ArticleThe Journal of clinical investigation2020
Bruton tyrosine kinase deficiency augments NLRP3 inflammasome activation and causes IL-1β-mediated colitis.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 2 of them syntheses that pooled it.
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Who cites it
64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- The impact of post-translational modifications and subcellular localization on NLRP3 inflammasome activation: A systematic review.Cell communication and signaling : CCS · 2025Pooled it
- Crohn's-like Enteritis in X-Linked Agammaglobulinemia: A Case Series and Systematic Review.The journal of allergy and clinical immunology. In practice · 2021Pooled it
- Inhibition of ERK5 activity ameliorates osteoarthritis by suppressing NLRP3 inflammasome-mediated chondrocyte pyroptosis.Bone research · 2026Article
- Interleukin-18 armours antitumour immune effectors.Nature reviews. Immunology · 2026Review
- Cardiotoxicity of Targeted Therapies in Hematologic Malignancies: From Molecular Mechanisms to Clinical Management.Current treatment options in oncology · 2026Review
- Nrf2 promotes NLRP3 inflammasome assembly and activation by Klf9-TXNIP axis.Cell death discovery · 2026Article
- Post-translational modifications of NLRP3: to prime or not to prime?Trends in immunology · 2026Review
- Small Interfering RNA (siRNA) as a Targeted Therapy for Acute Respiratory Distress Syndrome: Evidence from Experimental Models.International journal of molecular sciences · 2026Review
- Stratified assessment of platelets in sepsis: from dynamic counts to functional phenotypes.Frontiers in immunology · 2026Review
- Dietary polysaccharides in the management of inflammatory bowel disease: recent advances.Frontiers in nutrition · 2026Review
- GSK461364 Inhibits NLRP3 Inflammasome by Targeting NEK7 Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Monogenic inflammatory bowel disease: An unfolding enigma.World journal of clinical pediatrics · 2025Review
- Decoding NLRP3 Inflammasome Activation in Alzheimer's Disease: A Focus on Receptor Dynamics.Molecular neurobiology · 2025Review
- Peroxiredoxin 1 promotes intestinal inflammation by activating the NLRP3 inflammasome in macrophages through lysosomal disruption in Crohn's disease.Cell death & disease · 2025Article
- Prunus mume derived extracellular vesicle-like particles alleviate experimental colitis via disrupting NEK7-NLRP3 interaction and inflammasome activation.Journal of nanobiotechnology · 2025Article
- Efficacy and potential mechanisms of jatrorrhizine on MNNG-induced chronic atrophic gastritis in rats based on serological metabolomics and molecular docking.Scientific reports · 2025Article
- Updated insights into the molecular networks for NLRP3 inflammasome activation.Cellular & molecular immunology · 2025Review
- Ameliorative effect of nodakenin in combating TNBS-induced ulcerative colitis by suppressing NFƙB-mediated NLRP3 inflammasome pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Case Report: Hematopoietic stem cell transplantation in an adult patient with X-linked agammaglobulinemia and severe refractory enteropathy.Frontiers in immunology · 2025Article
- Fenebrutinib, a Bruton's tyrosine kinase inhibitor, blocks distinct human microglial signaling pathways.Journal of neuroinflammation · 2024Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Bruton tyrosine kinase (BTK) is present in a wide variety of cells and may thus have important non-B cell functions. Here, we explored the function of this kinase in macrophages with studies of its regulation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome. We found that bone marrow-derived macrophages (BMDMs) from BTK-deficient mice or monocytes from patients with X-linked agammaglobulinemia (XLA) exhibited increased NLRP3 inflammasome activity; this was also the case for BMDMs exposed to low doses of BTK inhibitors such as ibrutinib and for monocytes from patients with chronic lymphocytic leukemia being treated with ibrutinib. In mechanistic studies, we found that BTK bound to NLRP3 during the priming phase of inflammasome activation and, in doing so, inhibited LPS- and nigericin-induced assembly of the NLRP3 inflammasome during the activation phase of inflammasome activation. This inhibitory effect was caused by BTK inhibition of protein phosphatase 2A-mediated (PP2A-mediated) dephosphorylation of Ser5 in the pyrin domain of NLRP3. Finally, we show that BTK-deficient mice were subject to severe experimental colitis and that such colitis was normalized by administration of anti-IL-β or anakinra, an inhibitor of IL-1β signaling. Together, these studies strongly suggest that BTK functions as a physiologic inhibitor of NLRP3 inflammasome activation and explain why patients with XLA are prone to develop Crohn's disease.
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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.