Open Access Green as soon as Postprint is submitted to ZB.
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.
Diabetes 60, 2903-2913 (2011)
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.
Impact Factor
Scopus SNIP
Scopus
Cited By
Cited By
Altmetric
0.000
2.055
152
Annotations
Special Publikation
Hide on homepage
Publication type
Article: Journal article
Document type
Scientific Article
Language
english
Publication Year
2011
HGF-reported in Year
0
ISSN (print) / ISBN
0012-1797
e-ISSN
1939-327X
Journal
Diabetes
Quellenangaben
Volume: 60,
Issue: 11,
Pages: 2903-2913
Publisher
American Diabetes Association
Publishing Place
Alexandria, VA.
Reviewing status
Peer reviewed
Institute(s)
Institute of Pancreatic Islet Research (IPI)
PubMed ID
21896932
Erfassungsdatum
2011-12-31