When the heart calls for help: Clusterin reprograms immunity to enable regeneration

Shih-Lei Ben Lai; Yu-Jen Hung; Rubén Marín-Juez

doi:10.1016/j.stem.2025.10.010

When the heart calls for help: Clusterin reprograms immunity to enable regeneration

Cell Stem Cell. 2025 Dec 4;32(12):1793-1795. doi: 10.1016/j.stem.2025.10.010.

Authors

Shih-Lei Ben Lai¹, Yu-Jen Hung², Rubén Marín-Juez³

Affiliations

¹ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan. Electronic address: ben.s.lai@ibms.sinica.edu.tw.
² Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.
³ Centre de Recherche Azrieli, Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC, Canada; Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.

PMID: 41349521
DOI: 10.1016/j.stem.2025.10.010

Abstract

Adult mammalian hearts exhibit limited regenerative capacity. Fan et al.¹ report that neonatal cardiomyocyte-derived clusterin competes for macrophage Toll-like receptor 4 to suppress inflammation and induces reparative polarization. This cardio-immune dialogue activates BMP2 signaling to stimulate cardiomyocyte proliferation, reframing inflammation as a cooperative driver of heart repair.

MeSH terms

Animals
Clusterin* / metabolism
Heart* / physiology
Humans
Mice
Myocytes, Cardiac / cytology
Myocytes, Cardiac / metabolism
Regeneration*
Signal Transduction
Toll-Like Receptor 4 / metabolism

Substances

Clusterin
Toll-Like Receptor 4