-specific CD8(+) CD11c(+) T cells with regulatory properties and prolong graft survival." @default.
- W1543497746 created "2016-06-24" @default.
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- W1543497746 date "2014-05-01" @default.
- W1543497746 modified "2023-10-18" @default.
- W1543497746 title "Autologous Dendritic Cells Prolong Allograft Survival Through Tmem176b-Dependent Antigen Cross-Presentation" @default.
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- W1543497746 doi "https://doi.org/10.1111/ajt.12708" @default.
- W1543497746 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4629416" @default.
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