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TIMD4hiMHCⅡhi Macrophages Preserve Heart Function Through Retnla
Danyang Zhang1,2,3, Xuanhao Wang1,2,3, Lianlian Zhu1,2,3
1Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
JACC. Basic to Translational Science
|February 5, 2025
Summary
Resident macrophages expressing TIMD4 and MHC class II (TIMD4hiMHCⅡhi) are crucial for heart health. Their signature gene, Retnla (resistin-like alpha), protects against heart failure progression.
Area of Science:
- Immunology
- Cardiology
- Molecular Biology
Background:
- Macrophages play diverse roles in cardiovascular health and disease.
- Specific macrophage subsets with unique functions are increasingly being identified in the heart.
Purpose of the Study:
- To characterize the TIMD4hiMHCⅡhi macrophage subset in the heart.
- To investigate the role of Retnla (resistin-like alpha) in heart failure.
Main Methods:
- Genetic fate mapping to trace macrophage origins.
- Single-cell RNA sequencing to identify gene expression profiles.
- Experimental models of heart failure with genetic manipulation of macrophages and Retnla.
Main Results:
- Genetic fate mapping confirmed TIMD4hiMHCⅡhi macrophages as resident cardiac macrophages.
- Single-cell RNA sequencing identified Retnla as a signature gene for this subset.
- Administration of RELMα protein delayed heart failure onset.
- Deletion of TIMD4hiMHCⅡhi macrophages or loss of Retnla accelerated heart failure progression.
Conclusions:
- TIMD4hiMHCⅡhi macrophages are essential resident cardiac macrophages.
- Retnla is a key protective gene expressed by these macrophages in heart failure.
- Targeting this macrophage subset or Retnla may offer therapeutic strategies for heart failure.
