ArticleStem cell research & therapy2020
TNFα/TNFR2 signaling pathway: an active immune checkpoint for mesenchymal stem cell immunoregulatory function.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Elevation of circulating TNF receptor 2 in cancer: A systematic meta-analysis for its potential as a diagnostic cancer biomarker.Frontiers in immunology · 2022Pooled it
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- Extracellular vesicles and their cargo molecules for peripheral nerve injuries and neuropathies: The composition, properties, and impact.Molecular aspects of medicine · 2026Review
- Proinflammatory Cytokine Preconditioning Enhances the Therapeutic Potency of Different Types of MSCs in Inflammation.International journal of molecular sciences · 2026Article
- Multi-Omics Analysis Reveals the Potential Preventive Mechanism of Lactobacillus salivarius Li01 Against L-Arginine-Induced Acute Pancreatitis in Mice.Microbial biotechnology · 2026Article
- Upfront whole blood transcriptional patterns in patients receiving immune checkpoint inhibitors associate with clinical outcome.Cancer immunology, immunotherapy : CII · 2025Article
- Mesenchymal stromal cells conditioned by peripheral blood mononuclear cells exert enhanced immunomodulation capacities and alleviate a model of Myasthenia Gravis.Stem cell research & therapy · 2025Article
- The Role of TNF-α in Neuropathic Pain: An Immunotherapeutic Perspective.Life (Basel, Switzerland) · 2025Review
- Role of Tumor Necrosis Factor in Tuberculosis.Biomolecules · 2025Review
- CD163, a novel receptor for TNF, was revealedHeliyon · 2025Article
- In situ blockade of TNF-TNFR2 axis via oncolytic adenovirus improves antitumor efficacy in solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The effects of prenatal administration of tumor necrosis factor-α on osteocalcin and RANK expression in newborn mice.Journal of molecular histology · 2025Article
- Understanding the role of TNFR2 signaling in the tumor microenvironment of breast cancer.Journal of experimental & clinical cancer research : CR · 2024Review
- Therapeutic effect of three-dimensional hanging drop cultured human umbilical cord mesenchymal stem cells on osteoarthritis in rabbits.Stem cell research & therapy · 2024Article
- Targeting TNFR2 for cancer immunotherapy: recent advances and future directions.Journal of translational medicine · 2024Review
- Therapeutic and immunomodulatory potentials of mesenchymal stromal/stem cells and immune checkpoints related molecules.Biomarker research · 2024Review
- Engineering mesenchymal stem cells for premature ovarian failure: overcoming challenges and innovating therapeutic strategies.Theranostics · 2024Review
- Generic design principles for antibody-based tumour necrosis factor (TNF) receptor 2 (TNFR2) agonists with FcγR-independent agonism.Theranostics · 2024Article
- TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond.Nature reviews. Rheumatology · 2023Review
- Effects of Modified Glucosamine on the Chondrogenic Potential of Circulating Stem Cells under Experimental Inflammation.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn addition to their multilineage potential, mesenchymal stem cells (MSCs) have a broad range of functions from tissue regeneration to immunomodulation. MSCs have the ability to modulate the immune response and change the progression of different inflammatory and autoimmune disorders. However, there are still many challenges to overcome before their widespread clinical administration including the mechanisms behind their immunoregulatory function. MSCs inhibit effector T cells and other immune cells, while inducing regulatory T cells (T regs), thus, reducing directly and indirectly the production of pro-inflammatory cytokines. TNF/TNFR signaling plays a dual role: while the interaction of TNFα with TNFR1 mediates pro-inflammatory effects and cell death, its interaction with TNFR2 mediates anti-inflammatory effects and cell survival. Many immunosuppressive cells like T regs, regulatory B cells (B regs), endothelial progenitor cells (EPCs), and myeloid-derived suppressor cells (MDSCs) express TNFR2, and this is directly related to their immunosuppression efficiency. In this article, we investigated the role of the TNFα/TNFR2 immune checkpoint signaling pathway in the immunomodulatory capacities of MSCs.
methodsCo-cultures of MSCs from wild-type (WT) and TNFR2 knocked-out (TNFR2 KO) mice with T cells (WT and TNFα KO) were performed under various experimental conditions.
resultsWe demonstrate that TNFR2 is a key regulatory molecule which is strongly involved in the immunomodulatory properties of MSCs. This includes their ability to suppress T cell proliferation, activation, and pro-inflammatory cytokine production, in addition to their capacity to induce active T regs.
conclusionsOur results reveal for the first time the importance of the TNFα/TNFR2 axis as an active immune checkpoint regulating MSC immunological functions.
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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.