STAT1功能获得性突变所致疾病研究进展
Research Progress in Diseases Caused by STAT1 Gain-of-Function Mutations
李琳鹏 1马靖 1谷昊 1舒洲 1毛华伟2
作者信息
- 1. 国家儿童医学中心首都医科大学附属北京儿童医院免疫科,北京 100045
- 2. 国家儿童医学中心首都医科大学附属北京儿童医院免疫科,北京 100045;国家儿童医学中心首都医科大学附属北京儿童医院儿科重大疾病研究教育部重点实验室出生缺陷遗传学研究北京市重点实验室,北京 100045
- 折叠
摘要
信号转导与转录激活因子1(STAT1)是STAT家族的重要成员之一,是一种关键的细胞质转录因子,同时也是JAK-STAT信号通路的重要组成部分.STAT1功能获得性(GOF)突变会使STAT1蛋白去磷酸化障碍,从而介导细胞对Ⅰ、Ⅱ和Ⅲ型干扰素(IFN)和白细胞介素-27(IL-27)、IL-6、IL-10、IL-17等多种细胞信号通路的增强并抑制Th17细胞.STAT1-GOF突变临床表现多样,包括慢性黏膜皮肤念珠菌病为主的感染性疾病及自身免疫性疾病.对于STAT1-GOF的治疗,如针对STATI过度磷酸化应用芦可替尼的靶向治疗,对不同自身免疫受累系统应用免疫调节治疗及造血干细胞移植等可取得一定疗效.随着对于疾病机制的认识和新临床表型的发现,本文聚焦STAT1-GOF所致疾病,介绍其临床表现及治疗进展,以促进对此类疾病的认识及其未来的诊治和研究.
Abstract
Signal transduction and activator of transcription factor 1(STAT1),one of the important members of the STAT family,is a key cytoplasmic transcription factor and an important component of the JAK-STAT signaling pathway.Gain-of-function mutations in STAT1(STAT1-GOF)impaired the dephos-phorylation of STAT1 protein,mediated the enhancement of cell signaling pathways such as type Ⅰ,Ⅱ,and Ⅲ interferon(IFN)and interleukins-27(IL-27),IL-6,IL-10,and IL-17,and inhibited Th17 cells.The clinical manifestations of STAT1-GOF are diverse,including chronic mucocutaneous candidiasis and autoimmune diseases.For the treatment of STAT1-GOF,such as targeted therapy with ruxolitinib for STAT1 hyperphosphorylation,immunomodulatory therapy and hematopoietic stem cell transplantation for different self-immune systems,certain curative effects can be obtained.With the understanding of disease mechanisms and the discovery of new clinical phenotypes,this review focuses on the diseases caused by gain-of-function mutations of STAT1,and introduces the clinical manifestations and treatment progress of STAT1-GOF to promote the understanding of such diseases and their future diagnosis,treatment and re-search works.
关键词
原发性免疫缺陷病/STAT1功能获得性突变/慢性黏膜皮肤念珠菌病/Th17细胞Key words
primary immunodeficiency disease/STAT1 gain-of-function mutations/chronic mucocutaneous candidiasis/Th17 cells引用本文复制引用
出版年
2024
NETL
NSTL
万方数据