PuSH - Publication Server of Helmholtz Zentrum München

Monti, P.* ; Brigatti, C.* ; Krasmann, M. ; Ziegler, A.-G. ; Bonifacio, E.*

Concentration and activity of the soluble form of the interleukin-7 receptor α in type I diabetes identifies an interplay between hyperglycemia and immune function.

Diabetes 62, 2500-2508 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Soluble IL-7 receptor alpha (sCD127) is implicated in the pathogenesis of autoimmune diseases. We show that serum sCD127 concentrations are increased at the onset of type 1 diabetes (n=390) as compared to concentrations in age-matched islet autoantibody negative first degree relatives of patients (n=392; P=0.00001). sCD127 Concentration in patients was influenced by islet autoantibody status (P=0.003) and genotype of the rs6897932 single nucleotide polymorphism within theIL-7RA gene (P=0.006). Release of sCD127 in vitro was strongly up-regulated by activation of T lymphocytes, and affected by exposure to cytokines. sCD127 bound IL-7 and was antagonistic to IL-7 signaling and IL-7 mediated T cell proliferation suggesting a regulatory feedback mechanism on T cell expansion. Remarkably, high glucose led to a glycated form of sCD127 that was ineffective as an IL-7 antagonist. The finding of glycated sCD127 in the circulation of patients at onset of type 1 diabetes suggested that physiological regulation of IL-7 mediated T cell survival and expansion by sCD127 may be compromised in type 1 diabetes. The findings indicate that genetic, immunologic and metabolic factors contribute to a dysregulation of the IL-7/IL-7 receptor pathway in type 1 diabetes, and identify a novel hyperglycemia mediated interference of immune regulatory networks.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Keywords Cd4 T-cells ; Multiple-sclerosis ; In-vivo ; Expression ; Il-7 ; Autoimmunity ; Associations ; Haplotypes ; Humans ; Design
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 62, Issue: 7, Pages: 2500-2508 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research (IDF)
Institute of Pancreatic Islet Research (IPI)