Li Dongbei, Zhao Bo, Luo Yadong, Limbara Steven, Zhao Bingjie, Zou Xueyang, Yang Wei, Li Yi
Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China.
Clinical Medical College of Jilin University, Changchun 130021, China.
Int Immunopharmacol. 2017 Aug;49:13-20. doi: 10.1016/j.intimp.2017.05.023. Epub 2017 May 24.
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.
自身免疫调节因子（Aire）通过促进组织限制性抗原（TRA）在胸腺髓质上皮细胞（mTEC）和树突状细胞（DC）中的异位表达，在维持中枢免疫耐受方面发挥着不可或缺的作用，这会导致自身反应性T细胞的清除或调节性T细胞（Treg）的诱导，从而预防自身免疫性疾病的发展。治愈自身免疫性疾病一直是一项挑战。基于DC的免疫疗法是一种建立耐受性的新的有效方法。我们试图移植过表达Aire的骨髓来源的DC（Aire-BMDC）来治疗1型糖尿病（T1D），并探索一种治疗自身免疫性疾病的新策略。我们观察到受体小鼠中T1D的发病延迟；胰岛素自身抗体（IAA）的产生显著减少；胰岛结构得到保护；炎症浸润程度较低。此外，我们发现Aire-BMDC可以促进细胞凋亡并诱导自身反应性CD4 T细胞克隆无能，抑制Th1和Th17的产生，并诱导Treg的产生。这些结果表明，移植Aire-BMDC将是预防或治疗T1D的一种有效方法。
