ArticleJCI insight2024
Tregs from human blood differentiate into nonlymphoid tissue-resident effector cells upon TNFR2 costimulation.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 9 citations in OpenAlex.
- Ligand-Blocking and Agonist Antibodies Targeting TNFR2 Use Distinct Modes of Action to Induce Antitumor Immunity.Cancer research · 2026Article
- Tissue-resident memory T cells in organ transplantation: implications for immune homeostasis and graft outcomes.Inflammation and regeneration · 2026Review
- TRIP13 promotes the expansion and immunosuppression of CD4Cell death & disease · 2026Article
- Antibody targeting of the TNF-TNFR2 axis to overcome tumor immune resistance.Frontiers in immunology · 2026Review
- Defining nature, responses and drivers of regulatory- and conventional CD4Frontiers in immunology · 2026Article
- Regulatory T cells in cardiac allograft vasculopathy: from mechanistic insights to clinical tolerance.Frontiers in immunology · 2026Review
- Decoding Treg diversity and dysfunction to advance Treg-based therapies in autoimmune and inflammatory diseases.Frontiers in immunology · 2026Review
- Treg Susceptibility to Cladribine-Induced Depletion Correlates With Therapy Response in Patients With Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- TNF Production or TNFR2 Expression Characterize Distinct States of Regulatory T Cells that Cooperate in Treg Expansion in Cancer and Chronic Inflammation.European journal of immunology · 2025Article
- Pharmacotherapeutic strategies to promote regulatory T cell function in autoimmunity.Current opinion in immunology · 2025Review
- Interferon-γ-stimulated antigen-presenting cancer-associated fibroblasts hinder neoadjuvant chemoimmunotherapy efficacy in lung cancer.Cell reports. Medicine · 2025Article
- Anti-PD-1 amplifies costimulation in melanoma-infiltrating TJournal for immunotherapy of cancer · 2025Article
- Transcriptional fingerprinting of regulatory T cells: ensuring quality in cell therapy applications.Frontiers in immunology · 2025Article
- A novel TNFR2 agonist peptide for the expansion of CD4+Foxp3+ regulatory T cells.Frontiers in immunology · 2025Article
- The immunobiology and therapeutic potential of regulatory T cells in autoimmune diseases and allergic diseases.Frontiers in immunology · 2025Review
- Tissue-specific roles of regulatory T cells: mechanisms of suppression and beyond along with emerging therapeutic insights in autoimmune indications.Frontiers in immunology · 2025Review
- Tissue determinants of the human T cell receptor repertoire.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tregs can facilitate transplant tolerance and attenuate autoimmune and inflammatory diseases. Therefore, it is clinically relevant to stimulate Treg expansion and function in vivo and to create therapeutic Treg products in vitro. We report that TNF receptor 2 (TNFR2) is a unique costimulus for naive, thymus-derived Tregs (tTregs) from human blood that promotes their differentiation into nonlymphoid tissue-resident (NLT-resident) effector Tregs, without Th-like polarization. In contrast, CD28 costimulation maintains a lymphoid tissue-resident (LT-resident) Treg phenotype. We base this conclusion on transcriptome and proteome analysis of TNFR2- and CD28-costimulated CD4+ tTregs and conventional T cells (Tconvs), followed by bioinformatic comparison with published transcriptomic Treg signatures from NLT and LT in health and disease, including autoimmunity and cancer. These analyses illuminate that TNFR2 costimulation promoted tTreg capacity for survival, migration, immunosuppression, and tissue regeneration. Functional studies confirmed improved migratory ability of TNFR2-costimulated tTregs. Flow cytometry validated the presence of the TNFR2-driven tTreg signature in effector/memory Tregs from the human placenta, as opposed to blood. Thus, TNFR2 can be exploited as a driver of NLT-resident tTreg differentiation for adoptive cell therapy or antibody-based immunomodulation in human disease.
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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.