title: Positive feedback regulation of type I interferon by the interferon-stimulated gene STING.
abstract: Stimulator of interferon genes (STING) is an important regulator of the innate immune response to cytoplasmic DNA. However, regulation of STING itself is largely unknown. Here, we show that STING transcription is induced by innate immune activators, such as cyclic dinucleotides (CDNs), through an IFNAR1- and STAT1-dependent pathway. We also identify a STAT1 binding site in the STING promoter that contributes to the activation of STING transcription. Furthermore, we show that induction of STING mediates the positive feedback regulation of CDN-triggered IFN-I. Thus, our study demonstrates that STING is an interferon-stimulated gene (ISG) and its induction is crucial for the IFN-I positive feedback loop.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Division of Oral Biology and Medicine, School of Dentistry and Broad Stem Cell Research Center, University of California, Los Angeles, CA, USA.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA.
authors.forename: Shankar S
authors.initials: SS
authors.lastname: Iyer
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA gcheng@mednet.ucla.edu.
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D007113:Immunity, Innate / Q000235:genetics; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D007372:Interferons / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000099197:STING Protein
chemical_list: D007370:Interferon Type I; D007372:Interferons; D008565:Membrane Proteins; D053633:Receptor, Interferon alpha-beta; D050794:STAT1 Transcription Factor; C532857:STING1 protein, human; D000099197:STING Protein; C530855:Sting1 protein, mouse
keywords: CDN; IFN; ISG; STING; cGAMP