ArticleCellular signalling2011
Nuclear presence of nuclear factor of activated T cells (NFAT) c3 and c4 is required for Toll-like receptor-activated innate inflammatory response of monocytes/macrophages.
Article in Cellular signalling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 59 citations in OpenAlex.
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- Genome scan for runs of homozygosity in Saanen goats selected under tropical environments reveals candidate genes for adaptive and production traits.Tropical animal health and production · 2025Article
- Unlocking the therapeutic potential of the NFAT pathway in kidney diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Akap5 links synaptic dysfunction to neuroinflammatory signaling in a mouse model of infantile neuronal ceroid lipofuscinosis.Frontiers in synaptic neuroscience · 2024Article
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- Evolutionary mechanisms underlying the diversification of nuclear factor of activated T cells across vertebrates.Scientific reports · 2023Article
- Identification of MicroRNAs RegulatingCurrent issues in molecular biology · 2023Article
- Bioinformatic analysis of gene expression data reveals Src family protein tyrosine kinases as key players in androgenetic alopecia.Frontiers in medicine · 2023Article
- Recent knowledge of NFATc4 in oncogenesis and cancer prognosis.Cancer cell international · 2022Review
- Two birds, one stone: NFATc3 controls dual actions of miR-204 in foam cell formation.European heart journal · 2021Article
- Diabetic Kinome Inhibitors-A New Opportunity for β-Cells Restoration.International journal of molecular sciences · 2021Review
- Hepatic NFAT signaling regulates the expression of inflammatory cytokines in cholestasis.Journal of hepatology · 2021Article
- PolyADP-Ribosylation of NFATc3 and NF-κB Transcription Factors Modulate Macrophage Inflammatory Gene Expression in LPS-Induced Acute Lung Injury.Journal of innate immunity · 2021Article
- Article
- Search for Selection Signatures Related to Trypanosomosis Tolerance in African Goats.Frontiers in genetics · 2021Article
- Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics.Circulation research · 2020Article
- Lipin-1 Contributes to IL-4 Mediated Macrophage Polarization.Frontiers in immunology · 2020Article
- Differential microglia and macrophage profiles in human IDH-mutant and -wild type glioblastoma.Oncotarget · 2019Article
- Calcineurin-NFAT signalling in myeloid leucocytes: new prospects and pitfalls in immunosuppressive therapy.EMBO molecular medicine · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Nuclear factor of activated T cells (NFATs) are crucial transcription factors that tightly control proinflammatory cytokine expression for adaptive immunity in T and B lymphocytes. However, little is known about the role of NFATs for innate immunity in macrophages. In this study, we report that NFAT is required for Toll-like receptor (TLR)-initiated innate immune responses in bone marrow-derived macrophages (BMMs). All TLR ligand stimulation including LPS, a TLR4 ligand, and Pam(3)CSK(4), a TLR1/2 ligand, induced expression of TNF which was inhibited by VIVIT, an NFAT-specific inhibitor peptide. BMMs from NFATc4 knock-out mouse expressed less TNF than wild type. Despite apparent association between NFAT and TNF, LPS did not directly activate NFAT based on NFAT-luciferase reporter assay, whereas NF-κB was inducibly activated by LPS. Instead, macrophage exhibited constitutive NFAT activity which was not increased by LPS and was decreased by VIVIT. Immunocytochemical examination of NFATc1-4 of BMMs exhibited nuclear localization of NFATc3/c4 regardless of LPS stimulation. LPS stimulation did not cause nuclear translocation of NFATc1/c2. Treatment with VIVIT resulted in nuclear export of NFATc3/c4 and inhibited TLR-activated TNF expression, suggesting that nuclear residence of NFATc is required for TLR-related innate immune response. Chromatin immunoprecipitation (ChIP) assay using anti-RNA polymerase II (PolII) antibody suggested that VIVIT decreased PolII binding to TNF gene locus, consistent with VIVIT inhibition of LPS-induced TNF mRNA expression. This study identifies a novel paradigm of innate immune regulation rendered by NFAT which is a well known family of adaptive immune regulatory proteins.
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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.