ArticleProceedings of the National Academy of Sciences of the United States of America2014
Marginal zone CD169+ macrophages coordinate apoptotic cell-driven cellular recruitment and tolerance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
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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.
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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
71 citing papers in PubMed, 108 citations in OpenAlex.
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- Tumor-Induced Splenic Remodeling: Mechanisms of Systemic Immunosuppression and Emerging Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- CD169Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Review
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- Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights.Stem cell research & therapy · 2025Review
- Immunosuppressive cells in acute myeloid leukemia: mechanisms and therapeutic target.Frontiers in immunology · 2025Review
- Chemokines in the resolution of inflammation: key players and targets for therapeutic modulation.Frontiers in immunology · 2025Review
- Roles of macrophages in lupus nephritis.Frontiers in pharmacology · 2024Review
- Crosstalk between efferocytic myeloid cells and T-cells and its relevance to atherosclerosis.Frontiers in immunology · 2024Review
- Immune regulation through tryptophan metabolism.Experimental & molecular medicine · 2023Review
- Integration of whole transcriptome spatial profiling with protein markers.Nature biotechnology · 2023Article
- Influence of the irradiated pulmonary microenvironment on macrophage and T cell dynamics.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2023Article
- Exploring the Impact of Cyanidin-3-Glucoside on Inflammatory Bowel Diseases: Investigating New Mechanisms for Emerging Interventions.International journal of molecular sciences · 2023Review
- CD169Cancers · 2023Article
- Caspase-9 driven murine model of selective cell apoptosis and efferocytosis.Cell death & disease · 2023Article
- Role of IDO expression in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy.BMC cancer · 2022Article
- Myeloid checkpoints for cancer immunotherapy.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2022Article
- Blood monocyte-derived CD169Nature communications · 2022Article
- Immodulin peptides influence musculoskeletal homeostasis by linking extracellular cues to macrophage and myoblast nuclear receptors.European journal of translational myology · 2022Article
11 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
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Tolerance to apoptotic cells is essential to prevent inflammatory pathology. Though innate responses are critical for immune suppression, our understanding of early innate immunity driven by apoptosis is lacking. Herein we report apoptotic cells induce expression of the chemokine CCL22 in splenic metallophillic macrophages, which is critical for tolerance. Systemic challenge with apoptotic cells induced rapid production of CCL22 in CD169(+) (metallophillic) macrophages, resulting in accumulation and activation of FoxP3(+) Tregs and CD11c(+) dendritic cells, an effect that could be inhibited by antagonizing CCL22-driven chemotaxis. This mechanism was essential for suppression after apoptotic cell challenge, because neutralizing CCL22 or its receptor, reducing Treg numbers, or blocking effector mechanisms abrogated splenic TGF-β and IL-10 induction; this promoted a shift to proinflammatory cytokines associated with a failure to suppress T cells. Similarly, CCR4 inhibition blocked long-term, apoptotic cell-induced tolerance to allografts. Finally, CCR4 inhibition resulted in a systemic breakdown of tolerance to self after apoptotic cell injection with rapid increases in anti-dsDNA IgG and immune complex deposition. Thus, the data demonstrate CCL22-dependent chemotaxis is a key early innate response required for apoptotic cell-induced suppression, implicating a previously unknown mechanism of macrophage-dependent coordination of early events leading to stable tolerance.
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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.