ArticleThe Journal of clinical investigation2021
TNFR2/14-3-3ε signaling complex instructs macrophage plasticity in inflammation and autoimmunity.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 87 citations in OpenAlex.
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- CCAAT/enhancer binding protein β and its role in autoimmune diseases: a promising therapeutic target.Journal of translational medicine · 2026Review
- Lactylation-related genes contribute to neurological injury and prognosis of acute ischemic stroke based on transcriptome and single-cell sequencing analysis.Cell & bioscience · 2026Article
- The Research Progress of Tumor-Associated Macrophages in Prostate Cancer.Journal of immunology research · 2026Review
- Pneumococcal transmission is driven by TNFR2+ regulatory T-cells.Frontiers in immunology · 2026Article
- Exercise-derived peptide confers protection against septic cardiomyopathy by enhancing CCAAT/enhancer binding protein β-mediated autophagy.Cellular and molecular life sciences : CMLS · 2025Article
- A novel intracellular signaling pathway elicited by DM9CP-6 regulates immune responses in oysters.Cell communication and signaling : CCS · 2025Article
- The CTSZ-TRA2A-IL32 axis defines a targetable macrophage-dependent pathway in metastatic prostate cancer.Journal of translational medicine · 2025Article
- Current cutting-edge omics techniques on musculoskeletal tissues and diseases.Bone research · 2025Review
- SIRT6 Ameliorates Cancer Cachexia-Associated Adipose Wasting by Suppressing TNFR2 Signalling in Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- Progranulin deficiency associates with postmenopausal osteoporosis via increasing ubiquitination of estrogen receptor α.Genes & diseases · 2025Article
- Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.Bone research · 2024Review
- Progranulin: A promising biomarker and therapeutic target for fibrotic diseases.Acta pharmaceutica Sinica. B · 2024Review
- circSORBS1 inhibits lung cancer progression by sponging miR-6779-5p and directly binding RUFY3 mRNA.Journal of translational medicine · 2024Article
- Novel peptide inhibitor of human tumor necrosis factor-α has antiarthritic activity.Scientific reports · 2024Article
- Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances.Cytokine & growth factor reviews · 2024Review
- Comprehensive analysis of the function of helicobacter-associated ferroptosis gene YWHAE in gastric cancer through multi-omics integration, molecular docking, and machine learning.Apoptosis : an international journal on programmed cell death · 2024Article
- Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies.Orthopaedic surgery · 2024Review
- How do small quantities of cartilage sodium channels play a significant role in osteoarthritis?Clinical and translational medicine · 2024Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
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Abstract
TNFR1 and TNFR2 have received prominent attention because of their dominance in the pathogenesis of inflammation and autoimmunity. TNFR1 has been extensively studied and primarily mediates inflammation. TNFR2 remains far less studied, although emerging evidence demonstrates that TNFR2 plays an antiinflammatory and immunoregulatory role in various conditions and diseases. Herein, we report that TNFR2 regulates macrophage polarization, a highly dynamic process controlled by largely unidentified intracellular regulators. Using biochemical copurification and mass spectrometry approaches, we isolated the signaling molecule 14-3-3ε as a component of TNFR2 complexes in response to progranulin stimulation in macrophages. In addition, 14-3-3ε was essential for TNFR2 signaling-mediated regulation of macrophage polarization and switch. Both global and myeloid-specific deletion of 14-3-3ε resulted in exacerbated inflammatory arthritis and counteracted the protective effects of progranulin-mediated TNFR2 activation against inflammation and autoimmunity. TNFR2/14-3-3ε signaled through PI3K/Akt/mTOR to restrict NF-κB activation while simultaneously stimulating C/EBPβ activation, thereby instructing macrophage plasticity. Collectively, this study identifies 14-3-3ε as a previously unrecognized vital component of the TNFR2 receptor complex and provides new insights into the TNFR2 signaling, particularly its role in macrophage polarization with therapeutic implications for various inflammatory and autoimmune diseases with activation of the TNFR2/14-3-3ε antiinflammatory pathway.
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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.