Current Opinion in Immunology ( IF 7 ) Pub Date : 2020-06-30 , DOI: 10.1016/j.coi.2020.06.001 Stephanie Grebinoski 1 , Dario Aa Vignali 2
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.
中文翻译:
抑制性受体激动剂:自身免疫性疾病疗法的未来?
中枢耐受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由外周和/或中枢耐受机制的严重缺陷或限制引起,为治疗干预提供了机会。最近的进展突显了抑制性受体 (IR) 在自身免疫中的重大影响,其介导外周耐受。小鼠的缺失和阻断研究、人类的 IR 破坏以及与阳性疾病结果的相关性都强调了增强 IR 信号(激动)——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。尽管关键问题仍然存在,但 IR 激动剂代表了治疗自身免疫性疾病和炎症性疾病的一个未被重视和未开发的机会。