Infarcted Myocardium-Primed Dendritic Cells Improve Remodeling and Cardiac Function After Myocardial Infarction by Modulating the Treg and Macrophage Polarization
Background—Inflammatory responses play a critical role in left ventricular (LV) remodeling after a myocardial infarction (MI). Tolerogenic dendritic cells (tDCs) can modulate immune responses inducing regulatory T cells (Tregs) in a number of inflammatory diseases.
Methods—We generated tDCs by treating bone marrow-derived dendritic cells with TNF-α and cardiac lysate from MI mice. We injected MI mice, which were induced by a ligation of the left anterior descending coronary artery in C57BL/6 mice, twice with tDCs within 24 hours and at 7 days after the ligation.
Results—In vivo cardiac magnetic resonance imaging and ex vivo histology confirmed the beneficial effect on post-infarct LV remodeling in MI mice treated with tDCs. Subcutaneously administered infarct lysate-primed tDCs near the inguinal lymph node (LN) migrated to the regional LN and induced infarct tissue-specific Treg populations in the inguinal and mediastinal LNs, spleen, and infarcted myocardium, indicating that a local injection of tDCs induces a systemic activation of MI-specific Treg cells. These events elicited an inflammatory-to-reparative macrophage shift. The altered immune environment in the infarcted heart resulted in a better wound remodeling, preserved LV systolic function after myocardial tissue damage, and an improved survival.
Conclusions—This study showed that tDC therapy in a preclinical model of an MI was potentially translatable into an anti-remodeling therapy for ischemic tissue repair.
- Received April 22, 2016.
- Revision received December 1, 2016.
- Accepted January 20, 2017.