Transplantation of Aire-overexpressing bone marrow-derived dendritic cells delays the onset of type 1 diabetes
Transplantation of Aire-overexpressing bone marrow-derived dendritic cells delays the onset of type 1 diabetes
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移植过度表达 Aire 的骨髓源性树突状细胞可延缓 1 型糖尿病的发病
DOI：
10.1016/j.intimp.2017.05.023
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发表时间：
2017-08-01
影响因子：
5.6
通讯作者：
Li, Yi
中科院分区：
文献类型：
--
作者：
Li, Dongbei;Zhao, Bo;Li, Yi
自身免疫调节剂（Aire）通过促进胸腺髓样上皮细胞（mTECs）和树突状细胞（dc）中组织限制性抗原（TRAs）的异位表达，导致自身反应性T细胞的缺失或Tregs的诱导，从而在维持中枢免疫耐受中发挥不可或缺的作用，从而防止自身免疫性疾病的发展。治疗自身免疫性疾病一直是一个挑战。基于dc的免疫治疗是一种新的、有效的建立耐受性的方法。我们尝试移植air -过表达的骨髓源性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，受体小鼠的T1D发病延迟；胰岛素自身抗体（IAA）产生显著降低；小岛的结构得到了保护；炎症浸润程度较低。此外，我们发现Aire-BMDCs可以促进细胞凋亡，诱导自身反应性CD4(+) T细胞克隆能量，抑制Thl和Th17的产生，诱导Treg的产生。这些结果表明，Aire-BMDCs移植将是预防或治疗T1D的一种有效方法。
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 Thl 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.