Dysbiosis exacerbates colitis by promoting ubiquitination and accumulation of the innate immune adaptor STING in myeloid cells

Shmuel-Galia, Liraz; Humphries, Fiachra; Lei, Xuqiu; Ceglia, Simona; Wilson, Ruth; Jiang, Zhaozhao; Ketelut-Carneiro, Natália; Foley, Sage E.; Pechhold, Susanne; Houghton, JeanMarie; Muneeruddin, Khaja; Shaffer, Scott A.; McCormick, Beth A.; Reboldi, Andrea; Ward, Doyle V.; Marshak‐Rothstein, Ann; Fitzgerald, Katherine A.

doi:10.1016/j.immuni.2021.05.008

Cited by 75 publications

(67 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…STING activation and accumulation predominantly occurred in intestinal myeloid cells including macrophages and monocytes in colitis. The researchers found that the c-di-GMP triggered the ubiquitination and stabilization of STING to induce a significant increase of IFN-γ-producing Th1 cells and reduction of Treg cells, promoting the progression of colitis ( 96 ), which proved that STING could regulate the differentiation of T cells in the SAVI model to affect the process of the disease once again. Similarly, in the DSS-induced experimental colitis model, STING protein levels were significantly increased in M1 phenotype bone marrow-derived macrophages (BMDMs) or the PMA-differentiated human THP-1-derived macrophages, which predicted that M1 polarized macrophages expressed increasing sensitivity to CDNs.…”

Section: Autoimmune and Inflammatory Diseasesmentioning

confidence: 99%

The cGAS-STING Pathway: A Promising Immunotherapy Target

Ou¹,

Zhang²,

Cheng³

et al. 2021

Front. Immunol.

101

View full text Add to dashboard Cite

With the continuous development of immunotherapy, researchers have paid more attention to the specific immune regulatory mechanisms of various immune responses in different diseases. As a novel and vital innate immune signal pathway, the cGAS-STING signal pathway activated by nucleic acid substances, interplays with other immune responses, by which it participates in regulating cancer, autoimmune and inflammatory diseases, microbial and parasitic infectious diseases, and other diseases. With the exception of its role in innate immunity, the growing list of researches demonstrated expanding roles of the cGAS-STING signal pathway in bridging the innate immunity (macrophage polarization) with the adaptive immunity (T lymphocytes differentiation). Macrophages and T lymphocytes are the most representative cells of innate immunity and adaptive immunity, respectively. Their polarization or differentiation are involved in the pathogenesis and progression of various diseases. Here we mainly summarized recent advanced discoveries of how the cGAS-STING signal pathway regulated macrophages polarization and T lymphocytes differentiation in various diseases and vaccine applications, providing a promising direction for the development and clinical application of immunotherapeutic strategies for related diseases.

show abstract

Section: Autoimmune and Inflammatory Diseasesmentioning

confidence: 99%

The cGAS-STING Pathway: A Promising Immunotherapy Target

Ou¹,

Zhang²,

Cheng³

et al. 2021

Front. Immunol.

101

View full text Add to dashboard Cite

show abstract

“…Our discovery that exogenous CDNs impact immunity has parallels in mammalian systems and has broad implications in enteric biology (Aden et al, 2018;Ahn et al, 2017;Shmuel-Galia et al, 2021). First, CDN recognition may be deeply conserved, as it is likely commensals from flies to humans produce CDNs.…”

Section: Discussionmentioning

confidence: 99%

“…Studies suggest that intestinal STING may sense the microbiota (Ahn et al, 2017;Shmuel-Galia et al, 2021). Therefore, we hypothesized enteric dSTING may be activated by CDNs produced by local commensals and thus investigated the role of orally acquired CDNs in enteric antiviral immunity.…”

Section: Cdns Protect Against Virus Infection and Induce Gene Expression In The Gutmentioning

confidence: 99%

See 1 more Smart Citation

Orally acquired cyclic dinucleotides drive dSTING-dependent antiviral immunity in enterocytes

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The extended data of the study further showed that microbiota products such as c-di-GMP contributes to STING stabilization in intestinal myeloid cells. 72 Notably, microbiota DNA could induce the production of type I IFN dependent on STING pathway in wide-type (WT) mice lamina propria cells. 15 However, the involvement of microbiota DNA in the pathogenesis of IBD has not been reported yet.…”

Section: Pathogen-derived Dna and Gi Inflammatory Diseasementioning

confidence: 99%

cGAS–STING signaling pathway in gastrointestinal inflammatory disease and cancers

Jiang

2021

The FASEB Journal

View full text Add to dashboard Cite

Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has emerged as a key DNA-sensing machinery in innate immunity. Activation of cGAS-STING signaling pathway mediates the production of interferons and proinflammatory cytokines. Although cGAS-STING signaling pathway shows critical function in the maintenance of gut homeostasis, overactive cGAS-STING signaling pathway leads to gastrointestinal (GI) inflammation.Harnessing the effect and mechanism of the cGAS-STING signaling pathway could be beneficial for the development of novel strategies for the treatment of GI diseases. This review presents recent advances regarding the role of cGAS-STING signaling pathway in GI inflammatory disease and cancers and describes perspective therapeutic strategies targeting the signaling pathway.

show abstract

Dysbiosis exacerbates colitis by promoting ubiquitination and accumulation of the innate immune adaptor STING in myeloid cells

Cited by 75 publications

References 65 publications

The cGAS-STING Pathway: A Promising Immunotherapy Target

The cGAS-STING Pathway: A Promising Immunotherapy Target

Orally acquired cyclic dinucleotides drive dSTING-dependent antiviral immunity in enterocytes

cGAS–STING signaling pathway in gastrointestinal inflammatory disease and cancers

Contact Info

Product

Resources

About