Key result
CCR7-overexpressing dendritic cell exosomes improve post-MI cardiac function via splenic CD4+ T-cell activation.
Why the study?
The mechanisms underlying dendritic-cell-derived exosome migration to lymphoid tissue and improvement of cardiac function after myocardial infarction were unknown.
Does CCR7 modification in dendritic-cell-derived exosomes improve their migration and cardiac function in a mouse model of myocardial infarction?
Does CCR7 modification in dendritic-cell-derived exosomes improve their migration and cardiac function in a mouse model of myocardial infarction?
CCR7 mediates the migration of dendritic-cell-derived exosomes to the spleen and improves cardiac function post-MI, suggesting a potential bioengineering target for MI therapy.
Answers are grounded in this paper and cite their sources.
Does not support clinical use of CCR7-modified exosomes; hypothesis-generating for bioengineered exosome therapies post-MI.
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.
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Zhang et al. (2023) studied Myocardial infarction. CCR7-overexpressed MI-DEXs vs. Sham, saline (MI group), normal DEXs, unmodified MI-DEXs, or CCR7-knockdown MI-DEXs was evaluated on Cardiac function (percent fractional shortening and ejection fraction) and DEX migration to the spleen. Overexpression of CCR7 in dendritic cell-derived exosomes enhanced their migration to the spleen and improved cardiac function after myocardial infarction via activation of CD4+ T cells.
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