2021
DOI: 10.3389/fimmu.2021.605930
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Abstract: Detection of DNA is an important determinant of host-defense but also a driver of autoinflammatory and autoimmune diseases. Failure to degrade self-DNA in DNAseII or III(TREX1)-deficient mice results in activation of the cGAS-STING pathway. Deficiency of cGAS or STING in these models ameliorates disease manifestations. However, the contribution of the cGAS-STING pathway, relative to endosomal TLRs, in systemic lupus erythematosus (SLE) is controversial. In fact, STING deficiency failed to rescue, and actually … Show more

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Cited by 19 publications
(80 citation statements)
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References 56 publications
(80 reference statements)
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“…Our findings are overall in line with a recent study reporting that the cGAS-STING pathway does not promote autoimmunity in two murine models of SLE, the pristane induced lupus model and the genetically programmed MRL/lpr model ( 49 ). Whereas that study investigated the role of global cGAS or STING knock-out, thus affecting myeloid, lymphoid and stromal cells alike, the present study interrogated the role of the cGAS-STING pathway in GC B cells specifically.…”
Section: Discussionsupporting
confidence: 92%
“…Our findings are overall in line with a recent study reporting that the cGAS-STING pathway does not promote autoimmunity in two murine models of SLE, the pristane induced lupus model and the genetically programmed MRL/lpr model ( 49 ). Whereas that study investigated the role of global cGAS or STING knock-out, thus affecting myeloid, lymphoid and stromal cells alike, the present study interrogated the role of the cGAS-STING pathway in GC B cells specifically.…”
Section: Discussionsupporting
confidence: 92%
“…Recent work has suggested that STING simultaneously stimulates the production of pro-and anti-inflammatory cytokines to facilitate the maintenance of gut homeostasis (Ahn et al, 2017), and studies in mouse models of systemic lupus erythematosus (SLE) have indicated STING signaling can be pro-or anti-inflammatory depending on the model (Sharma et al, 2015;Thim-uam et al, 2020;Motwani et al, 2021). Still, the autoimmune syndrome SAVI, caused by gain-offunction mutations in STING, results in excessive inflammation, indicating a primarily pro-inflammatory role for STING (Liu et al, 2014).…”
Section: Discussionmentioning
confidence: 99%
“…We determined that loss of cGAS or STING resulted in a broadly blunted immune response 24hrs after injury. Recent work has suggested that STING simultaneously stimulates the production of pro-and anti-inflammatory cytokines to facilitate maintenance of gut homeostasis [55], and studies in mouse models of systemic lupus erythematosus (SLE) have indicated STING signaling can be pro-or antiinflammatory depending on the model [56][57][58]. Still, the autoimmune syndrome SAVI that results from gain-of-function mutations in STING results in excessive inflammation, indicating a primarily pro-inflammatory role for STING [59].…”
Section: Discussionmentioning
confidence: 99%