Over-expression of Stat5b confers protection against diabetes in the non-obese diabetic (NOD) mice via up-regulation of CD4+CD25+ regulatory T cells

Yulan Jin, Sharad Purohit, Xueqin Chen, Bing Yi, Jin Xiong She

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The signal transducers and activators of transcription (STAT) family of proteins play a critical role in cytokine signaling required for fine tuning of immune regulation. Previous reports showed that a mutation (L327M) in the Stat5b protein leads to aberrant cytokine signaling in the NOD mice. To further elaborate the role of Stat5b in diabetes, we established a NOD transgenic mouse that over-expresses the wild type Stat5b gene. The incidences of spontaneous diabetes as well as cyclophosphamide-induced diabetes were significantly reduced and delayed in the Stat5b transgenic NOD mice compared to their littermate controls. The total cell numbers of CD4+ T cells and especially CD8+ T cells in the spleen and pancreatic lymph node were increased in the Stat5b transgenic NOD mice. Consistent with these findings, CD4+ and CD8+ T cells from the Stat5b transgenic NOD mice showed a higher proliferation capacity and up-regulation of multiple cytokines including IL-2, IFN-γ, TNF-α and IL-10 as well as anti-apoptotic gene Bcl-xl. Furthermore, the number and proportion of CD4+CD25+ regulatory T cells were significantly increased in transgenic mice although in vitro suppression ability of the regulatory T-cells was not affected by the transgene. Our results suggest that Stat5b confers protection against diabetes in the NOD mice by regulating the numbers and function of multiple immune cell types, especially by up-regulating CD4+CD25+ regulatory T cells.

Original languageEnglish (US)
Pages (from-to)669-674
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume424
Issue number4
DOIs
StatePublished - Aug 10 2012

Fingerprint

Inbred NOD Mouse
T-cells
Regulatory T-Lymphocytes
Medical problems
Up-Regulation
Transgenic Mice
Cytokines
T-Lymphocytes
Genes
STAT Transcription Factors
Transcription
Transgenes
Interleukin-10
Cyclophosphamide
Interleukin-2
Transducers
Proteins
Spleen
Tuning
Cell Count

Keywords

  • NOD
  • Regulatory T cells
  • Stat5b
  • Type-1 diabetes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

@article{ef538d786b814e10a2224722bc5b682b,
title = "Over-expression of Stat5b confers protection against diabetes in the non-obese diabetic (NOD) mice via up-regulation of CD4+CD25+ regulatory T cells",
abstract = "The signal transducers and activators of transcription (STAT) family of proteins play a critical role in cytokine signaling required for fine tuning of immune regulation. Previous reports showed that a mutation (L327M) in the Stat5b protein leads to aberrant cytokine signaling in the NOD mice. To further elaborate the role of Stat5b in diabetes, we established a NOD transgenic mouse that over-expresses the wild type Stat5b gene. The incidences of spontaneous diabetes as well as cyclophosphamide-induced diabetes were significantly reduced and delayed in the Stat5b transgenic NOD mice compared to their littermate controls. The total cell numbers of CD4+ T cells and especially CD8+ T cells in the spleen and pancreatic lymph node were increased in the Stat5b transgenic NOD mice. Consistent with these findings, CD4+ and CD8+ T cells from the Stat5b transgenic NOD mice showed a higher proliferation capacity and up-regulation of multiple cytokines including IL-2, IFN-γ, TNF-α and IL-10 as well as anti-apoptotic gene Bcl-xl. Furthermore, the number and proportion of CD4+CD25+ regulatory T cells were significantly increased in transgenic mice although in vitro suppression ability of the regulatory T-cells was not affected by the transgene. Our results suggest that Stat5b confers protection against diabetes in the NOD mice by regulating the numbers and function of multiple immune cell types, especially by up-regulating CD4+CD25+ regulatory T cells.",
keywords = "NOD, Regulatory T cells, Stat5b, Type-1 diabetes",
author = "Yulan Jin and Sharad Purohit and Xueqin Chen and Bing Yi and She, {Jin Xiong}",
year = "2012",
month = "8",
day = "10",
doi = "10.1016/j.bbrc.2012.06.162",
language = "English (US)",
volume = "424",
pages = "669--674",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - Over-expression of Stat5b confers protection against diabetes in the non-obese diabetic (NOD) mice via up-regulation of CD4+CD25+ regulatory T cells

AU - Jin, Yulan

AU - Purohit, Sharad

AU - Chen, Xueqin

AU - Yi, Bing

AU - She, Jin Xiong

PY - 2012/8/10

Y1 - 2012/8/10

N2 - The signal transducers and activators of transcription (STAT) family of proteins play a critical role in cytokine signaling required for fine tuning of immune regulation. Previous reports showed that a mutation (L327M) in the Stat5b protein leads to aberrant cytokine signaling in the NOD mice. To further elaborate the role of Stat5b in diabetes, we established a NOD transgenic mouse that over-expresses the wild type Stat5b gene. The incidences of spontaneous diabetes as well as cyclophosphamide-induced diabetes were significantly reduced and delayed in the Stat5b transgenic NOD mice compared to their littermate controls. The total cell numbers of CD4+ T cells and especially CD8+ T cells in the spleen and pancreatic lymph node were increased in the Stat5b transgenic NOD mice. Consistent with these findings, CD4+ and CD8+ T cells from the Stat5b transgenic NOD mice showed a higher proliferation capacity and up-regulation of multiple cytokines including IL-2, IFN-γ, TNF-α and IL-10 as well as anti-apoptotic gene Bcl-xl. Furthermore, the number and proportion of CD4+CD25+ regulatory T cells were significantly increased in transgenic mice although in vitro suppression ability of the regulatory T-cells was not affected by the transgene. Our results suggest that Stat5b confers protection against diabetes in the NOD mice by regulating the numbers and function of multiple immune cell types, especially by up-regulating CD4+CD25+ regulatory T cells.

AB - The signal transducers and activators of transcription (STAT) family of proteins play a critical role in cytokine signaling required for fine tuning of immune regulation. Previous reports showed that a mutation (L327M) in the Stat5b protein leads to aberrant cytokine signaling in the NOD mice. To further elaborate the role of Stat5b in diabetes, we established a NOD transgenic mouse that over-expresses the wild type Stat5b gene. The incidences of spontaneous diabetes as well as cyclophosphamide-induced diabetes were significantly reduced and delayed in the Stat5b transgenic NOD mice compared to their littermate controls. The total cell numbers of CD4+ T cells and especially CD8+ T cells in the spleen and pancreatic lymph node were increased in the Stat5b transgenic NOD mice. Consistent with these findings, CD4+ and CD8+ T cells from the Stat5b transgenic NOD mice showed a higher proliferation capacity and up-regulation of multiple cytokines including IL-2, IFN-γ, TNF-α and IL-10 as well as anti-apoptotic gene Bcl-xl. Furthermore, the number and proportion of CD4+CD25+ regulatory T cells were significantly increased in transgenic mice although in vitro suppression ability of the regulatory T-cells was not affected by the transgene. Our results suggest that Stat5b confers protection against diabetes in the NOD mice by regulating the numbers and function of multiple immune cell types, especially by up-regulating CD4+CD25+ regulatory T cells.

KW - NOD

KW - Regulatory T cells

KW - Stat5b

KW - Type-1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=84864802710&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864802710&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2012.06.162

DO - 10.1016/j.bbrc.2012.06.162

M3 - Article

C2 - 22789848

AN - SCOPUS:84864802710

VL - 424

SP - 669

EP - 674

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -