Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674, USA.
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Metabolic, and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1674, USA.
Immunity. 2019 Apr 16;50(4):832-850. doi: 10.1016/j.immuni.2019.03.028.
The common cytokine receptor γ chain, γ, is a component of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. Mutation of the gene encoding γ results in X-linked severe combined immunodeficiency in humans, and γ family cytokines collectively regulate development, proliferation, survival, and differentiation of immune cells. Here, we review the basic biology of these cytokines, highlighting mechanisms of signaling and gene regulation that have provided insights for immunodeficiency, autoimmunity, allergic diseases, and cancer. Moreover, we discuss how studies of this family stimulated the development of JAK3 inhibitors and present an overview of current strategies targeting these pathways in the clinic, including novel antibodies, antagonists, and partial agonists. The diverse roles of these cytokines on a range of immune cells have important therapeutic implications.
共同的细胞因子受体γ链，γ，是白细胞介素-2（IL-2）、IL-4、IL-7、IL-9、IL-15 和 IL-21 受体的组成部分。编码γ的基因突变导致人类 X 连锁严重联合免疫缺陷，γ 家族细胞因子共同调节免疫细胞的发育、增殖、存活和分化。在这里，我们回顾了这些细胞因子的基本生物学特性，强调了信号转导和基因调控的机制，这些机制为免疫缺陷、自身免疫、过敏疾病和癌症提供了见解。此外，我们还讨论了该家族的研究如何刺激 JAK3 抑制剂的发展，并概述了目前在临床上针对这些途径的策略，包括新型抗体、拮抗剂和部分激动剂。这些细胞因子在一系列免疫细胞上的多种作用具有重要的治疗意义。
