Zhang Qianxia, Vignali Dario A A
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.
Immunity. 2016 May 17;44(5):1034-51. doi: 10.1016/j.immuni.2016.04.017.
The immune system is guided by a series of checks and balances, a major component of which is a large array of co-stimulatory and co-inhibitory pathways that modulate the host response. Although co-stimulation is essential for boosting and shaping the initial response following signaling through the antigen receptor, inhibitory pathways are also critical for modulating the immune response. Excessive co-stimulation and/or insufficient co-inhibition can lead to a breakdown of self-tolerance and thus to autoimmunity. In this review, we will focus on the role of co-stimulatory and co-inhibitory pathways in two systemic (systemic lupus erythematosus and rheumatoid arthritis) and two organ-specific (multiple sclerosis and type 1 diabetes) emblematic autoimmune diseases. We will also discuss how mechanistic analysis of these pathways has led to the identification of potential therapeutic targets and initiation of clinical trials for autoimmune diseases, as well as outline some of the challenges that lie ahead.
免疫系统由一系列制衡机制引导，其中一个主要组成部分是大量调节宿主反应的共刺激和共抑制途径。虽然共刺激对于通过抗原受体发出信号后的初始反应的增强和塑造至关重要，但抑制途径对于调节免疫反应也至关重要。过度的共刺激和/或共抑制不足会导致自身耐受性的破坏，从而引发自身免疫。在本综述中，我们将重点关注共刺激和共抑制途径在两种全身性（系统性红斑狼疮和类风湿性关节炎）和两种器官特异性（多发性硬化症和1型糖尿病）标志性自身免疫疾病中的作用。我们还将讨论对这些途径的机制分析如何导致自身免疫疾病潜在治疗靶点的识别和临床试验的启动，并概述未来面临的一些挑战。
