التفاصيل البيبلوغرافية
| العنوان: |
Natural Variation in Interleukin-2 Sensitivity Influences Regulatory T-Cell Frequency and Function in Individuals With Long-standing Type 1 Diabetes. |
| المؤلفون: |
Yang, Jennie H. M., Cutler, Antony J., Ferreira, Ricardo C., Reading, James L., Cooper, Nicholas J., Wallace, Chris, Clarke, Pamela, Smyth, Deborah J., Boyce, Christopher S., Guo-Jian Gao, Todd, John A., Wicker, Linda S., Tree, Timothy I. M., Gao, Guo-Jian |
| المصدر: |
Diabetes; Nov2015, Vol. 64 Issue 11, p3891-3902, 12p, 1 Diagram, 7 Graphs |
| مصطلحات موضوعية: |
INTERLEUKIN-2, T cells, TYPE 1 diabetes, HOMEOSTASIS, GENETIC polymorphisms, IMMUNOTHERAPY, PHOSPHORYLATION, CELLULAR signal transduction, ESTERASES, RESEARCH funding, GENOTYPES, PHYSIOLOGY |
| مستخلص: |
Defective immune homeostasis in the balance between FOXP3+ regulatory T cells (Tregs) and effector T cells is a likely contributing factor in the loss of self-tolerance observed in type 1 diabetes (T1D). Given the importance of interleukin-2 (IL-2) signaling in the generation and function of Tregs, observations that polymorphisms in genes in the IL-2 pathway associate with T1D and that some individuals with T1D exhibit reduced IL-2 signaling indicate that impairment of this pathway may play a role in Treg dysfunction and the pathogenesis of T1D. Here, we have examined IL-2 sensitivity in CD4+ T-cell subsets in 70 individuals with long-standing T1D, allowing us to investigate the effect of low IL-2 sensitivity on Treg frequency and function. IL-2 responsiveness, measured by STAT5a phosphorylation, was a very stable phenotype within individuals but exhibited considerable interindividual variation and was influenced by T1D-associated PTPN2 gene polymorphisms. Tregs from individuals with lower IL-2 signaling were reduced in frequency, were less able to maintain expression of FOXP3 under limiting concentrations of IL-2, and displayed reduced suppressor function. These results suggest that reduced IL-2 signaling may be used to identify patients with the highest Treg dysfunction and who may benefit most from IL-2 immunotherapy. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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