The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Foxp3+CD4+T Cells Improve Healing After Myocardial Infarction by Modulating Monocyte/Macrophage Differentiation
Abstract
Rationale: An exaggerated or persistent inflammatory activation after myocardial infarction (MI) leads to maladaptive healing and subsequent remodeling of the left ventricle. Foxp3+CD4+regulatory T cells (T reg cells) contribute to inflammation resolution. Therefore, T reg cells might influence cardiac healing post-MI. Objective: Our aim was to study the functional role of T reg cells in wound healing post-MI in a mouse model of permanent left coronary artery ligation. Methods and Results: Using a model of genetic T reg-cell ablation (Foxp3 DTR mice), we depleted the T reg-cell compartment before MI induction, resulting in aggravated cardiac inflammation and deteriorated clinical outcome. Mechanistically, T reg-cell depletion was associated with M1-like macrophage polarization, characterized by decreased expression of inflammation-resolving and healing-promoting factors. The phenotype of exacerbated cardiac inflammation and outcome in T reg-cell–ablated mice could be confirmed in a mouse model of anti-CD25 monoclonal antibody–mediated depletion. In contrast, therapeutic T reg-cell activation by superagonistic anti-CD28 monoclonal antibody administration 2 days after MI led to improved healing and survival. Compared with control animals, CD28-SA–treated mice showed increased collagen de novo expression within the scar, correlating with decreased rates of left ventricular ruptures. Therapeutic T reg-cell activation induced an M2-like macrophage differentiation within the healing myocardium, associated with myofibroblast activation and increased expression of monocyte/macrophage-derived proteins fostering wound healing. Conclusions: Our data indicate that T reg cells beneficially influence wound healing after MI by modulating monocyte/macrophage differentiation. Moreover, therapeutic activation of T reg cells constitutes a novel approach to improve healing post-MI.
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Regulatory T Cells and Immune Tolerance
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Dombrowski, Y., O'Hagan, T., Dittmer, M., Penalva, R., Mayoral, S. R., Bankhead, P., Fleville, S., Eleftheriadis, G., Zhao, C., Naughton, M., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4528 · Cited by 533
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Metadata
- Authors
- Weirather, J., Hofmann, U. D. W., Beyersdorf, N., Ramos, G. C., Vogel, B., Frey, A., Ertl, G., Kerkau, T., & Frantz, S.
- Venue
- Circulation Research
- Published
- 2014-06-20
- Volume
- 115
- Issue
- 1
- Pages
- 55-67
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2123270129
- Cited by
- 699
- References
- 59
- FWCI
- 24.85
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Foxp3+CD4+T Cells Improve Healing After Myocardial Infarction by Modulating Monocyte/Macrophage Differentiation. https://app.cochat.ai/papers/10.1161/circresaha.115.303895
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- Weirather, J., Hofmann, U. D. W., Beyersdorf, N., Ramos, G. C., Vogel, B., Frey, A., Ertl, G., Kerkau, T., & Frantz, S. (2014). Foxp3+CD4+T Cells Improve Healing After Myocardial Infarction by Modulating Monocyte/Macrophage Differentiation. Circulation Research. https://doi.org/10.1161/circresaha.115.303895
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