ArticleNature communications2024
Dichotomous outcomes of TNFR1 and TNFR2 signaling in NK cell-mediated immune responses during inflammation.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- TNF-α deficiency underlies NK cell dysfunction in colorectal cancer.Oncoimmunology · 2026Article
- TNFα-driven epigenetic upregulation of TIGIT creates a targetable vulnerability in tumors.Oncogene · 2026Article
- Entosis remodels the immune microenvironment of osteosarcoma by regulating macrophage polarization: An integrated study based on multi-omics data and in vitro experiments.Translational oncology · 2026Article
- Modulation of Mu-Opioid Receptor Expression and Functional Impairment of Natural Killer Cells in Neuropathic Pain: Implications for Biomarker Discovery and Personalized Therapies.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Transcriptional Profile Change of NK-92 Cells in Presence of Cytokines, TGFβ Signaling Pathway Inhibitor and CDK7/12/13 Kinase Inhibitor.International journal of molecular sciences · 2026Article
- TNF inhibits SARS-CoV-2 induced cell-cell fusion through activating the SDC4-RhoA signaling to promote actin bundles formation.Cell insight · 2026Article
- Single-Cell Profiling Reveals Distinct Immune Communication Networks in Centenarians and Elderly Controls.Aging cell · 2026Article
- Review
- Upregulation of TNFR2 Precedes TOX Expression by Exhausted T cells and Restricts Antitumor and Antiviral Immunity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Analysis of the diagnostic accuracy of plasma sTNFr-2 concentrations in identifying sarcopenia in community-dwelling older women.Scientific reports · 2025Article
- Enhancing natural killer cell anti-tumour activity through macrophage manipulation.Frontiers in immunology · 2025Review
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cell function is regulated by a balance of activating and inhibitory signals. Tumor necrosis factor (TNF) is an inflammatory cytokine ubiquitous across homeostasis and disease, yet its role in regulation of NK cells remains unclear. Here, we find upregulation of the immune checkpoint protein, T cell immunoglobulin and mucin domain 3 (Tim3), is a biomarker of TNF signaling in NK cells during Salmonella Typhimurium infection. In mice with conditional deficiency of either TNF receptor 1 (TNFR1) or TNF receptor 2 (TNFR2) in NK cells, we find TNFR1 limits bacterial clearance whereas TNFR2 promotes it. Mechanistically, via single cell RNA sequencing we find that both TNFR1 and TNFR2 induce the upregulation of Tim3, while TNFR1 accelerates NK cell death but TNFR2 promotes NK cell accumulation and effector function. Our study thus highlights the complex interplay of TNF-based regulation of NK cells by the two TNF receptors during inflammation.
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