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Cited by 23interferon and immune responsesImmune Response and InflammationCancer Immunotherapy and Biomarkers

Dynamic STING repression orchestrates immune cell development and function

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Knox, Kennady, Jeltema, Devon, Dobbs, Nicole, Yang, Kun, Xing, Cong, Song, Kun, Tang, Zhen, Torres-Ramirez, Gustavo +6 more·2025·Science Immunology
DOI 10.1126/sciimmunol.ado9933PMC PMC13383849
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Abstract

STING is an essential component of the innate immune system, yet homeostatic STING expression patterns and regulation are unknown. Using Sting1 IRES-EGFP reporter and conditional Sting1 transgenic mice, we found that regulation of STING expression is critical for immune cell development and functionality. STING expression was repressed in neutrophils, and forced STING expression or signaling drove systemic inflammatory disease. During T lymphocyte development, STING expression was restricted at the double-positive stage via epigenetic silencing by DNA methyltransferase 1. Forced STING expression or signaling impaired T lymphocyte development independent of type I interferon and promoted lineage commitment to innate-like γδ T cells over adaptive αβ T cells. In the tumor microenvironment, CD8 + T lymphocytes repressed STING expression, correlating with features of T cell exhaustion in syngeneic mouse tumors and human colorectal cancer. Our data demonstrate the necessity of controlled, rather than ubiquitous, STING expression, uncovering a previously unappreciated dimension of STING pathobiology.

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  • The cGAS-STING pathway recognizes mitochondrial DNA released during liver injury, leading to its activation and triggering inflammation with production of type I interferons and proinflammatory cytokines, which exacerbates liver inflammation and hepatocyte damage.

    “It can recognize mtDNA released during liver injury, leading to its activation and the triggering of inflammation with the production of type I interferons (IFNs) and proinflammatory cytokines, which exacerbates liver inflammation and hepatocyte damage (20–22).”

    From Matrix mechanical remodeled carrier-free nanosystem for programmable closed-loop reversal of liver fibrosis via STING alkylation (2025) · cites this paper as [22]

    Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

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References 73 · Cited by 23

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Authors
Knox, K., Jeltema, D., Dobbs, N., Yang, K., Xing, C., Song, K., Tang, Z., Torres-Ramirez, G., Wang, J., Gao, S., Wu, T., Yao, C., Wang, J., & Yan, N.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • Tianjin Medical University Cancer Institute and Hospital (CN)
  • Harold C. Simmons Comprehensive Cancer Center (US)
Corresponding author
  • Wang, Jian
  • Yan, Nan
ORCID
Venue
Science Immunology
Publisher
American Association for the Advancement of Science (AAAS)
Published
2025-03-07
Volume
10
Issue
105
Pages
eado9933-eado9933
ISSN
2470-9468 (ISSN-L)
DOI
10.1126/sciimmunol.ado9933
PMC
PMC13383849
OpenAlex
W4408236158
Cited by
23
References
73
Citations by year
2026: 15 · 2025: 8
FWCI
8.52
Type
journal article
Language
en
Open access
Locations
  • Science Immunology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Cancer Prevention and Research Institute of Texas (RP220242)
  • University of Pennsylvania
  • University of Texas Southwestern Medical Center (CA142543, P30CA142543, SCR_017949)
  • National Natural Science Foundation of China (82373279)
  • National Institutes of Health (SCR_017949, 5t32ai005284-45, CA142543, AI151708, 5T32AI005284)
  • National Cancer Institute ((CA142543), SCR_017949, P30CA142543)
  • National Institute of Allergy and Infectious Diseases (T32-AI005284, R56AI151708, R01AI151708, R56AI134877)
  • National Institute of Neurological Disorders and Stroke (R01NS117424, R01NS122825)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
STING, innate immunity, neutrophils, T cell development, epigenetic silencing, DNMT1, γδ T cells, alpha beta T cells, systemic inflammation, CD8+ T cell exhaustion, tumor microenvironment, colorectal cancer, conditional transgenic mice
MeSH terms
STING Protein, Animals, Humans, Immunity, Innate, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Neutrophils, Colorectal Neoplasms, CD8-Positive T-Lymphocytes, Mice, Tumor Microenvironment

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