title: The regional function of cGAS/STING signal in multiple organs: One of culprit behind systemic lupus erythematosus?
abstract: The systemic dysregulation of adaptive and innate immunity have been identified as major hallmark of systemic lupus erythematosus (SLE) pathogenesis that predominantly affects women. Patients with SLE develop heterogeneous clinical manifestations which involve of multiple organ damage including renal, spleen, nervous system, joints and hematopoietic organs. A high rate of cell death, e.g., NETosis, and clearance deficiencies by myeloid cells led to increased cell debris and accumulation of endogenous nucleic acids, and the presence of anti-nuclear antibodies (ANAs) derived from immune response can break of self-tolerance and exacerbate SLE pathology. Currently, the nucleic acid receptors, such as Toll-like receptors, RIG-I-like receptors, AIM2-like receptors and IFI 200-family have been uncovered to be potential predisposing causes for SLE via triggering interferon (IFN) response and maturation of IL-1β. Notably, as the newly found DNA sensor, cyclic GMP-AMP synthase (cGAS) can activate the stimulator of interferon genes (STING), which plays a pivotal role in DNA/RNA sensing pathway, for type I IFN and other inflammatory cytokines induction including IL-6 and attributes to STING-associated inflammatory disorders. Interestingly, the elevated levels of IFN-α/β and IFN-stimulated genes were found in SLE patients than healthy individuals. Given this, we propose a hypothesis that the cGAS-STING pathway in multiple organs function versatile and can facilitate overall disease progression of SLE though impertinent cytosolic self-DNA sensing.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology and Hospital of Stomatology, Medical School, Nanjing University, Nanjing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ding
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology and Hospital of Stomatology, Medical School, Nanjing University, Nanjing, China.
authors.forename: Guanjun
authors.initials: G
authors.lastname: Dong
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology and Hospital of Stomatology, Medical School, Nanjing University, Nanjing, China.
authors.forename: Dongya
authors.initials: D
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology and Hospital of Stomatology, Medical School, Nanjing University, Nanjing, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Ni
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology and Hospital of Stomatology, Medical School, Nanjing University, Nanjing, China. Electronic address: yayihou@nju.edu.cn.
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000032:analysis; D018450:Disease Progression; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation; D007370:Interferon Type I / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009713:Nucleotidyltransferases / Q000378:metabolism*; D015398:Signal Transduction; D000099197:STING Protein; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D000974:Antibodies, Antinuclear; D016207:Cytokines; D004247:DNA; D058847:Inflammasomes; D007370:Interferon Type I; D008565:Membrane Proteins; D009713:Nucleotidyltransferases; C532857:STING1 protein, human; D000099197:STING Protein; C530855:Sting1 protein, mouse; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase; C578391:cGAS protein, mouse