During host immune response, an initial and sufficient activation is required to avoid infection and cancer, yet an excessive activation bears the risk of autoimmune reactivity and disease development. This fastidious balance of the immune system is regulated by co-stimulatory and co-inhibitory molecules, also known as immune checkpoints. Both excessive co-stimulation and insufficient co-inhibition can induce the activation and proliferation of autoreactive cells that may lead to the development of autoimmune diseases. During the last decade, a growing number of new immune checkpoint receptors and ligands have been discovered, providing an attractive approach to investigate their implication in the pathogenesis of autoimmune diseases and their potential role as targets for effective therapeutic interventions. In this review, we focus on the roles and underlying mechanisms of co-stimulatory and co-inhibitory receptors and other molecules that function as immune checkpoints in autoimmune diseases such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, Sjögren's syndrome, type I diabetes and inflammatory bowel disease. We also summarize previous and current clinical trials targeting these checkpoint pathways in autoimmune diseases and discuss further therapeutic implications and possible risks and challenges.

中文翻译：

---

免疫检查点分子。自身免疫性疾病未来可能的治疗意义。

在宿主免疫应答期间，需要初始且充分的活化来避免感染和癌症，但是过度活化具有自身免疫反应性和疾病发展的风险。免疫系统的这种平衡平衡受共同刺激和共同抑制分子（也称为免疫检查点）的调节。过度共刺激和共抑制不足均可诱导自身反应性细胞的活化和增殖，这可能导致自身免疫性疾病的发展。在过去的十年中，发现了越来越多的新型免疫检查点受体和配体，为研究它们在自身免疫性疾病发病机理中的意义以及作为有效治疗干预目标的潜在作用提供了一种有吸引力的方法。在这篇评论中，我们重点研究在自身免疫性疾病（例如系统性红斑狼疮，多发性硬化症，类风湿性关节炎，干燥综合征，I型糖尿病和炎性肠病）中自身免疫疾病的共刺激和共抑制受体以及其他分子的作用和潜在机制。我们还总结了针对自身免疫性疾病中这些检查点途径的先前和当前的临床试验，并讨论了进一步的治疗意义以及可能的风险和挑战。