ArticleProceedings of the National Academy of Sciences of the United States of America2007
CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 456 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
456 citing papers in PubMed, 2 syntheses or guidelines pooled it, 832 citations in OpenAlex.
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- The TLR9 Agonist Cobitolimod Induces IL10-Producing Wound Healing Macrophages and Regulatory T Cells in Ulcerative Colitis.Journal of Crohn's & colitis · 2020Trial
- CXCR2-mediated metabolic interaction between prostate cancer cells and the immunosuppressive tumor microenvironment.Journal for immunotherapy of cancer · 2026Article
- Regulatory T cell attracting therapy accelerates skeletal muscle functional recovery following injury.Scientific reports · 2026Article
- Molecular Mechanisms of Negative Effect of Systemic Lupus Erythematosus on Oogenesis and Meiotic Processes in Oocytes.International journal of molecular sciences · 2026Review
- Modulating Th17/Treg Balance in Alzheimer's Disease: Therapeutic Insights from Natural Compounds and Immunometabolism.Brain sciences · 2026Review
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- DC-CD4 bispecific tolerogenic nanovesicles induce antigen-specific regulatory T cells and ameliorate collagen-induced arthritis in mice.Nature communications · 2026Article
- Advances in the Role of Adipose Tissue in Promoting Injury Repair and Resist Infection.Immunity, inflammation and disease · 2026Review
- Regulatory T Cells in Diabetic Wound Healing: A Comprehensive Review.Journal of inflammation research · 2026Review
- Heart failure and its progression is associated with changed lymphocyte profile in epicardial adipose tissue.Frontiers in immunology · 2026Article
- Neutrophil-to-lymphocyte ratio in amyotrophic lateral sclerosis: a systematic review and meta-analysis.Brain communications · 2026Review
- Sulfated polysaccharide facilitates macrophage-Treg crosstalk to mitigate chronic inflammation in diabetic wound healing.Bioactive materials · 2026Article
- Targeting delayed healing tissues: immune reprogramming of adaptive immune cells by biomaterials.Regenerative biomaterials · 2026Review
- The Effects of In Utero HIV and Antiretroviral Therapy Exposure on Infant T-Cell and Monocyte Activation, Function, and Regulation of Immune-Modulatory Pathways.Mediators of inflammation · 2026Article
- Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells.Cell & bioscience · 2025Review
- T cell-macrophage crosstalk in GVHD and cancer immunotherapy.Cell investigation · 2025Article
- Macrophage-centred crosstalk with infiltrating immune cells in rheumatoid arthritis and its regulation by mesenchymal stem cells.Journal of translational medicine · 2025Review
396 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are potent suppressors of the adaptive immune system, but their effects on innate immune cells are less well known. Here we demonstrate a previously uncharacterized function of Tregs, namely their ability to steer monocyte differentiation toward alternatively activated macrophages (AAM). AAM are cells with strong antiinflammatory potential involved in immune regulation, tissue remodeling, parasite killing, and tumor promotion. We show that, after coculture with Tregs, monocytes/macrophages display typical features of AAM, including up-regulated expression of CD206 (macrophage mannose receptor) and CD163 (hemoglobin scavenger receptor), an increased production of CCL18, and an enhanced phagocytic capacity. In addition, the monocytes/macrophages have reduced expression of HLA-DR and a strongly reduced capacity to respond to LPS in terms of proinflammatory mediator production (IL-1beta, IL-6, IL-8, MIP-1alpha, TNF-alpha), NFkappaB activation, and tyrosine phosphorylation. Mechanistic studies reveal that CD4(+)CD25(+)CD127(low)Foxp3(+) Tregs produce IL-10, IL-4, and IL-13 and that these cytokines are the critical factors involved in the suppression of the proinflammatory cytokine response. In contrast, the Treg-mediated induction of CD206 is entirely cytokine-independent, whereas the up-regulation of CD163, CCL18, and phagocytosis are (partly) dependent on IL-10 but not on IL-4/IL-13. Together these data demonstrate a previously unrecognized function of CD4(+)CD25(+)Foxp3(+) Tregs, namely their ability to induce alternative activation of monocytes/macrophages. Moreover, the data suggest that the Treg-mediated induction of AAM partly involves a novel, cytokine-independent pathway.
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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.