ArticleNature communications2021
Defactinib inhibits PYK2 phosphorylation of IRF5 and reduces intestinal inflammation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- A segregating PTK2B variant in a primary biliary cholangitis (PBC) family induces PBC-like autoimmune features in knock-in mice.Cell & bioscience · 2026Article
- Thlaspi arvense attenuates colitis-associated colorectal tumorigenesis through suppression of neutrophil recruitment via the NOD/NF-κB pathway.Chinese medicine · 2026Article
- Functional sQTLs regulating PTK2B exon 31 splicing uncover an RNA-dependent modulation of its kinase activity and cellular phenotype.Cell communication and signaling : CCS · 2026Article
- Reprogramming Lesional Macrophage Homeostasis via Interferon Regulatory Factor 5 Targeted siRNA Nanoimmunotherapy for Atherosclerosis.ACS nano · 2026Article
- Microwave dynamic therapy induces ferroptosis in colorectal cancer by targeting PTK2B to regulate STAT3-mediated GPX4 expression.Molecular biomedicine · 2025Article
- Interferon Regulator Factor 5: A Novel Inflammatory Marker and Promising Therapeutic Target in Ulcerative Colitis.Biomedicines · 2025Article
- TLR-induced STK25 activation promotes IRF5-mediated inflammation.Life science alliance · 2025Article
- IRF5 Mediates Artery Inflammation in Salt-Sensitive Hypertension by Regulating STAT1 and STAT2 Phosphorylation to Increase ESM1 Transcription: Insights from Bioinformatics and Mechanistic Analysis.International journal of molecular sciences · 2025Article
- Focal Adhesion Kinase Inhibition Ameliorates Burn Injury-Induced Chronic Pain in Rats.Molecular neurobiology · 2025Article
- Research progress of PYK2 in digestive system diseases.Frontiers in immunology · 2025Review
- TRIM21 regulation of IRF-mediated type I interferon signaling in systemic autoimmune diseases.Frontiers in immunology · 2025Review
- The PTK2B gene is associated with obesity, adiposity, and leptin levels in children and adolescents.iScience · 2024Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Enhanced phagocytosis associated with multinucleated microglia via Pyk2 inhibition in an acute β-amyloid infusion model.Journal of neuroinflammation · 2024Article
- Gingerenone A Attenuates Ulcerative Colitis via Targeting IL-17RA to Inhibit Inflammation and Restore Intestinal Barrier Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Lipids regulate peripheral serotonin release via gut CD1d.Immunity · 2023Article
- PF-431396 hydrate inhibition of kinase phosphorylation during adherent-invasiveMicrobiology (Reading, England) · 2023Article
- MiR-222-3p Aggravates the Inflammatory Response by Targeting SOCS1 to Activate STAT3 Signaling in Ulcerative Colitis.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2022Article
- Transcriptome-Wide lncRNA and mRNA Profiling of Spleens from Meishan Pigs at Different Development Stages.Animals : an open access journal from MDPI · 2022Article
- CXCL4 synergizes with TLR8 for TBK1-IRF5 activation, epigenomic remodeling and inflammatory response in human monocytes.Nature communications · 2022Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 4 countries.
Funding
Abstract
Interferon regulating factor 5 (IRF5) is a multifunctional regulator of immune responses, and has a key pathogenic function in gut inflammation, but how IRF5 is modulated is still unclear. Having performed a kinase inhibitor library screening in macrophages, here we identify protein-tyrosine kinase 2-beta (PTK2B/PYK2) as a putative IRF5 kinase. PYK2-deficient macrophages display impaired endogenous IRF5 activation, leading to reduction of inflammatory gene expression. Meanwhile, a PYK2 inhibitor, defactinib, has a similar effect on IRF5 activation in vitro, and induces a transcriptomic signature in macrophages similar to that caused by IRF5 deficiency. Finally, defactinib reduces pro-inflammatory cytokines in human colon biopsies from patients with ulcerative colitis, as well as in a mouse colitis model. Our results thus implicate a function of PYK2 in regulating the inflammatory response in the gut via the IRF5 innate sensing pathway, thereby opening opportunities for related therapeutic interventions for inflammatory bowel diseases and other inflammatory conditions.
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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.