The type 1 diabetes resistance locus B10 Idd9.3 mediates impaired B-cell lymphopoiesis and implicates microRNA-34a in diabetes protection

摘要: NOD.B10 Idd9.3 mice are congenic for the insulin-dependent diabetes (Idd) locus, which confers significant type 1 (T1D) protection and encodes 19 genes, including microRNA (miR)-34a, from T1D-resistant C57BL/10 mice. B cells have been shown to play a critical role in priming of autoantigen-specific CD4(+) T T1D pathogenesis non-obese diabetic (NOD) We show that early B-cell development is impaired mice, resulting profound reduction transitional mature splenic as compared with NOD Molecular analysis revealed miR-34a expression was significantly higher progenitors marginal zone than Furthermore, these cell populations inversely correlated levels Foxp1, an essential regulator lymphopoiesis, directly repressed by miR-34a. In addition, we islet-specific proliferated inefficiently when primed vitro or response endogenous autoantigen Thus, Idd9.3-encoded likely candidate negatively regulating may contribute inefficient expansion