| Autor: |
Satoru, Akazawa, Leanne, Mackin, Gaurang, Jhala, Stacey, Fynch, Tara, Catterall, Claudia, Selck, Kate L, Graham, Balasubramanian, Krishnamurthy, Evan G, Pappas, Chun-Ting J, Kwong, Andrew P R, Sutherland, Thomas W H, Kay, Thomas C, Brodnicki, Helen E, Thomas |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Diabetologia. 64(4) |
| ISSN: |
1432-0428 |
| Popis: |
Stimulator of IFN genes (STING) is a central hub for cytosolic nucleic acid sensing and its activation results in upregulation of type I IFN production in innate immune cells. A type I IFN gene signature seen before the onset of type 1 diabetes has been suggested as a driver of disease initiation both in humans and in the NOD mouse model. A possible source of type I IFN is through activation of the STING pathway. Recent studies suggest that STING also has antiproliferative and proapoptotic functions in T cells that are independent of IFN. To investigate whether STING is involved in autoimmune diabetes, we examined the impact of genetic deletion of STING in NOD mice.CRISPR/Cas9 gene editing was used to generate STING-deficient NOD mice. Quantitative real-time PCR was used to assess the level of type I IFN-regulated genes in islets from wild-type and STING-deficient NOD mice. The number of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)STING deficiency partially attenuated the type I IFN gene signature in islets but did not suppress insulitis. STING-deficient NOD mice accumulated an increased number of IGRPData suggest that sensing of endogenous nucleic acids through the STING pathway may be partially responsible for the type I IFN gene signature but not autoimmunity in NOD mice. Our results show that the STING pathway may play an unexpected intrinsic role in suppressing the number of diabetogenic T cells. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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