PMID- 36839783
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230301
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 15
IP  - 2
DP  - 2023 Jan 30
TI  - CCR7 Mediates Dendritic-Cell-Derived Exosome Migration and Improves Cardiac 
      Function after Myocardial Infarction.
LID - 10.3390/pharmaceutics15020461 [doi]
LID - 461
AB  - 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.
FAU - Zhang, Youming
AU  - Zhang Y
AD  - Department of Cardiology, Qingpu Branch of Zhongshan Hospital, Fudan University, 
      Shanghai 201700, China.
AD  - Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji 
      University, Shanghai 200100, China.
FAU - Gao, Wei
AU  - Gao W
AD  - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan 
      University, Shanghai 200030, China.
FAU - Yuan, Jie
AU  - Yuan J
AD  - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan 
      University, Shanghai 200030, China.
FAU - Zhong, Xin
AU  - Zhong X
AD  - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan 
      University, Shanghai 200030, China.
FAU - Yao, Kang
AU  - Yao K
AD  - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan 
      University, Shanghai 200030, China.
FAU - Luo, Rong
AU  - Luo R
AD  - Department of Cardiology, Qingpu Branch of Zhongshan Hospital, Fudan University, 
      Shanghai 201700, China.
FAU - Liu, Haibo
AU  - Liu H
AUID- ORCID: 0000-0002-6999-8927
AD  - Department of Cardiology, Qingpu Branch of Zhongshan Hospital, Fudan University, 
      Shanghai 201700, China.
LA  - eng
GR  - 81400263/National Natural Science Foundation of China/
GR  - 81770350/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20230130
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC9964111
OTO - NOTNLM
OT  - CCR7
OT  - CD4+ T cells
OT  - dendritic cells
OT  - exosomes
OT  - myocardial infarction
COIS- The authors declare no conflict of interest.
EDAT- 2023/02/26 06:00
MHDA- 2023/02/26 06:01
PMCR- 2023/01/30
CRDT- 2023/02/25 04:17
PHST- 2022/11/01 00:00 [received]
PHST- 2023/01/15 00:00 [revised]
PHST- 2023/01/20 00:00 [accepted]
PHST- 2023/02/25 04:17 [entrez]
PHST- 2023/02/26 06:00 [pubmed]
PHST- 2023/02/26 06:01 [medline]
PHST- 2023/01/30 00:00 [pmc-release]
AID - pharmaceutics15020461 [pii]
AID - pharmaceutics-15-00461 [pii]
AID - 10.3390/pharmaceutics15020461 [doi]
PST - epublish
SO  - Pharmaceutics. 2023 Jan 30;15(2):461. doi: 10.3390/pharmaceutics15020461.