抑制性受体激动剂：自身免疫性疾病治疗的未来？
Inhibitory receptor agonists: the future of autoimmune disease therapeutics?
机构信息
Department of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA; Graduate Program of Microbiology and Immunology, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA 15213, USA.
Department of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
出版信息
Curr Opin Immunol. 2020 Dec;67:1-9. doi: 10.1016/j.coi.2020.06.001. Epub 2020 Jun 30.
Central and peripheral tolerance both contribute to protection against autoimmunity. The pathogenesis of autoimmunity, however, can result from critical deficits or limitations in peripheral and/or central tolerance mechanisms, presenting an opportunity for therapeutic intervention. Recent advances highlight the substantial impact of inhibitory receptors (IRs), which mediate peripheral tolerance, in autoimmunity. Deletion and blockade studies in mice, IR disruption in humans, and correlation with positive disease outcomes all highlight potential clinical benefits of enhancing IR signaling (agonism)-specifically CTLA4, PD1, LAG3, TIM3 and TIGIT-to treat autoimmune disease. Although critical questions remain, IR agonists represent an unappreciated and untapped opportunity for the treatment of autoimmune and inflammatory diseases.
中枢和外周耐受都有助于防止自身免疫。然而，自身免疫的发病机制可能是由于外周和/或中枢耐受机制的严重缺陷或限制所致，为治疗干预提供了机会。最近的进展强调了抑制性受体 (IRs) 在自身免疫中的重要作用，IRs 介导外周耐受。在小鼠中进行的缺失和阻断研究、人类中的 IR 破坏以及与阳性疾病结果的相关性都突出了增强 IR 信号（激动剂）——特别是 CTLA4、PD1、LAG3、TIM3 和 TIGIT——治疗自身免疫性疾病的潜在临床益处。尽管仍存在关键问题，但 IR 激动剂代表了治疗自身免疫和炎症性疾病的一个未被充分认识和利用的机会。
Zotero 插件