VSIG3 preserves mitochondrial homeostasis and restrains CD4⁺ T-Cell infiltration in myocardial ischemia-reperfusion injury through regulation of mitochondrial-derived vesicles.

Authors

Jian Hou, Liqun Shang, Zi Yan, Yuanhan Ao, Wanying Chen, Pei Lin, Jiarui Liu, Xintong Wang, Zhaojin Li, Huayang Li, Quan Liu, Yi Zhang, Jianping Yao, Can Gao, Junyou Zhu, Shiyu Li, Suiqing Huang, Zhongkai Wu

Published in

Journal of nanobiotechnology. Jul 13, 2026. Epub Jul 13, 2026.

Abstract

Myocardial ischemia-reperfusion (MI/R) injury remains an inevitable and severe clinical challenge during cardiac surgery, primarily characterized by mitochondrial dysfunction and robust CD4⁺ T cell infiltration. In this study, we investigated the therapeutic potential of the immune checkpoint molecule VSIG3 (V-set and transmembrane domain-containing protein 3) in mitigating MI/R injury. In clinical samples, ELISA-detectable VSIG3-related plasma immunoreactivity of an undefined molecular form was associated with myocardial injury and inflammation. Recombinant VSIG3 administration improved cardiac function in MI/R mice and was accompanied by lower cardiac extracellular vesicle (EV) levels, including a reduction in TOMM20⁺ mitochondrial-derived vesicle (MDV)-related signals. In vitro, VSIG3 attenuated apoptosis, enhanced antioxidant capacity, and preserved mitochondrial metabolism, accompanied by an associated increase in PI3K/Akt/mTOR phosphorylation at 3 h post-injury. Exogenous MDV supplementation partially counteracted the cytoprotective effects observed with VSIG3 treatment. In vivo, VSIG3 treatment reduced CD4⁺ T cell infiltration and suppressed inflammatory cytokines (TNF-α, IL-17α, IL-21) in myocardial tissue. In summary, exogenous MDVs behaved as detrimental stimuli in the present experimental settings, whereas VSIG3 treatment was accompanied by reduced MDV release, improved mitochondrial homeostasis, and suppressed T-cell activation. These findings support an association between VSIG3 treatment and MDV-related changes in MI/R injury, but do not establish MDV suppression as a necessary or sufficient mediator of VSIG3-mediated cardioprotection.

PMID:
42443902
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.