Background and aims Type I interferon is one of the most critical cytokines involving in lupus pathogenesis. The activation of endosomal nucleic acid sensors leading to type I IFN production empowers the lupus phenotypes in several mouse models. The signalling of cytosolic DNA sensor also induces type I IFN production and the role in lupus disease are not clear. Stimulator of interferon genes (Sting), also known as transmembrane protein 173 (TMEM173) and MPYS/MITA/ERIS, is a cytosolic DNA sensor which recognised cyclic di-GMP and subsequently stimulated type I interferon production. The Fcgr2b-deficient mice develop spontaneous lupus phenotypes which are splenomegaly, the presence of anti-nuclear antibodies (ANA) and fatal glomerulonephritis. The polymorphisms of FCGR2B associates with the increases of lupus susceptibility in human. The goal of the study is to identify the role of Sting in lupus mouse model.
Methods The Sting-deficient mice were bred with the Fcgr2b-deficient mice to create double deficient mice and control littermates. The mice were analysed for survival rate, autoantibodies production, severity of pathology, gene expression profiles, and immunophenotypes.
Results In the absence of Sting, the Fcgr2b-deficient mice survived longer and the level of ANA and anti-dsDNA antibody considerably reduced. The glomerulonephritis in the double-deficient mice also ameliorated. The expression of interferon inducible genes such as Cxcl10, Mx1, and Irf5 in the kidneys of the double-deficient mice was significantly lower than the Fcgr2b-deficient mice.
Conclusions Sting-mediated signalling pathway plays the substantial role in lupus pathogenesis of the Fcgr2b-deficient mice. Blocking Sting function may be the advantage for treatment in lupus patients.
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