Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
MRC Toxicology Unit, Gleeson Building, Tennis Court Road, Cambridge, UK.
Curr Opin Immunol. 2021 Oct;72:135-145. doi: 10.1016/j.coi.2021.04.007. Epub 2021 May 24.
The IL-6 family of cytokines mediates functions in host protective immunity, development of multiple organs, tissue regeneration and metabolism. Inborn errors in cytokines or cytokine receptor units highlight specific roles for IL-6, IL-11, LIF, OSM, and CLC signaling whereas incomplete loss-of-function variants in the common receptor chain GP130 encoded by IL6ST or the transcription factor STAT3, as well as genes that affect either GP130 glycosylation (PGM3) or STAT3 transcriptional control (ZNF341) lead to complex phenotypes including features of hyper-IgE syndrome. Gain-of-function variants in the GP130-STAT3 signaling pathway cause immune dysregulation disorders. Insights into IL-6 family cytokine signaling inform on therapeutic application in immune-mediated disorders and potential side effects such as infection susceptibility.
白细胞介素 6 家族细胞因子介导宿主保护性免疫、多种器官发育、组织再生和代谢的功能。细胞因子或细胞因子受体单位的先天性错误突出了白细胞介素 6、白细胞介素 11、白血病抑制因子、抑瘤素 M 和 CLC 信号的特定作用，而编码白细胞介素 6 刺激因子的共同受体链 GP130 中的不完全功能丧失变体或转录因子 STAT3，以及影响 GP130 糖基化（PGM3）或 STAT3 转录控制（ZNF341）的基因导致复杂的表型，包括高免疫球蛋白 E 综合征的特征。GP130-STAT3 信号通路的获得性功能变体导致免疫失调紊乱。对白细胞介素 6 家族细胞因子信号的深入了解为免疫介导的疾病提供了治疗应用，并可能产生感染易感性等潜在副作用。
