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首页> 外文期刊>The journal of clinical investigation >Prevention of murine autoimmune diabetes by CCL22-mediated Treg recruitment to the pancreatic islets
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Prevention of murine autoimmune diabetes by CCL22-mediated Treg recruitment to the pancreatic islets

机译：通过CCL22介导的Treg募集到胰岛来预防鼠类自身免疫性糖尿病

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摘要

Type 1 diabetes is characterized by destruction of insulin-producing β cells in the pancreatic islets by effector T cells. Tregs, defined by the markers CD4 and FoxP3, regulate immune responses by suppressing effector T cells and are recruited to sites of action by the chemokine CCL22. Here, we demonstrate that production of CCL22 in islets after intrapancreatic duct injection of double-stranded adeno-associated virus encoding CCL22 recruits endogenous Tregs to the islets and confers long-term protection from autoimmune diabetes in NOD mice. In addition, adenoviral expression of CCL22 in syngeneic islet transplants in diabetic NOD recipients prevented β cell destruction by autoreactive T cells and thereby delayed recurrence of diabetes. CCL22 expression increased the frequency of Tregs, produced higher levels of TGF-β in the CD4~(+) T cell population near islets, and decreased the frequency of circulating autoreactive CD8~(+) T cells and CD8~(+) IFN-γ–producing T cells. The protective effect of CCL22 was abrogated by depletion of Tregs with a CD25-specific antibody. Our results indicate that islet expression of CCL22 recruits Tregs and attenuates autoimmune destruction of β cells. CCL22-mediated recruitment of Tregs to islets may be a novel therapeutic strategy for type 1 diabetes.
机译：1型糖尿病的特征是效应T细胞破坏胰岛中产生胰岛素的β细胞。由标记CD4和FoxP3定义的Treg通过抑制效应T细胞来调节免疫反应，并被趋化因子CCL22募集到作用位点。在这里，我们证明胰管内注射编码CCL22的双链腺相关病毒后胰岛中CCL22的产生将内源性Treg募集到胰岛，并赋予NOD小鼠长期免于自身免疫性糖尿病的保护。另外，在糖尿病性NOD受体的同基因胰岛移植物中，CCL22的腺病毒表达阻止了自身反应性T细胞对β细胞的破坏，从而延迟了糖尿病的复发。 CCL22表达增加了Tregs的频率，在胰岛附近的CD4〜（+）T细胞群体中产生了较高水平的TGF-β，并降低了循环自身反应性CD8〜（+）T细胞和CD8〜（+）IFN-α的频率。产生γ的T细胞。通过用CD25特异性抗体消除Treg，可以消除CCL22的保护作用。我们的结果表明，CCL22的胰岛表达募集了Treg，并减弱了β细胞的自身免疫破坏。 CCL22介导的Treg募集到胰岛可能是1型糖尿病的新治疗策略。

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