Wang Bing, Zhang Biqing, Wu Min, Xu Ting
Department of Rheumatology and Immunology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China.
J Transl Autoimmun. 2024 Jul 27;9:100249. doi: 10.1016/j.jtauto.2024.100249. eCollection 2024 Dec.
Systemic lupus erythematosus (SLE) represents an autoimmune disorder that affects multiple systems. In the treatment of this condition, the focus primarily revolves around inflammation suppression and immunosuppression. Consequently, targeted therapy has emerged as a prevailing approach. Currently, the quest for highly sensitive and specifically effective targets has gained significant momentum in the context of SLE treatment. Lymphocyte activation gene-3 (LAG-3) stands out as a crucial inhibitory receptor that binds to pMHC-II, thereby effectively dampening autoimmune responses. Fibrinogen-like protein 1 (FGL1) serves as the principal immunosuppressive ligand for LAG-3, and their combined action demonstrates a potent immunosuppressive effect. This intricate mechanism paves the way for potential SLE treatment by targeting LAG-3 with FGL1. This work provides a comprehensive summary of LAG-3's role in the pathogenesis of SLE and elucidates the feasibility of leveraging FGL1 as a therapeutic approach for SLE management. It introduces a novel therapeutic target and opens up new avenues of therapeutic consideration in the clinical context of SLE treatment.
系统性红斑狼疮(SLE)是一种影响多个系统的自身免疫性疾病。在这种疾病的治疗中,重点主要围绕炎症抑制和免疫抑制。因此,靶向治疗已成为一种主流方法。目前,在SLE治疗背景下,寻找高度敏感且特效的靶点已成为重要趋势。淋巴细胞激活基因-3(LAG-3)是一种关键的抑制性受体,可与pMHC-II结合,从而有效抑制自身免疫反应。纤维蛋白原样蛋白1(FGL1)是LAG-3的主要免疫抑制配体,它们的联合作用显示出强大的免疫抑制效果。这种复杂机制为通过FGL1靶向LAG-3治疗SLE提供了可能。这项工作全面总结了LAG-3在SLE发病机制中的作用,并阐明了利用FGL1作为SLE治疗方法的可行性。它引入了一个新的治疗靶点,并在SLE治疗的临床背景下开辟了新的治疗思路。