ArticleJournal of immunology (Baltimore, Md. : 1950)2013
The role of JAK-3 in regulating TLR-mediated inflammatory cytokine production in innate immune cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 76 citations in OpenAlex.
- Intestinal epithelial cell-specific deletion of Jak2 disrupts gut homeostasis.Scientific reports · 2026Article
- Bovine endometrial organoids: a new tool to study conceptus-maternal interactions in mammals†.Biology of reproduction · 2026Article
- A novel small molecule KMU-11361 attenuates rheumatoid arthritis by mechanistic inhibition of the TAK1-NF-κB-NLRP3 axis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Paradoxical Activation of Entheseal Myeloid Cells by JAK1 and Tyk2 Inhibitors via Interleukin-10 Antagonism.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Electret-Inspired Charge-Injected Hydrogel for Scar-Free Healing of Bacterially Infected Burns Through Bioelectrical Stimulation and Immune Modulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tandem kinase proteins across the plant kingdom.Nature genetics · 2025Article
- Evaluating the role of astragalus polysaccharide in modulating immune infiltration and enhancing prognostic biomarkers in pediatric acute myeloid leukemia.Frontiers in pharmacology · 2025Article
- Temporal evolution and inter-patient heterogeneity in primary and recurrent head and neck squamous cell carcinoma.BJC reports · 2024Article
- Integrated-omics analysis with explainable deep networks on pathobiology of infant bronchiolitis.NPJ systems biology and applications · 2024Article
- Mechanistic target of rapamycin in regulating macrophage function in inflammatory cardiovascular diseases.Journal of molecular and cellular cardiology · 2024Review
- JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions.Molecular biomedicine · 2023Review
- Selective Inhibitors of Janus Kinase 3 Modify Responses to Lipopolysaccharides by Increasing the Interleukin-10-to-Tumor Necrosis Factor α Ratio.ACS pharmacology & translational science · 2023Article
- Influence of Advanced Organ Support (ADVOS) on Cytokine Levels in Patients with Acute-on-Chronic Liver Failure (ACLF).Journal of clinical medicine · 2022Article
- Transcriptional Alterations in Dorsolateral Prefrontal Cortex and Nucleus Accumbens Implicate Neuroinflammation and Synaptic Remodeling in Opioid Use Disorder.Biological psychiatry · 2021Article
- Oclacitinib, a Janus Kinase Inhibitor, Reduces the Frequency of IL-4- and IL-10-, but Not IFN-γ-, Producing Murine CD4Molecules (Basel, Switzerland) · 2021Article
- A comparative analysis of the intrauterine transcriptome in fertile and subfertile mares using cytobrush sampling.BMC genomics · 2021Article
- CUL4B negatively regulates Toll-like receptor-triggered proinflammatory responses by repressing Pten transcription.Cellular & molecular immunology · 2021Article
- Disease Risk-Associated Genetic Variants inJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Transcriptomics uncovers substantial variability associated with alterations in manufacturing processes of macrophage cell therapy products.Scientific reports · 2020Article
- Differential regulation of JAK/STAT-signaling in patients with ulcerative colitis and Crohn's disease.World journal of gastroenterology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The role of JAK-3 in TLR-mediated innate immune responses is poorly understood, although the suppressive function of JAK3 inhibition in adaptive immune response has been well studied. In this study, we found that JAK3 inhibition enhanced TLR-mediated immune responses by differentially regulating pro- and anti- inflammatory cytokine production in innate immune cells. Specifically, JAK3 inhibition by pharmacological inhibitors or specific small interfering RNA or JAK3 gene knockout resulted in an increase in TLR-mediated production of proinflammatory cytokines while concurrently decreasing the production of IL-10. Inhibition of JAK3 suppressed phosphorylation of PI3K downstream effectors including Akt, mammalian target of rapamycin complex 1, glycogen synthase kinase 3β (GSK3β), and CREB. Constitutive activation of Akt or inhibition of GSK3β abrogated the capability of JAK3 inhibition to enhance proinflammatory cytokines and suppress IL-10 production. In contrast, inhibition of PI3K enhanced this regulatory ability of JAK3 in LPS-stimulated monocytes. At the transcriptional level, JAK3 knockout lead to the increased phosphorylation of STATs that could be attenuated by neutralization of de novo inflammatory cytokines. JAK3 inhibition exhibited a GSK3 activity-dependent ability to enhance phosphorylation levels and DNA binding of NF-κB p65. Moreover, JAK3 inhibition correlated with an increased CD4(+) T cell response. Additionally, higher neutrophil infiltration, IL-17 expression, and intestinal epithelium erosion were observed in JAK3 knockout mice. These findings demonstrate the negative regulatory function of JAK3 and elucidate the signaling pathway by which JAK3 differentially regulates TLR-mediated inflammatory cytokine production in innate immune cells.
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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.