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CCR7 Mediates Dendritic-Cell-Derived Exosome Migration and Improves Cardiac Function after Myocardial Infarction

Authors :
Youming Zhang
Wei Gao
Jie Yuan
Xin Zhong
Kang Yao
Rong Luo
Haibo Liu
Source :
Pharmaceutics, Vol 15, Iss 2, p 461 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

Dendritic cells (DCs) play key roles in promoting wound healing after myocardial infarction (MI). Our previous studies have shown that exosomes derived from DCs (DEXs) could migrate to lymphoid tissue and improve cardiac function post-MI by activating CD4+ T cells; however, the mechanism of DEXs’ migration to lymphoid tissue and the improvement of cardiac function are still unknown. In our study, we found that CCR7 expression significantly increased in MI-DEXs compared with control-DEXs; meanwhile, CCL19 and CCL21, the ligands of CCR7, significantly increased in the serum of MI-model mice. Subsequently, we overexpressed and knocked down CCR7 in MI-DEXs and found that overexpressed CCR7 enhanced the migration of MI-DEXs to the spleen; however, CCR7 knockdown attenuated MI-DEXs’ migration according to near-IR fluorescence imaging. Furthermore, overexpressed CCR7 in MI-DEXs enhanced the MI-DEXs’ improvement of cardiac function after MI; however, CCR7-knockdown MI-DEXs attenuated this improvement. In addition, after DEXs’ migration to the spleen, MI-DEXs activated CD4+ T cells and induced the expression of IL-4 and IL-10, which were significantly increased in the MI-DEX group compared with the control group. In conclusion, CCR7 could mediate DEXs’ migration to the spleen and improve cardiac function after MI, and we found that the mechanism was partly via activation of CD4+ T cells and secretion of IL-4 and IL-10. Our study presented an innovative method for improving cardiac function by enhancing the migration ability of MI-DEXs after MI, while CCR7 could be a potential candidate for MI-DEX bioengineering to enhance migration.

Details

Language :
English
ISSN :
19994923
Volume :
15
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.47f24a05933442c99b085cf72819aeb
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics15020461