ArticleThe Journal of experimental medicine2025
PARP7 inhibits type I interferon signaling to prevent autoimmunity and lung disease.
Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- PARP7 inhibition and a STING agonist potentiate radiation-induced immunogenicity in glioblastoma.Oncoimmunology · 2026Article
- PARP7 inhibitors enhance the immunogenic effects of radiation in pancreatic cancer cells.Molecular therapy. Oncology · 2026Article
- PARP inhibitor YCH1899 activates type I interferon signaling and synergizes with STING agonists in BRCA-proficient tumors.Molecular biomedicine · 2026Article
- Macrophage PARP7 Alleviates Septic Cardiomyopathy by Interacting With TBK1 and Suppressing TBK1-Driven Inflammatory Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Aryl hydrocarbon receptor pharmacology-mechanisms, ligands, and therapeutic potential.Pharmacological reviews · 2026Review
- PARP7 alleviates lipopolysaccharide-induced acute kidney injury by inhibiting TBK1-driven inflammation in renal tubular epithelial cells.Molecular medicine (Cambridge, Mass.) · 2026Article
- PARP7 protects the lung epithelial barrier from diverse environmental threats.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- NADCell reports · 2026Article
- The CNS Meninges and the Synovial Joint: Parallel Immunological Structures in Autoimmune Disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Obesity-induced metabolic reprogramming of the tumor immune microenvironment: mechanisms, spatial niches, and immunotherapy response.Frontiers in immunology · 2026Review
- Roles of ADP-Ribosyltransferases in Cancer.Oncology research · 2026Review
- PARP7 and aryl hydrocarbon receptor differentially regulate mammary cancer cell proliferation and STING-induced type I interferon signalling.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- PARP7 Suppresses Radiation-induced Necroptosis and Abscopal Immunity.Research square · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Type I IFN (IFN-I) induce hundreds of antiviral genes as well as negative regulators that limit IFN-I signaling. Here, we investigate the family of 16 PARPs and find that 11 PARPs are ISGs, of which 8 PARPs inhibit IFN-I production. PARP7 is the most potent negative feedback regulator of IFN-I production. Using Parp7-/- and Parp7H532A/H532A mice, we show that PARP7 loss leads to systemic autoimmunity characterized by splenomegaly and increased autoantibodies and inflammatory cytokines. PARP7 loss also results in perivascular immune infiltration in the lung that forms tertiary lymphoid structures. Mechanistically, PARP7 inhibits multiple innate immune pathways in a cell-intrinsic and MARylation-dependent manner. PARP7 interacts with IRF3 through the catalytic domain and disrupts the IRF3:CBP/p300 transcriptional holocomplex required for IFN-I production. Irf3-/- or Irf3S1/S1 (transcription defective) or Sting-/- rescues Parp7H532A/H532A mouse autoimmunity and lung disease. Together, our study reveals physiological functions of PARP7 as a negative feedback regulator of IFN-I production that maintains immune homeostasis particularly in the lung.
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Registered trials
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