ArticleCell death and differentiation2021
TYK2 licenses non-canonical inflammasome activation during endotoxemia.
Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Mendelian randomization and clinical trial evidence supports TYK2 inhibition as a therapeutic target for autoimmune diseases.EBioMedicine · 2023Pooled it
- A single-nucleus multiome analysis of transcriptome and chromatin accessibility reveals cell-type-specific immune modulation for chronic cannabis use among people with HIV infection.bioRxiv : the preprint server for biology · 2026Article
- A smart amphiphilic nanoplatform amplifies ROS-mediated immunogenic cell death to suppress bladder cancer growth and metastasis.Journal of nanobiotechnology · 2025Article
- Regulation of versican expression in macrophages is mediated by canonical type I interferon signaling via ISGF3.American journal of physiology. Cell physiology · 2024Article
- Investigation of missense mutation-related type 1 diabetes mellitus through integrating genomic databases and bioinformatic approach.Genomics & informatics · 2024Article
- Tyrosine kinase 2 modulates splenic B cells through type I IFN and TLR7 signaling.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- Regulation of Versican Expression in Macrophages is Mediated by Canonical Type I Interferon Signaling via ISGF3.bioRxiv : the preprint server for biology · 2024Article
- Pyroptosis in neurodegenerative diseases: from bench to bedside.Cell biology and toxicology · 2023Review
- JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions.Molecular biomedicine · 2023Review
- Defining resistance and tolerance traits in Covid-19: towards a stratified medicine approach.QJM : monthly journal of the Association of Physicians · 2022Article
- How Pyroptosis Contributes to Inflammation and Fibroblast-Macrophage Cross-Talk in Rheumatoid Arthritis.Cells · 2022Review
- MicroRNA-455-3p regulates proliferation and osteoclast differentiation of RAW264.7 cells by targeting PTEN.BMC musculoskeletal disorders · 2022Article
- Pyroptosis-Related Gene Signature Predicts the Prognosis of ccRCC Using TCGA and Single-Cell RNA Seq Database.Journal of healthcare engineering · 2022Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
The non-canonical inflammasome is an emerging crucial player in the development of inflammatory and neurodegenerative diseases. It is activated by direct sensing of cytosolic lipopolysaccharide (LPS) by caspase-11 (CASP11), which then induces pyroptosis, an inflammatory form of regulated cell death. Here, we report that tyrosine kinase 2 (TYK2), a cytokine receptor-associated kinase, is a critical upstream regulator of CASP11. Absence of TYK2 or its kinase activity impairs the transcriptional induction of CASP11 in vitro and in vivo and protects mice from LPS-induced lethality. Lack of TYK2 or its enzymatic activity inhibits macrophage pyroptosis and impairs release of mature IL-1β and IL-18 specifically in response to intracellular LPS. Deletion of TYK2 in myeloid cells reduces LPS-induced IL-1β and IL-18 production in vivo, highlighting the importance of these cells in the inflammatory response to LPS. In support of our data generated with genetically engineered mice, pharmacological inhibition of TYK2 reduced LPS-induced upregulation of CASP11 in bone marrow-derived macrophages (BMDMs) and of its homolog CASP5 in human macrophages. Our study provides insights into the regulation of CASP11 in vivo and uncovered a novel link between TYK2 activity and CASP11-dependent inflammation.
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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.