Department of Biochemistry and Immunology, Institute of Biological Science, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, New South Wales, Australia.
Cell Immunol. 2022 Feb;372:104476. doi: 10.1016/j.cellimm.2021.104476. Epub 2022 Jan 10.
Rheumatoid arthritis(RA) is a debilitating chronic inflammatory disease. Suppressors of Cytokine Signaling(SOCS) proteins regulate homeostasis and pathogenesis in several diseases. The intersection between RA pathophysiology and SOCS2 is unclear. Herein, we investigated the roles of SOCS2 during the development of an experimental antigen-induced arthritis(AIA). In wild type mice, joint SOCS2 expression was reduced during AIA development. At the peak of inflammation, SOCS2 mice presented with reduced numbers of infiltrated cells in their joints. At the late phase of AIA, however, exhibited increased adhesion/infiltration of neutrophils, macrophages, CD4-T cells, CD4CD8-T cells, and CD4CD8-T cells associated with elevated IL-17 and IFN-γ levels, joint damage, proteoglycan loss, and nociception. SOCS2 deficiency resulted in lower numbers of apoptotic neutrophils and reduced efferocytosis. The present study demonstrated the vital role of SOCS2 during the development and resolution of an experimental RA model. Hence, this protein may be a novel therapeutic target for this disorder.
类风湿关节炎（RA）是一种使人虚弱的慢性炎症性疾病。细胞因子信号转导抑制剂（SOCS）蛋白调节着几种疾病的体内平衡和发病机制。RA 病理生理学和 SOCS2 之间的交叉点尚不清楚。在此，我们研究了 SOCS2 在实验性抗原诱导关节炎（AIA）发展过程中的作用。在野生型小鼠中，关节 SOCS2 的表达在 AIA 发展过程中减少。在炎症高峰期，SOCS2 小鼠关节中的浸润细胞数量减少。然而，在 AIA 的后期阶段，表现出中性粒细胞、巨噬细胞、CD4-T 细胞、CD4CD8-T 细胞和 CD4CD8-T 细胞的黏附/浸润增加，同时伴随着 IL-17 和 IFN-γ水平升高、关节损伤、蛋白聚糖丢失和疼痛。SOCS2 缺乏导致凋亡中性粒细胞数量减少和吞噬作用降低。本研究证明了 SOCS2 在实验性 RA 模型的发展和消退过程中的重要作用。因此，该蛋白可能是该疾病的一个新的治疗靶点。
