Transplantation of Aire-overexpressing bone marrow-derived dendritic cells delays the onset of type 1 diabetes

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Autoimmune regulator (Aire) plays an indispensable role in maintaining central immune tolerance by promoting the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), which lead to the deletion of autoreactive T cells or the induction of Tregs and consequently prevent autoimmune disease development. Curing autoimmune diseases has always been a challenge. DC-based immunotherapy represents a new and effective method to establish tolerance. We attempted to transplant Aire-overexpressing bone marrow-derived DCs (Aire-BMDCs) to treat type 1 diabetes (T1D) and to explore a new strategy for autoimmune disease treatment. We observed that the onset of T1D in recipient mice was delayed; insulin autoantibody (IAA) production was significantly decreased; the structure of islets was protected; and the degree of inflammatory infiltration was lower. Furthermore, we found that Aire-BMDCs can promote apoptosis and induce autoreactive CD4+ T cell clonal anergy, inhibit Th1 and Th17 production, and induce Treg production. These results suggest that transplantation of Aire-BMDCs will be a manipulation and effective method for preventing or treating T1D.Graphical abstractHighlightsWe explored a new strategy for type 1 diabetes treatment by Aire gene transduction and bone marrow dendritic cells transplantation.Aire-overexpressing BMDCs regulate the expression of many TRAs and provide advantages to solve the epitope spreading of self-antigens during the course of autoimmune disease.Aire-overexpressing BMDCs can remove antigen-specific T cells to a great extent and induce Treg, resulting in immune tolerance.This therapy targeting self-antigens specifically does not affect the normal body response to pathogens.

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