| Alterations of peripheral CD4(+)CD25(+)Foxp3(+) T regulatory cells in mice with STZ-induced diabetes. | |
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MedLine Citation:
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PMID: 21983870 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Complications arising from abnormal immune responses are the major causes of mortality and morbidity in diabetic patients. CD4(+)CD25(+) T regulatory cells (Tregs) play pivotal roles in controlling immune homeostasis, immunity and tolerance. The effect of hyperglycemia on CD4(+)CD25(+) Tregs has not yet been addressed. Here we used streptozotocin (STZ)-induced diabetic mice to study the effects of long-term hyperglycemia on CD4(+)CD25(+) Tregs in vivo. Four months after the onset of diabetes, the frequency of CD4(+)CD25(+)Foxp3(+) T regulatory cells was significantly elevated in the spleen, peripheral blood lymphocytes (PBLs), peripheral lymph nodes (pLNs) and mesenteric LNs (mLNs). CD4(+)CD25(+) Tregs obtained from mice with diabetes displayed defective immunosuppressive functions and an activated/memory phenotype. Insulin administration rescued these changes in the CD4(+)CD25(+) Tregs of diabetic mice. The percentage of thymic CD4(+)CD25(+) naturally occurring Tregs (nTregs) and peripheral CD4(+)Helios(+)Foxp3(+) nTregs were markedly enhanced in diabetic mice, indicating that thymic output contributed to the increased frequency of peripheral CD4(+)CD25(+) Tregs in diabetic mice. In an in vitro assay in which Tregs were induced from CD4(+)CD25(-) T cells by transforming growth factor (TGF)-β, high glucose enhanced the efficiency of CD4(+)CD25(+)Foxp3(+) inducible Tregs (iTregs) induction. In addition, CD4(+)CD25(-) T cells from diabetic mice were more susceptible to CD4(+)CD25(+)Foxp3(+) iTreg differentiation than those cells from control mice. These data, together with the enhanced frequency of CD4(+)Helios(-)Foxp3(+) iTregs in the periphery of mice with diabetes, indicate that enhanced CD4(+)CD25(+)Foxp3(+) iTreg induction also contributes to a peripheral increase in CD4(+)CD25(+) Tregs in diabetic mice. Our data show that hyperglycemia may alter the frequency of CD4(+)CD25(+)Foxp3(+) Tregs in mice, which may result in late-state immune dysfunction in patients with diabetes.Cellular & Molecular Immunology advance online publication, 10 October 2011; doi:10.1038/cmi.2011.37. |
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Authors:
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Yu Zhen; Lina Sun; He Liu; Kaizhong Duan; Chun Zeng; Lianjun Zhang; Di Jin; Jianxia Peng; Wenjun Ding; Yong Zhao |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-10 |
Journal Detail:
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Title: Cellular & molecular immunology Volume: - ISSN: 2042-0226 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101242872 Medline TA: Cell Mol Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China [2] College of Life Sciences, Graduate University of the Chinese Academy of Sciences, Beijing, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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