Differential expression of CC chemokines and the CCR5 receptor in the pancreas is associated with progression to type I diabetes
Differential expression of CC chemokines and the CCR5 receptor in the pancreas is associated with progression to type I diabetes
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DOI：
10.4049/jimmunol.165.2.1102
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发表时间：
2000-07-15
影响因子：
4.4
通讯作者：
Delovitch, TL
中科院分区：
文献类型：
--
作者：
Cameron, MJ;Arreaza, GA;Delovitch, TL
我们研究了CC趋化因子在Th1介导的非肥胖糖尿病(NOD)小鼠自发性I型糖尿病发病机制中的生物学作用。在NOD小鼠中，胰腺中巨噬细胞炎性蛋白-1α(MIP-1α)：MIP-1β的比率升高与破坏性胰岛素炎和进展为糖尿病相关，而在非肥胖糖尿病抵抗(NOR)小鼠中观察到胰腺内MIP-1α：MIP-1β的比率降低。IL-4治疗通过极化胰岛内Th2反应来预防NOD小鼠的糖尿病，减少胰岛CCR5的表达，并增强胰腺中高比例的MIP-1β和单核细胞趋化蛋白-1(MCP-1)：MIP-1α。此外，NOD.MIP-1α(-/-)小鼠的破坏性胰岛素炎减少，并受到糖尿病的保护。在NOD、SCID受者中，在转移糖尿病T细胞后，用特定抗体中和MIP-1a可延迟糖尿病的发生。这些研究表明，某些CC趋化因子，特别是MIP-1α和CCR5趋化因子受体在胰腺中的瞬时表达与胰岛素炎和自发性I型糖尿病的发生有关。
We investigated the biological role of CC chemokines in the Th1-mediated pathogenesis of spontaneous type I diabetes in nonobese diabetic (NOD) mice. Whereas an elevated ratio of macrophage inflammatory protein-1 alpha (MIP-1 alpha):MIP-1 beta in the pancreas correlated with destructive insulitis and progression to diabetes in NOD mice, a decreased intrapancreatic MIP-1 alpha:MIP-1 beta ratio was observed in nonobese diabetes-resistant (NOR) mice. IL-4 treatment, which prevents diabetes in NOD mice by polarizing intraislet Th2 responses, decreased CCR5 expression in islets and potentiated a high ratio of MIP-1 beta and monocyte chemotactic protein-1 (MCP-1): MIP-1 alpha in the pancreas. Furthermore, NOD.MIP-1 alpha(-/-) mice exhibited reduced destructive insulitis and were protected from diabetes. Neutralization of MIP-la with specific Abs following transfer of diabetogenic T cells delayed the onset of diabetes in NOD,Scid recipients. These studies illustrate that the temporal expression of certain CC chemokines, particularly MIP-1 alpha, and the CCR5 chemokine receptor in the pancreas is associated with the development of insulitis and spontaneous type I diabetes.