ArticleImmunology and cell biology2016
Human macrophages induce CD4(+)Foxp3(+) regulatory T cells via binding and re-release of TGF-β.
Article in Immunology and cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Debate on the relationship betweenFrontiers in microbiology · 2024Pooled it
- LncRNA AFAP1-AS1 mediates therapy-dependent expression of CCL5, CXCL10 and MMP9 in multiple sclerosis.Biochemistry and biophysics reports · 2026Article
- Mesenchymal stromal cells and neuroinflammation: a multimodal approach to neuroprotection and future therapeutic horizons.Translational neurodegeneration · 2026Review
- ST2 Signaling Regulates Innate Immune Responses in Kidney Injury.bioRxiv : the preprint server for biology · 2026Article
- Regulatory T cells in cardiac allograft vasculopathy: from mechanistic insights to clinical tolerance.Frontiers in immunology · 2026Review
- Identification of an anti-inflammatory action of exosome release in P2YFrontiers in pharmacology · 2025Article
- Tumor-resident microbiota contributes to colorectal cancer liver metastasis by lactylation and immune modulation.Oncogene · 2024Article
- The immunomodulatory effect of oral NaHCOJournal of neuroinflammation · 2024Article
- Exosomes derived from programmed cell death: mechanism and biological significance.Cell communication and signaling : CCS · 2024Review
- The role of immune cells in different stages of atherosclerosis.International journal of medical sciences · 2024Review
- Mesenchymal stem cells-macrophages crosstalk and myeloid malignancy.Frontiers in immunology · 2024Review
- Solid organ transplantation and gut microbiota: a review of the potential immunomodulatory properties of short-chain fatty acids in graft maintenance.Frontiers in cellular and infection microbiology · 2024Review
- Regulatory T cells and macrophages in atherosclerosis: from mechanisms to clinical significance.Frontiers in immunology · 2024Review
- Regulatory macrophages in solid organ xenotransplantation.Korean journal of transplantation · 2023Review
- Targeting Myc-driven stress addiction in colorectal cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- The critical role of apoptosis in mesenchymal stromal cell therapeutics and implications in homeostasis and normal tissue repair.Cellular & molecular immunology · 2023Review
- Multiple Shades of Gray-Macrophages in Acute Allograft Rejection.International journal of molecular sciences · 2023Review
- Article
- Innate immune cellular therapeutics in transplantation.Frontiers in transplantation · 2023Article
- Tissue-Protective and Anti-Inflammatory Landmark of PRP-Treated Mesenchymal Stromal Cells Secretome for Osteoarthritis.International journal of molecular sciences · 2022Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While pro-inflammatory immune responses are a requirement to combat microbes, uncontrolled self-directed inflammatory immune responses are the hallmark of autoimmune diseases. Restoration of immunological tolerance involves both suppression of ongoing tissue-destructive immune responses and re-education of the host immune system. Both functionally immunosuppressive macrophages (M2) and regulatory T cells (Tregs) are implicated in these processes. Their mutual interaction is synergistic in this context and adoptive transfer of each cell type has been functioning as immunotherapy in experimental models, being particularly effective when using M2 macrophages generated with an optimized interleukin-4 (IL-4)/interleukin-10 (IL-10)/transforming growth factor-β (TGF-β) combination. As a prerequisite for eventual translation of M2 therapy into clinical settings we herein studied the induction, stability and mechanism of generation of human induced Tregs (iTregs) by M2 macrophages generated with IL-4/IL-10/TGF-β. The supernatants of monocyte-derived human M2 macrophages robustly induced FOXP3 and other Treg signature molecules such as CTLA-4 and IKZF4 in human naïve CD4 T cells. M2-induced iTregs displayed enhanced FOXP3 stability and low expression of pro-inflammatory cytokines interferon-γ and IL-17, as well as functional immunosuppressive activity compared with control T cells. The FOXP3-inducing activity was dependent on TGF-β, which was both expressed and captured with re-release by M2 macrophages into the soluble supernatant fraction, in which the TGF-β was not confined to extracellular vesicles such as exosomes. We propose that adoptive transfer of human M2 macrophages may be exploited in the future to induce Tregs in situ by delivering TGF-β, which could be developed as a therapeutic strategy to target autoimmune and other inflammatory diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.