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Regulatory T Cells Promote Macrophage Efferocytosis during Inflammation Resolution
Open accessAbstract
Regulatory T (Treg) cell responses and apoptotic cell clearance (efferocytosis) represent critical arms of the inflammation resolution response. We sought to determine whether these processes might be linked through Treg-cell-mediated enhancement of efferocytosis. In zymosan-induced peritonitis and lipopolysaccharide-induced lung injury, Treg cells increased early in resolution, and Treg cell depletion decreased efferocytosis. In advanced atherosclerosis, where defective efferocytosis drives disease progression, Treg cell expansion improved efferocytosis. Mechanistic studies revealed the following sequence: (1) Treg cells secreted interleukin-13 (IL-13), which stimulated IL-10 production in macrophages; (2) autocrine-paracrine signaling by IL-10 induced Vav1 in macrophages; and (3) Vav1 activated Rac1 to promote apoptotic cell engulfment. In summary, Treg cells promote macrophage efferocytosis during inflammation resolution via a transcellular signaling pathway that enhances apoptotic cell internalization. These findings suggest an expanded role of Treg cells in inflammation resolution and provide a mechanistic basis for Treg-cell-enhancement strategies for non-resolving inflammatory diseases.
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In the citing paper
“They contribute to the control and termination of the inflammatory response by producing anti‐inflammatory cytokines such as IL‐10, TGF‐β, and IL‐35.[ 9 ]”
From Ccl2-Induced Regulatory T Cells Balance Inflammation Through Macrophage Polarization During Liver Reconstitution (2024) · cites this paper as [9]
Experimental — accuracy not yet measuredIn the citing paper
“and new work indicates that a cellular pathway of the inflammation resolution response — mediated by regulatory T cells — also promotes efferocytosis79.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [79]
In the citing paper
“The mechanism of the regulatory T cell response involves secretion of IL-13, which in turn stimulates macrophages to secrete and then be activated by the pro-efferocytic cytokine IL-10 (REF79).”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [79]
In the citing paper
“The impaired ability of macrophage efferocytosis would enhance atherogenesis [139,140,141] and atherosclerotic plaque instability [142,143,144].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [139]
In the citing paper
“The elevated IL-10 signaling upregulates macrophage STAT3-mediated VAV1 (a guanine nucleotide exchange factor), which activates GTPase Rac1 to enhance apoptotic cell engulfment by macrophages [139].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [139]
In the citing paper
“activated Treg cells secrete IL-13 to stimulate IL-10 production in macrophages via binding to the IL-13 receptor.”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [139]
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Metadata
- Authors
- Proto, J. D., Doran, A. C., Gusarova, G., Yurdagul, A., Sozen, E., Subramanian, M., Islam, M. N., Rymond, C. C., Du, J., Hook, J., Kuriakose, G., Bhattacharya, J., & Tabas, I.
- Affiliations
- Columbia University (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Tabas, Ira
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 49
- Issue
- 4
- Pages
- 666-677.e6
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC6192849
- OpenAlex
- W2894606588
- Cited by
- 441
- References
- 49
- Citations by year
- 2026: 49 · 2025: 68 · 2024: 68 · 2023: 73 · 2022: 72 · 2021: 47 · 2020: 33 · 2019: 29 · 2018: 2
- FWCI
- 11.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Dspace Repository (Marmara Üniversitesi) (submittedVersion, other-oa)
- Funders
- NIH (HL007343, HL122730, DoD-PR150672, HL132412, HL075662, HL127464, 5P30DK063608, P30CA013696)
- American Heart Association
- Scientific and Technological Research Council of Turkey
- BIDEB 2214/A Program
- Stony Wold-Herbert Fund Inc.
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- regulatory T cells, macrophage efferocytosis, efferocytosis, inflammation resolution, IL-13, IL-10, Vav1, Rac1, zymosan-induced peritonitis, lipopolysaccharide-induced lung injury, atherosclerosis, Treg depletion
- MeSH terms
- Animals, Cell Line, Cells, Cultured, Humans, Inflammation, Lipopolysaccharides, Lung Diseases, Macrophages, Mice, Inbred C57BL, Peritonitis, Phagocytosis, Zymosan, Interleukin-10, Apoptosis, Mice, Knockout, Interleukin-13, Jurkat Cells, T-Lymphocytes, Regulatory
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