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1 型糖尿病患者胰腺淋巴结中 Th17 细胞的扩增和 T 调节细胞的功能缺陷是其主要特征。

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.

机构信息

Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy.

出版信息

Diabetes. 2011 Nov;60(11):2903-13. doi: 10.2337/db11-0090. Epub 2011 Sep 6.

DOI:10.2337/db11-0090
PMID:21896932
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3198077/
Abstract

OBJECTIVE

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.

RESEARCH DESIGN AND METHODS

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.

RESULTS

We found upregulation of Th17 immunity and functional defects in CD4(+)CD25(bright) 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.

CONCLUSIONS

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.

摘要

目的

自身免疫性疾病，包括 1 型糖尿病，被认为存在 Th17 细胞偏向和/或 T 调节细胞（Treg）缺陷。了解这是否是 1 型糖尿病患者的特征是一个关键问题，但尚未得到解决，主要是因为难以获得针对该疾病的组织。

研究设计和方法

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 名健康受试者的外周血中存在的 Th17 细胞和 Treg 进行了表型和功能特征分析。

结果

我们发现 1 型糖尿病患者的 PLN 中 Th17 免疫上调和 CD4(+)CD25(bright)Treg 功能缺陷，但在外周血中没有。此外，糖尿病患者的 PLN 中胰岛素原特异性 Treg 介导的控制发生改变。从糖尿病患者中分离出的功能失调的 Treg 不含有污染的效应 T 细胞，并且根据叉头框 P3（FOXP3）基因座内 Treg 特异性去甲基化区域的分析，所有的 Treg 都被表观遗传印记为具有抑制作用。

结论

这些数据为 1 型糖尿病患者的 PLN 中存在不平衡的免疫状态提供了证据，恢复这些患者靶器官中免疫平衡的治疗方法代表了一种潜在的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b018/3198077/d3683fcd80b5/2903fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b018/3198077/0f44e9f16ade/2903fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b018/3198077/5f080106b1d8/2903fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b018/3198077/dc1ac90aaa5d/2903fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b018/3198077/01a15696da2d/2903fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b018/3198077/214e951fa90e/2903fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b018/3198077/d3683fcd80b5/2903fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b018/3198077/0f44e9f16ade/2903fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b018/3198077/5f080106b1d8/2903fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b018/3198077/dc1ac90aaa5d/2903fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b018/3198077/01a15696da2d/2903fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b018/3198077/214e951fa90e/2903fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b018/3198077/d3683fcd80b5/2903fig6.jpg

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