STING-Dependent Signaling Manifests IL-10 Controlled Inflammatory Colitis
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ABSTRACT:
PROVIDER: PRJNA421445 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-02-01 | GSE107811 | GEO
Project description:Intestinal immune homeostasis is preserved by commensal bacteria interacting with the host to generate a balanced array of cytokines that are essential for wound repair and for combatting infection. Inflammatory bowel disease (IBD), which can lead to colitis-associated cancer (CAC), is thought to involve chronic microbial irritation following a breach of the mucosal intestinal epithelium. However, the innate immune pathways responsible for regulating these inflammatory processes remain to be fully clarified. Here, we show that commensal bacteria influence STING signaling predominantly in mononuclear phagocytes to produce both pro-inflammatory cytokines as well as anti-inflammatory IL-10. Enterocolitis, manifested through loss of IL-10, was completely abrogated in the absence of STING. Intestinal inflammation was less severe in the absence of cGAS, possibly suggesting a role for cyclic dinucleotides (CDNs) indirectly regulating STING signaling. Our data shed insight into the causes of inflammation and provide a potential therapeutic target for prevention of IBD.
| S-EPMC6082386 | biostudies-literature
Project description:Ulcerative colitis (UC) develops through a complicated interaction between the host and microbiota. Intestinal fibroblasts are suggested to play crucial roles in the pathogenesis of UC. However, the influences of the host-microbiota interaction on the pathophysiology of intestinal fibroblasts remain poorly understood. Here, we reveal that OTUD3 suppresses pathologic activation of fibroblasts exposed to microbial cyclic GMP-AMP (3’3’-cGAMP) by deubiquitinating stimulator of interferon genes (STING) in the colon. Sting deficiency ameliorated dextran sodium sulfate-induced colitis in Otud3-/- mice. In addition, mice harboring an UC risk missense variant in the Otud3 gene showed pathological features of UC in the colon after transplantation of a fecal microbiome with the potential to produce excessive cGAMP from UC patients. Collectively, these results demonstrate the critical role of OTUD3 in the maintenance of intestinal homeostasis and highlight one mechanism of the interaction between the host (OTUD3 in fibroblasts) and microbiota (STING agonist) in UC development.
2025-05-12 | GSE244076 | GEO
Project description:Ulcerative colitis (UC) develops through a complicated interaction between the host and microbiota. Intestinal fibroblasts are suggested to play crucial roles in the pathogenesis of UC. However, the influences of the host-microbiota interaction on the pathophysiology of intestinal fibroblasts remain poorly understood. Here, we reveal that OTUD3 suppresses pathologic activation of fibroblasts exposed to microbial cyclic GMP-AMP (3’3’-cGAMP) by deubiquitinating stimulator of interferon genes (STING) in the colon. Sting deficiency ameliorated dextran sodium sulfate-induced colitis in Otud3-/- mice. In addition, mice harboring an UC risk missense variant in the Otud3 gene showed pathological features of UC in the colon after transplantation of a fecal microbiome with the potential to produce excessive cGAMP from UC patients. Collectively, these results demonstrate the critical role of OTUD3 in the maintenance of intestinal homeostasis and highlight one mechanism of the interaction between the host (OTUD3 in fibroblasts) and microbiota (STING agonist) in UC development.
2025-05-12 | GSE244078 | GEO
Project description:Ulcerative colitis (UC) develops through a complicated interaction between the host and microbiota. Intestinal fibroblasts are suggested to play crucial roles in the pathogenesis of UC. However, the influences of the host-microbiota interaction on the pathophysiology of intestinal fibroblasts remain poorly understood. Here, we reveal that OTUD3 suppresses pathologic activation of fibroblasts exposed to microbial cyclic GMP-AMP (3’3’-cGAMP) by deubiquitinating stimulator of interferon genes (STING) in the colon. Sting deficiency ameliorated dextran sodium sulfate-induced colitis in Otud3-/- mice. In addition, mice harboring an UC risk missense variant in the Otud3 gene showed pathological features of UC in the colon after transplantation of a fecal microbiome with the potential to produce excessive cGAMP from UC patients. Collectively, these results demonstrate the critical role of OTUD3 in the maintenance of intestinal homeostasis and highlight one mechanism of the interaction between the host (OTUD3 in fibroblasts) and microbiota (STING agonist) in UC development.
2025-05-12 | GSE244077 | GEO
Project description:Ulcerative colitis (UC) develops through a complicated interaction between the host and microbiota. Intestinal fibroblasts are suggested to play crucial roles in the pathogenesis of UC. However, the influences of the host-microbiota interaction on the pathophysiology of intestinal fibroblasts remain poorly understood. Here, we reveal that OTUD3 suppresses pathologic activation of fibroblasts exposed to microbial cyclic GMP-AMP (3’3’-cGAMP) by deubiquitinating stimulator of interferon genes (STING) in the colon. Sting deficiency ameliorated dextran sodium sulfate-induced colitis in Otud3-/- mice. In addition, mice harboring an UC risk missense variant in the Otud3 gene showed pathological features of UC in the colon after transplantation of a fecal microbiome with the potential to produce excessive cGAMP from UC patients. Collectively, these results demonstrate the critical role of OTUD3 in the maintenance of intestinal homeostasis and highlight one mechanism of the interaction between the host (OTUD3 in fibroblasts) and microbiota (STING agonist) in UC development.
2025-05-12 | GSE244080 | GEO
Project description:Ulcerative colitis (UC) develops through a complicated interaction between the host and microbiota. Intestinal fibroblasts are suggested to play crucial roles in the pathogenesis of UC. However, the influences of the host-microbiota interaction on the pathophysiology of intestinal fibroblasts remain poorly understood. Here, we reveal that OTUD3 suppresses pathologic activation of fibroblasts exposed to microbial cyclic GMP-AMP (3’3’-cGAMP) by deubiquitinating stimulator of interferon genes (STING) in the colon. Sting deficiency ameliorated dextran sodium sulfate-induced colitis in Otud3-/- mice. In addition, mice harboring an UC risk missense variant in the Otud3 gene showed pathological features of UC in the colon after transplantation of a fecal microbiome with the potential to produce excessive cGAMP from UC patients. Collectively, these results demonstrate the critical role of OTUD3 in the maintenance of intestinal homeostasis and highlight one mechanism of the interaction between the host (OTUD3 in fibroblasts) and microbiota (STING agonist) in UC development.
2025-05-12 | GSE244079 | GEO
Project description:<p>With the rising incidence of IBD and limitations of current therapies, novel strategies are urgently needed. Recent studies have highlighted natural products in colitis treatment. Here, we investigated the therapeutic effects and mechanisms of lily polysaccharides (LP) in DSS-induced ulcerative colitis (UC). LP supplementation, alone or combined with N8-acetylspermidine (N8AS), alleviated weight loss and intestinal inflammation, restored microbial homeostasis, and increased beneficial bacteria like Bacteroidetes. LP significantly elevated N8AS levels, and exogenous N8AS also ameliorated UC symptoms. Mechanistically, LP and N8AS inhibited the cGAS–STING signaling pathway, reduced pro-inflammatory cytokine production, and promoted intestinal barrier repair in vitro. These results suggest that LP exerts anti-colitic effects via modulation of the microbiota/N8AS/cGAS–STING axis. This study identifies LP as a promising natural therapeutic for UC by linking microbiota regulation, metabolic modulation, and immune signaling inhibition.</p>
2025-09-29 | MTBLS13064 | MetaboLights
Project description:The goal of the experiment was to compare the liver transcriptional profile of wild-type and IL-10 knockout mice with colitis. Colitis was induced in 6 week old female wild-type and IL-10-deficient C57BL/6 mice by administration of 3% dextran sulfate sodium (DSS) in the drinking water for 7 days. At necropsy, segments of liver were homogenized in Trizol and total RNA prepared for the transcriptional profiling. Total RNA from 4 wild-type and 4 IL-10 knockout mice with colitis was used to hybridize to Affymetrix Gene Chip Mouse 2.0 ST arrays.
2014-05-01 | E-GEOD-52168 | biostudies-arrayexpress
Project description:OTUD3 prevents ulcerative colitis by modulating microbiota-mediated STING activation.
| PRJNA1021199 | ENA