 |
Journal articles
Autologous Dendritic Cells Prolong Allograft Survival Through Tmem176b-Dependent Antigen Cross-Presentation
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.
Cited literature [51 references]
https://www.hal.inserm.fr/inserm-02167834
Contributor : Sylvie Le Bihan <>
Submitted on : Friday, June 28, 2019 - 11:11:55 AM
Last modification on : Tuesday, July 21, 2020 - 3:58:30 AM
Contributor : Sylvie Le Bihan <>
Submitted on : Friday, June 28, 2019 - 11:11:55 AM
Last modification on : Tuesday, July 21, 2020 - 3:58:30 AM
File
emss-65580.pdf
Publisher files allowed on an open archive