Beta-cell specific expression of suppressor of cytokine signaling-1 (SOCS-1) delays islet allograft rejection by down-regulating Interferon Regulatory Factor-1 (IRF-1) signaling

Michelle Solomon, Malin Flodström-Tullberg, Nora E Sarvetnick

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We previously showed that targeted expression of SOCS-1 (Suppressor of Cytokine Signaling-1) to pancreatic beta cells (SOCS-1-transgenic (Tg) islets) from C57BL6/J mice delays islet allograft rejection in BALB/c mice. In the present study, we extend these observations to investigate the mechanism of this delayed rejection. We found that transgene expression of SOCS-1 rendered the islets significantly more resistant to cytokine-induced cell death after treatment with TNF-alpha alone and in combination with IFN-gamma. Furthermore, protection against cytokine-induced cytotoxicity correlated with significant inhibition of the transcription factor interferon regulatory factor-1 (IRF-1), reflecting enhanced cell survival signals. Moreover, we found that IFNg-induced class I MHC upregulation was significantly impaired in SOCS-1-Tg islets compared to non-Tg islets in the BALB/c host. Importantly, SOCS-1-Tg islets were able to reverse streptozotocin-induced diabetes for at least 2. weeks longer than normal islets. Our findings indicate that intra-graft expression of SOCS-1 renders islets insensitive to the deleterious effects of cytokines; this finding could be important in the development of therapies against acute allograft rejection.

Original languageEnglish (US)
Pages (from-to)181-188
Number of pages8
JournalTransplant Immunology
Volume24
Issue number3
DOIs
StatePublished - Apr 15 2011

Fingerprint

Interferon Regulatory Factor-1
Allografts
Cytokines
Experimental Diabetes Mellitus
Insulin-Secreting Cells
Transgenes
Cell Survival
Cell Death
Transcription Factors
Up-Regulation
Tumor Necrosis Factor-alpha
Transplants

Keywords

  • Cytokines
  • Cytotoxicity
  • Diabetes
  • MHC
  • Transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Transplantation

Cite this

Beta-cell specific expression of suppressor of cytokine signaling-1 (SOCS-1) delays islet allograft rejection by down-regulating Interferon Regulatory Factor-1 (IRF-1) signaling. / Solomon, Michelle; Flodström-Tullberg, Malin; Sarvetnick, Nora E.

In: Transplant Immunology, Vol. 24, No. 3, 15.04.2011, p. 181-188.

Research output: Contribution to journalArticle

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