ArticleJournal of immunology (Baltimore, Md. : 1950)2021
STING Agonist Mitigates Experimental Autoimmune Encephalomyelitis by Stimulating Type I IFN-Dependent and -Independent Immune-Regulatory Pathways.
Article in Journal of immunology (Baltimore, Md. : 1950), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Spatiotemporal control of STING activation and saRNA delivery decouples humoral and cellular immunity.bioRxiv : the preprint server for biology · 2026Article
- The cGAS-STING Pathway: A Double-Edged Regulator of Neuroinflammation and Myelin Regeneration.Molecular neurobiology · 2026Review
- cGAS-STING axis: A central regulator of neural homeostasis and neuroinflammatory pathogenesis.Neural regeneration research · 2026Article
- The cGAS-STING Pathway Drives Astrocyte-Mediated Demyelination in Multiple Sclerosis Through Clusterin Secretion.CNS neuroscience & therapeutics · 2026Article
- STING agonist protects against exacerbation of schistosome egg-induced immunopathology.PLoS pathogens · 2026Article
- Nanotechnology-driven STING regulation for on-demand therapy.Acta pharmaceutica Sinica. B · 2026Review
- STING/type I interferon pathway is required for antigen-containing PLGA nanoparticle- and apoptotic cell-induced CD4+ T cell tolerance.Science advances · 2026Article
- STING Signaling Deficiency Exacerbates Demyelination and Immune Infiltration in Focal EAE Lesions.NeuroSci · 2025Article
- Targeting Impaired Type I Interferon-IL-27 Signaling Rescues T Regulatory Cell Suppressive Function in Relapsing-Remitting Multiple Sclerosis.bioRxiv : the preprint server for biology · 2025Article
- Comparative molecular, innate, and adaptive impacts of chemically diverse STING agonists.Vaccine · 2025Review
- Targeting microglia-Th17 feed-forward loop to suppress autoimmune neuroinflammation.Journal of neuroinflammation · 2025Article
- An injectable subcutaneous colon-specific immune niche for the treatment of ulcerative colitis.Nature biomedical engineering · 2024Article
- Polymeric cGAMP microparticles affect the immunogenicity of a broadly active influenza mRNA lipid nanoparticle vaccine.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Cytosolic DNA sensors in neurodegenerative diseases: from physiological defenders to pathological culprits.EMBO molecular medicine · 2024Review
- Monocyte regulation by gut microbial signals.Trends in microbiology · 2023Review
- Multiple Sclerosis: Inflammatory and Neuroglial Aspects.Current issues in molecular biology · 2023Review
- Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases.Zoological research · 2023Review
- JMJD3 regulates diabetic wound repair in a STINGy fashion.Cellular & molecular immunology · 2023Article
- Development of a broadly active influenza intranasal vaccine adjuvanted with self-assembled particles composed of mastoparan-7 and CpG.Frontiers in immunology · 2023Article
- Intracellular Sensing of DNA in Autoinflammation and Autoimmunity.Arthritis & rheumatology (Hoboken, N.J.) · 2022Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
The cGAS-cyclic GMP-AMP (cGAMP)-stimulator of IFN genes (STING) pathway induces a powerful type I IFN (IFN-I) response and is a prime candidate for augmenting immunity in cancer immunotherapy and vaccines. IFN-I also has immune-regulatory functions manifested in several autoimmune diseases and is a first-line therapy for relapsing-remitting multiple sclerosis. However, it is only moderately effective and can induce adverse effects and neutralizing Abs in recipients. Targeting cGAMP in autoimmunity is unexplored and represents a challenge because of the intracellular location of its receptor, STING. We used microparticle (MP)-encapsulated cGAMP to increase cellular delivery, achieve dose sparing, and reduce potential toxicity. In the C57BL/6 experimental allergic encephalomyelitis (EAE) model, cGAMP encapsulated in MPs (cGAMP MPs) administered therapeutically protected mice from EAE in a STING-dependent fashion, whereas soluble cGAMP was ineffective. Protection was also observed in a relapsing-remitting model. Importantly, cGAMP MPs protected against EAE at the peak of disease and were more effective than rIFN-β. Mechanistically, cGAMP MPs showed both IFN-I-dependent and -independent immunosuppressive effects. Furthermore, it induced the immunosuppressive cytokine IL-27 without requiring IFN-I. This augmented IL-10 expression through activated ERK and CREB. IL-27 and subsequent IL-10 were the most important cytokines to mitigate autoreactivity. Critically, cGAMP MPs promoted IFN-I as well as the immunoregulatory cytokines IL-27 and IL-10 in PBMCs from relapsing-remitting multiple sclerosis patients. Collectively, this study reveals a previously unappreciated immune-regulatory effect of cGAMP that can be harnessed to restrain T cell autoreactivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.