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25 Stimulator of interferon genes (sting) plays a crucial role in type-i ifn production induced by the sera from sle patients
  1. Y Kato,
  2. A Kumanogoh,
  3. H Takamatsu and
  4. J Park
  1. Osaka University, Dept. of Respiratory Medicine- Allergy and Rheumatic Disesase- Graduate School of medicne, Suita- Osaka, Japan

Abstract

Background and Aims Type-I interferon (IFN-I) plays important roles in the pathogenesis of SLE. It has been reported that serum IFN-I levels are high in active SLE patients and that IFN-I is produced when DNA sensors recognise DNA-containing immune complex. Stimulator of interferon genes (STING) is known as a key molecule in cytosolic DNA-sensing, which leads to IFN-I production. However, the involvement of STING in the pathogenesis of SLE has not been clarified. We studied the role of STING in the production of IFN-I in SLE.

Methods We evaluated both the IFN-I bioactivity in sera and the serum-mediated type-I IFN-inducing activity (IFN-I-IA) in SLE by using two different reporter cell lines. Also, to address contribution of STING in the production of IFN-I, we established the STING-deficient reporter cell lines (STING-KO) using the CRISPR/Cas9 system.

Results IFN-I bioactivity was high in the sera from SLE compared with other autoimmune diseases and healthy controls. Serum-induced IFN-I-IA was also higher in SLE than those in other autoimmune diseases. These reporter cell lines do not respond to the ligands of Toll like receptor (TLR) 8 or TLR9, suggesting the existence of TLR8/9-independent IFN-I-inducing mechanism. Consistently, the enhanced IFN-I-IA in SLE was reduced in the STING-KO, indicating that STING is involved in the serum-induced IFN-I production.

Conclusions Our finding suggests that IFN-I bioactivity is high in the sera of SLE, and that these sera have a potential to induce IFN-I production through STING.

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