ArticleNature communications2022
Transcription-independent regulation of STING activation and innate immune responses by IRF8 in monocytes.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
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- Enhanced antitumor immunity of mRNA vaccines by bioorthogonal-like delayed activation of exogeneous STING.Nature biotechnology · 2026Article
- Immunomodulatory supramolecular hydrogel for rheumatoid arthritis management via adenosine A2A receptor-mediated macrophage remodeling.Bioactive materials · 2026Article
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- Dissection of innate-immune-ligand- and interferon-protein-mediated transcriptional responses in human THP1 cell states.Communications biology · 2026Article
- Sulfatide deficiency-induced astrogliosis and myelin lipid dyshomeostasis are independent of TREM2-mediated microglial activation.Nature communications · 2026Article
- Mitochondrial retrograde signaling initiates HIF-1α/BNIP3/NIX-mediated mitophagy in Tibetan high-altitude adaptation.Cell death discovery · 2026Article
- PBMC transcriptomic signatures reflect immune dynamics and disease activity in psoriatic arthritis.Frontiers in immunology · 2026Article
- KAT2A affects the inflammatory progression of lupus nephritis through multilevel regulation of cGAS.Journal of molecular medicine (Berlin, Germany) · 2025Article
- cGAS-STING signaling pathway as a therapeutic target in human diseases.Chinese medical journal · 2025Review
- Sensing of Ebinur Lake virus by distinct pattern recognition receptors dictates cell-type specific innate immunity and pathogenesis.Journal of virology · 2025Article
- Single-Cell Transcriptomic Analysis Reveals Cell Heterogeneity and Altered Signaling Pathways in Jellyfish Sting Patients.Marine drugs · 2025Article
- Cyclic GMP-AMP synthase recognizes the physical features of DNA.Acta pharmacologica Sinica · 2025Review
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- Death domain-associated protein (Daxx) impairs colon cancer chemotherapy by inhibiting the cGAS-STING pathway.Oncology research · 2025Article
- The role of interferon regulatory factors in atherosclerosis.Frontiers in cardiovascular medicine · 2025Review
- Interactions between polycyclic aromatic hydrocarbons and genetic variants in the cGAS-STING pathway affect the risk of colorectal cancer.Archives of toxicology · 2024Article
- Mitochondrial DNA copy number and the risk of autoimmune diseases: A Mendelian randomization study with meta-analysis.Journal of translational autoimmunity · 2024Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sensing of cytosolic DNA of microbial or cellular/mitochondrial origin by cGAS initiates innate immune responses via the adaptor protein STING. It remains unresolved how the activity of STING is balanced between a productive innate immune response and induction of autoimmunity. Here we show that interferon regulatory factor 8 (IRF8) is essential for efficient activation of STING-mediated innate immune responses in monocytes. This function of IRF8 is independent of its transcriptional role in monocyte differentiation. In uninfected cells, IRF8 remains inactive via sequestration of its IRF-associated domain by its N- and C-terminal tails, which reduces its association with STING. Upon triggering the DNA sensing pathway, IRF8 is phosphorylated at Serine 151 to allow its association with STING via the IRF-associated domain. This is essential for STING polymerization and TBK1-mediated STING and IRF3 phosphorylation. Consistently, IRF8-deficiency impairs host defense against the DNA virus HSV-1, and blocks DNA damage-induced cellular senescence. Bone marrow-derived mononuclear cells which have an autoimmune phenotype due to deficiency of Trex1, respond to IRF-8 deletion with reduced pro-inflammatory cytokine production. Peripheral blood mononuclear cells from systemic lupus erythematosus patients are characterized by elevated phosphorylation of IRF8 at the same Serine residue we find to be important in STING activation, and in these cells STING is hyper-active. Taken together, the transcription-independent function of IRF8 we describe here appears to mediate STING activation and represents an important regulatory step in the cGAS/STING innate immune pathway in monocytes.
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