STING deficiency promotes the development of autoimmune diabetes in NOD mice

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Abstract Summary

 

Type 1 diabetes is an autoimmune disease that results from autoreactive destruction of insulin producing beta cells and the pathogenesis is characterized by chronic infiltration of immune cells in islets. Stimulator of interferon genes (STING), is a central hub for cytosolic nucleic acid sensing in innate immunity and plays an important role in viral and tumor immunity. It was reported that gain-of-function mutations in STING cause systemic vasculitis with lupus-like manifestations in human, characterized by increased type I IFN production. An increased type I IFN gene signature has been reported in humans and NOD mice before the onset of type 1 diabetes, leading to the possibility that dysregulated type I IFN production via STING contributes to the development of autoimmunity. However, STING was also recently shown to have intrinsic anti-proliferative activity in T lymphocytes. We therefore tested whether STING may play a role in promoting or attenuating the progressive beta cell autoimmunity by generating NOD mice deficient in STING using Crispr/Cas9 editing technology. STING-deficient mice had a similar level of insulin autoantibodies when compared to wild-type NOD mice. Interestingly, accelerated diabetes was observed in STING-deficient mice. In accordance with this, STING-deficient NOD mice had increased frequency of beta cell antigen-specific T cells. T cell homeostasis and activation was not affected by STING deficiency. These data suggest that STING attenuates autoimmunity by controlling proliferation of beta cell-specific T cells, but does not contribute to generation of the type I IFN gene signature observed in NOD mice.

 

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IDS83165
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St. Vincent's Institute, Melbourne, Australia
St. Vincent's Institute, Melbourne, Australia
St Vincent's Institute of Medical Research
St. Vincent's Institute, Melbourne, Australia
St. Vincent's Institute, Melbourne, Australia
St Vincent's Institute of Medical Research
St Vincent's Institute of Medical Research
St Vincent's Institute of Medical Research

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Event dates:
Thursday 25 October - Monday 29 October 2018

Abstract submission deadline:
Monday 14 May 2018

Abstract notification:
July 2018

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Monday 3 September 2018

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Monday 15 October 2018

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