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sFgl2-Treg Positive Feedback Pathway Protects against Atherosclerosis
Tianhui An1, Mengyuan Guo2, Cheng Fan1,3
1Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
International Journal of Molecular Sciences
|February 11, 2023
Summary
Soluble fibrinogen-like protein 2 (sFgl2) protects against atherosclerosis by boosting regulatory T cells (Tregs). This study reveals sFgl2 enhances Treg function, reducing plaque size and improving stability in mouse models.
Area of Science:
- Immunology
- Cardiovascular Biology
- Molecular Medicine
Background:
- Regulatory T cells (Tregs) have atheroprotective effects, but their numbers decrease during atherosclerosis.
- Soluble fibrinogen-like protein 2 (sFgl2) is an immunosuppressive molecule, but its role in Treg differentiation and atherosclerosis is unclear.
Purpose of the Study:
- To investigate the role of sFgl2 in atherosclerosis progression.
- To elucidate the mechanism by which sFgl2 influences Tregs and plaque stability.
Main Methods:
- Measured sFgl2 levels in human and mouse atherosclerotic plaques.
- Utilized Adeno-associated virus-sFgl2 (AAV-sFgl2) and sFgl2 transgenic bone marrow cell transplantation (BMT-sFgl2) in ApoE-/- mice to overexpress sFgl2.
- Analyzed atherosclerotic area, plaque stability, Treg abundance, and immunosuppressive function, and FcγRIIB/Smad2/3 signaling.
Main Results:
- sFgl2 levels were decreased in atherosclerotic individuals and mice, particularly in vulnerable plaques.
- Overexpression of sFgl2 (AAV-sFgl2 and BMT-sFgl2) reduced atherosclerotic area and enhanced plaque stability.
- sFgl2 increased Treg abundance and immunosuppressive function, mediated by FcγRIIB receptor binding and Smad2/3 phosphorylation.
Conclusions:
- sFgl2 exhibits atheroprotective effects by enhancing Treg function and stability.
- A positive feedback loop between sFgl2 and Tregs synergistically protects against atherosclerosis.
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