ArticleThe Journal of allergy and clinical immunology2016
Nonreceptor tyrosine kinases ITK and BTK negatively regulate mast cell proinflammatory responses to lipopolysaccharide.
Article in The Journal of allergy and clinical immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- The role of gut microbiota in neuropathic pain: insights into immune mechanisms.The journal of headache and pain · 2025Review
- Ibrutinib inhibits the replication of multiple poxviruses by targeting the Bruton tyrosine kinase.Journal of virology · 2025Article
- Role of microbiota in pain: From bench to bedside.iMetaOmics · 2025Review
- TREM2 aggravates sepsis by inhibiting fatty acid oxidation via the SHP1/BTK axis.The Journal of clinical investigation · 2024Article
- Exploring the biomarkers and potential therapeutic drugs for sepsis via integrated bioinformatic analysis.BMC infectious diseases · 2024Article
- Article
- Regulation of the Tec family of non-receptor tyrosine kinases in cardiovascular disease.Cell death discovery · 2022Review
- Identification of Immune-Related Key Genes as Potential Diagnostic Biomarkers of Sepsis in Children.Journal of inflammation research · 2022Article
- Analysis of Sepsis Markers and Pathogenesis Based on Gene Differential Expression and Protein Interaction Network.Journal of healthcare engineering · 2022Article
- BTK Promotes Atherosclerosis by Regulating Oxidative Stress, Mitochondrial Injury, and ER Stress of Macrophages.Oxidative medicine and cellular longevity · 2021Article
- Screening of Key Genes of Sepsis and Septic Shock Using Bioinformatics Analysis.Journal of inflammation research · 2021Article
- Review
- Screening of key genes related to the prognosis of mouse sepsis.Bioscience reports · 2020Article
- Systems-Based Interactome Analysis for Hematopoiesis Effect of Angelicae sinensis Radix: Regulated Network of Cell Proliferation towards Hemopoiesis.Chinese journal of integrative medicine · 2019Article
- Interleukin-2-Inducible T-Cell Kinase Deficiency Impairs Early Pulmonary Protection AgainstFrontiers in immunology · 2019Article
- Mast Cells Are Mediators of Fibrosis and Effector Cell Recruitment in Dermal Chronic Graft-vs.-Host Disease.Frontiers in immunology · 2019Article
- Changes of Foxo3a in PBMCs and its associations with stress hyperglycemia in acute obstructive suppurative cholangitis patients.Oncotarget · 2017Article
- ITK signalling via the Ras/IRF4 pathway regulates the development and function of Tr1 cells.Nature communications · 2017Article
- Role(s) of IL-2 inducible T cell kinase and Bruton's tyrosine kinase in mast cell response to lipopolysaccharide.Genomics data · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMast cells are indispensable for LPS-induced septic hypothermia, in which TNF-α plays an essential role to initiate septic responses. ITK and BTK regulate mast cell responses to allergens, but their roles in mast cell responses in LPS-induced sepsis are unclear.
objectiveWe sought to investigate the roles of ITK and BTK in mast cell responses during LPS-induced septic inflammation.
methodsMice (genetically modified or bone marrow-derived mast cell-reconstituted Sash) were given LPS to induce septic hypothermia in the presence or absence of indicated inhibitors. Flow cytometry was used to determine LPS-induced cell influx and TNF-α production in peritoneal cells. Microarray was used for genomewide gene expression analysis on bone marrow-derived mast cells. Quantitative PCR and multiplex were used to determine transcribed and secreted proinflammatory cytokines. Microscopy and Western blotting were used to determine activation of signal transduction pathways.
resultsThe absence of ITK and BTK leads to exacerbation of LPS-induced septic hypothermia and neutrophil influx. Itk(-/-)Btk(-/-) mast cells exhibit hyperactive preformed and LPS-induced TNF-α production, and lead to more severe LPS-induced septic hypothermia when reconstituted into mast cell-deficient Sash mice. LPS-induced nuclear factor kappa B, Akt, and p38 activation is enhanced in Itk(-/-)Btk(-/-) mast cells, and blockage of phosphatidylinositol-4,5-bisphosphate 3-kinase, Akt, or p38 downstream mitogen-activated protein kinase interacting serine/threonine kinase 1 activation significantly suppresses TNF-α hyperproduction and attenuates septic hypothermia.
conclusionsITK and BTK regulate thermal homeostasis during septic response through mast cell function in mice. They share regulatory function downstream of Toll-like receptor 4/LPS in mast cells, through regulating the activation of canonical nuclear factor kappa B, phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt, and p38 signaling pathways.
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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.