Aims
Type 1 diabetes, as a kind of autoimmune diseases, usually
Conclusions
These results provide an experimental basis for comprehensively elucidating the role and significance of Aire expression in peripheral DCs, thereby providing new ideas for the treatment of autoimmune diseases by using Aire as a target to induce the production of perforin-expressing DCs.
Methods
We conducted studies based on the Aire-overexpressing bone marrow-derived dendritic cell (BMDC) model. And through in vitro and in vivo experiments to observe that Aire-overexpressing BMDCs which express perforin induce immune tolerance and treat type 1 diabetes via TLR7/8.
Results
Aire enhances the expression of perforin in BMDCs after treatment with the TLR7/8 ligand as well as promotes the expression of TLR7/8 and myeloid differentiation primary response gene 88 (MyD88)-dependent pathway molecules. Aire-overexpressing BMDCs mediate apoptosis of allogeneic CD8+ T cells via perforin in vitro. Moreover, Aire-overexpressing BMDCs enhance the therapeutic effect of type 1 diabetes in non-obese diabetic (NOD) mice via perforin and induce apoptosis of autoreactive CD8+ T cells in vivo. Conclusions: These results provide an experimental basis for comprehensively elucidating the role and significance of Aire expression in peripheral DCs, thereby providing new ideas for the treatment of autoimmune diseases by using Aire as a target to induce the production of perforin-expressing DCs.