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Function of cGAS-STING pathway. cGAS senses cytosolic DNA from viruses as well as damaged DNA or micronuclei from CIN. Binding of cGAS to cytosolic DNA produces cGAMP, a molecule that interacts with STING to activate the type I interferon pathway. STING activates the expression of NF-κB and phosphorylates IRF3 to induce the production of IL6 and IFNβ, cytokines that mediate inflammation, vasculopathy, and fibrosis.
Source publication
Fibrosis in systemic sclerosis (SSc or scleroderma) is characterized by an abundance of chromosome segregation defects and chromosome instability (CIN) that lead to overactivation of autoimmunity and inflammation. This chapter will emphasize the most recent findings on the involvement of centromere and telomere dysfunction in scleroderma. We will d...
Contexts in source publication
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... is an enzyme that senses cytosolic double-stranded DNA from pathogens or damaged self-DNA, such as micronuclei, as part of the innate immune response (Figure 4) [50][51][52][53]. Upon binding to cytosolic DNA, cGAS produces cGAMP, which interacts with STING to trigger downstream activation of the type I interferon pathway [52,53]. ...
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... recruits TBK1 to phosphorylate the transcription factor IRF3, which translocates to the nucleus and induce production of type I interferons including IFNβ [53]. Activation of STING also triggers RELA (p65), a component of the NFKB that induces IFNβ and pro-inflammatory cytokines, such as IL6 (Figure 4) [49]. cGAS-STING pathway activation is impeded by BANF, which competes with cGAS binding to intracellular DNA, and TREX1, which associates with cGAS and degrades the DNA [54][55][56]. ...
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... is possible that telomere attrition leads to an excess of shelterin proteins that leak to the cytoplasm and act as antigens in a subset of SSc patients. Taken together, these studies suggest that telomere dysfunction affects chromosome segregation and may promote inflammation and fibrosis in SSc as indicated in Figure 4. ...
