Transplantation of Aire-overexpressing bone marrow-derived dendritic cells delays the onset of type 1 diabetes |
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| Affiliation: | 1. Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China;2. Clinical Medical College of Jilin University, Changchun 130021, China;1. Infectivology and Clinical Trials Research Department, Children''s Hospital Bambino Gesù, Viale S. Paolo 15, 00146 Rome, Italy;2. Pediatric Immunology –Rheumatology, Uludag University, Medical Faculty Department of Pediatrics, Gorukle-Bursa 16059, Turkey;3. Endocrine Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy;1. Institute of Health Research-INCLIVA, Valencia, Spain;2. Endocrinology and Nutrition Department Hospital Clínico Universitario. Department of Medicine, University of Valencia, Valencia, Spain;3. CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain;4. Department of Pharmacology, University of Valencia, Valencia, Spain;5. Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain |
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| Abstract: | 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. |
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