Expansion of Th17 cells and functional defects in T regulatory cells are key features of the pancreatic lymph nodes in patients with type 1 diabetes.
Expansion of Th17 cells and functional defects in T regulatory cells are key features of the pancreatic lymph nodes in patients with type 1 diabetes.
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DOI：
10.2337/db11-0090
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发表时间：
2011-11
期刊：
影响因子：
7.7
通讯作者：
Battaglia M
中科院分区：
文献类型：
--
作者：
Ferraro A;Socci C;Stabilini A;Valle A;Monti P;Piemonti L;Nano R;Olek S;Maffi P;Scavini M;Secchi A;Staudacher C;Bonifacio E;Battaglia M
自身免疫性疾病，包括 1 型糖尿病，被认为具有 Th17 细胞偏向和/或 T 调节细胞 (Treg) 缺陷。了解这是否是 1 型糖尿病患者的一个标志是一个尚未解决的关键问题，很大程度上是由于难以获取该疾病的目标组织。我们对 19 名 1 型糖尿病患者和 63 名非糖尿病供体的胰腺引流淋巴结 (PLN) 中以及 14 名 1 型糖尿病患者和 11 名健康受试者外周血中循环的 Th17 细胞和 Tregs 进行了表型和功能特征分析。我们发现 1 型糖尿病受试者的 PLN 中 Th17 免疫上调和 CD4+CD25bright Tregs 功能缺陷，但在他们的外周血中却没有。此外，糖尿病患者 PLN 中胰岛素原特异性 Treg 介导的控制发生了改变。从糖尿病受试者中分离出的功能失调的 Treg 不含有污染物效应 T 细胞，并且通过对叉头框 P3 (FOXP3) 基因座内 Treg 特异性去甲基化区域的分析来确定，这些 Treg 都具有抑制性的表观遗传印记。这些数据提供了 1 型糖尿病受试者 PLN 免疫状态不平衡的证据，恢复这些患者靶器官免疫稳态的治疗代表了一种潜在的治疗策略。
Autoimmune diseases, including type 1 diabetes, are thought to have a Th17-cell bias and/or a T-regulatory cell (Treg) defect. Understanding whether this is a hallmark of patients with type 1 diabetes is a crucial question that is still unsolved, largely due to the difficulties of accessing tissues targeted by the disease. We phenotypically and functionally characterized Th17 cells and Tregs residing in the pancreatic-draining lymph nodes (PLNs) of 19 patients with type 1 diabetes and 63 nondiabetic donors and those circulating in the peripheral blood of 14 type 1 diabetic patients and 11 healthy subjects. We found upregulation of Th17 immunity and functional defects in CD4+CD25bright Tregs in the PLNs of type 1 diabetic subjects but not in their peripheral blood. In addition, the proinsulin-specific Treg-mediated control was altered in the PLNs of diabetic patients. The dysfunctional Tregs isolated from diabetic subjects did not contain contaminant effector T cells and were all epigenetically imprinted to be suppressive, as defined by analysis of the Treg-specific demethylated region within the forkhead box P3 (FOXP3) locus. These data provide evidence for an unbalanced immune status in the PLNs of type 1 diabetic subjects, and treatments restoring the immune homeostasis in the target organ of these patients represent a potential therapeutic strategy.