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Circulation. 2017 Apr 11;135(15):1444-1457. doi: 10.1161/CIRCULATIONAHA.116.023106. Epub 2017 Feb 7.

Infarcted Myocardium-Primed Dendritic Cells Improve Remodeling and Cardiac Function After Myocardial Infarction by Modulating the Regulatory T Cell and Macrophage Polarization.

Author information

1
From Cardiology Division, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea (E.H.C., E.-H.P., H.E.P., T.-H.K., Y.-S.K., E.K., K.-B.S., K.K., K.C.); Department of Biotechnology, CHA University, Seongnam-si, Gyeonggi-do, Korea (J.-H.L., D.-S.L.); Pharos Vaccine Inc, Seongnam-si, Gyeonggido, Korea (J.-H.L., N.-C.J.); Division of Magnetic Resonance Research, Korea Basic Science Institute, Cheongju-si, Chungcheongbuk- do, Korea (C.P., K.-S.H.); Department of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences, Seoul (J.-Y.S.); and Department of Animal Biotechnology, Konkuk University, Seoul, Korea (H.G.S.).
2
From Cardiology Division, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea (E.H.C., E.-H.P., H.E.P., T.-H.K., Y.-S.K., E.K., K.-B.S., K.K., K.C.); Department of Biotechnology, CHA University, Seongnam-si, Gyeonggi-do, Korea (J.-H.L., D.-S.L.); Pharos Vaccine Inc, Seongnam-si, Gyeonggido, Korea (J.-H.L., N.-C.J.); Division of Magnetic Resonance Research, Korea Basic Science Institute, Cheongju-si, Chungcheongbuk- do, Korea (C.P., K.-S.H.); Department of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences, Seoul (J.-Y.S.); and Department of Animal Biotechnology, Konkuk University, Seoul, Korea (H.G.S.). kiyuk@catholic.ac.kr dslim@cha.ac.kr.

Abstract

BACKGROUND:

Inflammatory responses play a critical role in left ventricular remodeling after myocardial infarction (MI). Tolerogenic dendritic cells (tDCs) can modulate immune responses, inducing regulatory T cells in a number of inflammatory diseases.

METHODS:

We generated tDCs by treating bone marrow-derived dendritic cells with tumor necrosis factor-α and cardiac lysate from MI mice. We injected MI mice, 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 postinfarct left ventricular remodeling in MI mice treated with tDCs. Subcutaneously administered infarct lysate-primed tDCs near the inguinal lymph node migrated to the regional lymph node and induced infarct tissue-specific regulatory T-cell populations in the inguinal and mediastinal lymph nodes, spleen, and infarcted myocardium, indicating that a local injection of tDCs induces a systemic activation of MI-specific regulatory T 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 left ventricular systolic function after myocardial tissue damage, and improved survival.

CONCLUSIONS:

This study showed that tDC therapy in a preclinical model of MI was potentially translatable into an antiremodeling therapy for ischemic tissue repair.

KEYWORDS:

dendritic cells; heart failure; macrophage; myocardial infarction; regulatory T-cells; ventricular remodeling

[Indexed for MEDLINE]

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