Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
Front Immunol. 2022 Jun 16;13:883733. doi: 10.3389/fimmu.2022.883733. eCollection 2022.
Immune checkpoint receptors are key players in regulating the immune response. They are responsible for both generating an immune response sufficient to kill invading pathogens, balancing the same response, and protecting against tissue destruction or the development of autoimmune events. The central role of the co-inhibitory receptors also referred to as inhibitory immune checkpoints, including PD-1 and CTLA-4 has become especially evident with the cancer treatments targeting these receptors. Blocking these pathways enhances the immune activity, resulting in both an increased chance of cancer clearance, at the same time induction of immune-related adverse events (irAE). Some of these irAE progress into actual autoimmune diseases with autoantibodies and symptoms, undistinguished from the naturally occurring diseases. This review will take advantage of the lessons learned from immune checkpoint blockade and relate this knowledge to our understanding of the same pathways in naturally occurring autoimmune diseases, mainly focusing on rheumatic diseases.
免疫检查点受体是调节免疫反应的关键因素。它们既能产生足以杀死入侵病原体的免疫反应，又能平衡这种反应，还能防止组织损伤或自身免疫事件的发生。共抑制受体（也称为抑制性免疫检查点）的核心作用，包括 PD-1 和 CTLA-4，在针对这些受体的癌症治疗中变得尤为明显。阻断这些途径会增强免疫活性，从而增加清除癌症的机会，同时也会引起免疫相关不良事件（irAE）。其中一些 irAE 进展为自身抗体和症状与自然发生的疾病相同的自身免疫性疾病。本综述将利用从免疫检查点阻断中获得的经验，并将这些知识与我们对自然发生的自身免疫性疾病中相同途径的理解联系起来，主要集中在风湿性疾病上。
