Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Int J Mol Sci. 2023 Jan 25;24(3):2338. doi: 10.3390/ijms24032338.
Soluble fibrinogen-like protein 2 (sFgl2), a novel effector of regulatory T cells (Tregs), has been demonstrated to have potent immunosuppressive functions. Multiple studies indicate that Tregs could exert important atheroprotective effects, but their numbers gradually decrease during atherogenesis. The receptor of sFgl2 can be expressed on Treg precursor cells, while the role of sFgl2 on Treg differentiation and atherosclerosis progression remains unclear. Firstly, we detected that the sFgl2 was decreased in humans and mice with atherosclerotic diseases and was especially lower in their vulnerable plaques. Then, we used both Adeno-associated virus-sFgl2 (AAV-sFgl2)-injected ApoE mice, which is systemic overexpression of sFgl2, and sFgl2ApoE bone marrow cells (BMC)-transplanted ApoE mice, which is almost immune-system-specific overexpression of sFgl2, to explore the role of sFgl2 in atherosclerosis. Our experiment data showed that AAV-sFgl2 and BMT-sFgl2 could reduce atherosclerotic area and enhance plaque stability. Mechanistically, sFgl2 increases the abundance and immunosuppressive function of Tregs, which is partly mediated by binding to FcγRIIB receptors and phosphorylating Smad2/3. Collectively, sFgl2 has an atheroprotective effect that is mainly achieved by forming a positive feedback pathway with Treg. sFgl2 and Treg could synergistically protect against atherosclerosis.
可溶性纤维蛋白样蛋白 2（sFgl2）是调节性 T 细胞（Tregs）的一种新型效应物，具有很强的免疫抑制功能。多项研究表明，Tregs 可以发挥重要的抗动脉粥样硬化作用，但在动脉粥样硬化发生过程中，其数量逐渐减少。sFgl2 的受体可以在 Treg 前体细胞上表达，而 sFgl2 对 Treg 分化和动脉粥样硬化进展的作用尚不清楚。首先，我们检测到患有动脉粥样硬化疾病的人和小鼠体内的 sFgl2 减少，而在易损斑块中尤其较低。然后，我们使用全身性过表达 sFgl2 的腺相关病毒-sFgl2（AAV-sFgl2）-注射 ApoE 小鼠和几乎是免疫系统特异性过表达 sFgl2 的 sFgl2ApoE 骨髓细胞（BMC）-移植 ApoE 小鼠来探索 sFgl2 在动脉粥样硬化中的作用。我们的实验数据表明，AAV-sFgl2 和 BMT-sFgl2 可以减少动脉粥样硬化面积并增强斑块稳定性。机制上，sFgl2 增加了 Tregs 的丰度和免疫抑制功能，部分是通过与 FcγRIIB 受体结合和磷酸化 Smad2/3 介导的。总之，sFgl2 具有抗动脉粥样硬化作用，主要通过与 Treg 形成正反馈途径来实现。sFgl2 和 Treg 可以协同保护免受动脉粥样硬化。
