Target Cell Expression of Suppressor of Cytokine Signaling-1 Prevents Diabetes in the NOD Mouse

Malin Flodström-Tullberg, Deepak Yadav, Robert Hägerkvist, Devin Tsai, Patrick Secrest, Alexandr Stotland, Nora Sarvetnick

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Although lymphocyte infiltration and islet destruction are hallmarks of diabetes, the mechanisms of β-cell destruction are not fully understood. One issue that remains unresolved is whether cytokines play a direct role in β-cell death. We investigated whether β-cell cytokine signaling contributes to autoimmune type 1 diabetes. We demonstrated that NOD mice harboring β-cells expressing the suppressor of cytokine signaling-1 (SOCS-1), an inhibitor of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling, have a markedly reduced incidence of diabetes. Similar to their non-transgenic (Tg) litter-mates, SOCS-1-Tg mice develop insulitis and their splenocytes transfer disease to NODscid recipients. Disease protection correlates with suppression of cytokine-induced STAT-1 phosphorylation in SOCS-1-expressing β-cells and with a reduced sensitivity of these cells to destruction by diabetogenic cells in vivo. Interestingly, lymphocytes recruited to the pancreas of SOCS-1-Tg mice transferred diabetes to NODscid recipients with a reduced efficiency, suggesting that the pancreatic environment in SOCS-1-Tg mice does not support the maintenance of functionally differentiated T-cells. These results suggest that cytokines contribute to the development of type 1 diabetes by acting directly on the target β-cell. Importantly, given that the SOCS-1-expressing mouse maintain normal blood glucose levels throughout life, this study also showed that SOCS-1 expression by β-cells can represent a promising strategy to prevent type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)2696-2700
Number of pages5
JournalDiabetes
Volume52
Issue number11
DOIs
StatePublished - Nov 1 2003

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Flodström-Tullberg, M., Yadav, D., Hägerkvist, R., Tsai, D., Secrest, P., Stotland, A., & Sarvetnick, N. (2003). Target Cell Expression of Suppressor of Cytokine Signaling-1 Prevents Diabetes in the NOD Mouse. Diabetes, 52(11), 2696-2700. https://doi.org/10.2337/diabetes.52.11.2696