Foxp3+ CD4+ T cells improve healing after myocardial infarction by modulating monocyte/macrophage differentiation - PubMed (original) (raw)
Foxp3+ CD4+ T cells improve healing after myocardial infarction by modulating monocyte/macrophage differentiation
Johannes Weirather et al. Circ Res. 2014.
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 (Treg cells) contribute to inflammation resolution. Therefore, Treg cells might influence cardiac healing post-MI.
Objective: Our aim was to study the functional role of Treg cells in wound healing post-MI in a mouse model of permanent left coronary artery ligation.
Methods and results: Using a model of genetic Treg-cell ablation (Foxp3(DTR) mice), we depleted the Treg-cell compartment before MI induction, resulting in aggravated cardiac inflammation and deteriorated clinical outcome. Mechanistically, Treg-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 Treg-cell-ablated mice could be confirmed in a mouse model of anti-CD25 monoclonal antibody-mediated depletion. In contrast, therapeutic Treg-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 Treg-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 Treg cells beneficially influence wound healing after MI by modulating monocyte/macrophage differentiation. Moreover, therapeutic activation of Treg cells constitutes a novel approach to improve healing post-MI.
Keywords: myocardial infarction; wound healing.
© 2014 American Heart Association, Inc.
Comment in
- Regulating repair: regulatory T cells in myocardial infarction.
Nahrendorf M, Swirski FK. Nahrendorf M, et al. Circ Res. 2014 Jun 20;115(1):7-9. doi: 10.1161/CIRCRESAHA.114.304295. Circ Res. 2014. PMID: 24951758 Free PMC article. No abstract available.
Similar articles
- Regulatory T cells ameliorate cardiac remodeling after myocardial infarction.
Tang TT, Yuan J, Zhu ZF, Zhang WC, Xiao H, Xia N, Yan XX, Nie SF, Liu J, Zhou SF, Li JJ, Yao R, Liao MY, Tu X, Liao YH, Cheng X. Tang TT, et al. Basic Res Cardiol. 2012 Jan;107(1):232. doi: 10.1007/s00395-011-0232-6. Epub 2011 Dec 22. Basic Res Cardiol. 2012. PMID: 22189560 - Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells.
Zeng Z, Yu K, Chen L, Li W, Xiao H, Huang Z. Zeng Z, et al. J Immunol Res. 2016;2016:8493767. doi: 10.1155/2016/8493767. Epub 2016 Apr 6. J Immunol Res. 2016. PMID: 27144181 Free PMC article. - Activation of CD4+ T lymphocytes improves wound healing and survival after experimental myocardial infarction in mice.
Hofmann U, Beyersdorf N, Weirather J, Podolskaya A, Bauersachs J, Ertl G, Kerkau T, Frantz S. Hofmann U, et al. Circulation. 2012 Apr 3;125(13):1652-63. doi: 10.1161/CIRCULATIONAHA.111.044164. Epub 2012 Mar 2. Circulation. 2012. PMID: 22388323 - Role of lymphocytes in myocardial injury, healing, and remodeling after myocardial infarction.
Hofmann U, Frantz S. Hofmann U, et al. Circ Res. 2015 Jan 16;116(2):354-67. doi: 10.1161/CIRCRESAHA.116.304072. Circ Res. 2015. PMID: 25593279 Review. - Regulatory T lymphocytes in myocardial infarction: A promising new therapeutic target.
Wang YP, Xie Y, Ma H, Su SA, Wang YD, Wang JA, Xiang MX. Wang YP, et al. Int J Cardiol. 2016 Jan 15;203:923-8. doi: 10.1016/j.ijcard.2015.11.078. Epub 2015 Nov 10. Int J Cardiol. 2016. PMID: 26618254 Review.
Cited by
- A potential coagulation-related diagnostic model associated with immune infiltration for acute myocardial infarction.
Liu G, Liao W, Lv X, Huang L, He M, Li L. Liu G, et al. Genes Immun. 2024 Oct 8. doi: 10.1038/s41435-024-00298-z. Online ahead of print. Genes Immun. 2024. PMID: 39379556 - IL-4-Induced Gene 1: A Potential Player in Myocardial Infarction.
Shen R, Ding Y, Dong Q, Wang Y, Yu J, Pan C, Cai Y, Li Z, Zhang J, Yu K, Zeng Q. Shen R, et al. Rev Cardiovasc Med. 2024 Sep 20;25(9):337. doi: 10.31083/j.rcm2509337. eCollection 2024 Sep. Rev Cardiovasc Med. 2024. PMID: 39355609 Free PMC article. Review. - The Role of Inflammation in the Pathogenesis of Cardiogenic Shock Secondary to Acute Myocardial Infarction: A Narrative Review.
Kologrivova I, Kercheva M, Panteleev O, Ryabov V. Kologrivova I, et al. Biomedicines. 2024 Sep 11;12(9):2073. doi: 10.3390/biomedicines12092073. Biomedicines. 2024. PMID: 39335587 Free PMC article. Review. - Local administration of regulatory T cells promotes tissue healing.
Nayer B, Tan JL, Alshoubaki YK, Lu YZ, Legrand JMD, Lau S, Hu N, Park AJ, Wang XN, Amann-Zalcenstein D, Hickey PF, Wilson T, Kuhn GA, Müller R, Vasanthakumar A, Akira S, Martino MM. Nayer B, et al. Nat Commun. 2024 Sep 9;15(1):7863. doi: 10.1038/s41467-024-51353-2. Nat Commun. 2024. PMID: 39251592 Free PMC article. - Reward system activation improves recovery from acute myocardial infarction.
Haykin H, Avishai E, Krot M, Ghiringhelli M, Reshef M, Abboud Y, Melamed S, Merom S, Boshnak N, Azulay-Debby H, Ziv T, Gepstein L, Rolls A. Haykin H, et al. Nat Cardiovasc Res. 2024 Jul;3(7):841-856. doi: 10.1038/s44161-024-00491-3. Epub 2024 Jul 12. Nat Cardiovasc Res. 2024. PMID: 39196183
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials