Details

Autor(en) / Beteiligte

• Liu, Haibo
• Gao, Wei
• Yuan, Jie
• Wu, Chaoneng
• Yao, Kang
• Zhang, Li
• Ma, Leilei
• Zhu, Jianbing
• Zou, Yunzeng
• Ge, Junbo

Titel

Exosomes derived from dendritic cells improve cardiac function via activation of CD4+ T lymphocytes after myocardial infarction

Ist Teil von

• Journal of molecular and cellular cardiology, 2016-02, Vol.91, p.123-133

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract CD4+ T cell activation plays a key role in facilitating wound healing after myocardial infarction (MI). Exosomes (EXs) secreted from dendritic cells (DCs) can activate T cells in tumor models ; however, whether DEXs (DC-EXs) can mediate CD4+ T cell activation and improve wound healing post-MI remains unknown. This study sought to determine whether DEXs mediate CD4+ T cell activation and improve cardiac function post-MI in mice. We used supernatants of hypoxic primary or necrotic HL-1 cardiomyocytes to simulate the post-MI cardiomyocyte microenvironment in vitro . Cultured bone marrow-derived DCs (BMDCs) from mice were stimulated with the supernatants of normal (Control group), hypoxic primary or necrotic HL-1 cardiomyocytes (MI group); a subset of BMDCs remained unstimulated (Negative group). DEXs were then isolated from the BMDC supernatants and either incubated with CD4+ T cells or injected into mice via the tail vein. In this study, we found that the supernatants of both hypoxic primary and necrotic HL-1 cardiomyocytes upregulate DC maturation markers. After the injection of DEXs, a greater number of MI-DEXs are recruited by the mouse spleen and with greater rapidity than control- or negative-DEXs. Confocal imaging and flow cytometry revealed that MI-DEXs exhibited higher uptake by splenic CD4+ T cells than the control- and negative-DEXs, and this increase was correlated with significantly greater increases in the expression of chemokines and the inflammatory cytokines IFN-γ and TNF by the CD4+ T cells in vitro and in vivo . In addition, the injection of MI-DEXs improved cardiac function in mice post-MI. These results suggest that DEXs could mediate the activation of CD4+ T cells through an endocrine mechanism and improve cardiac function post-MI. Our findings provide the basis for a novel strategy for the treatment of MI through the systemic delivery of DEXs.