The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multi...The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.展开更多
背景:既往研究提示免疫细胞亚型与心血管疾病风险相关,但由于混杂因素的影响,他们之间的因果关系尚不明确。目的:评估免疫细胞亚型与心血管疾病之间的潜在因果关系。方法:研究数据来源主要涉及3个数据库:GWAS Catalog是由美国国家人类...背景:既往研究提示免疫细胞亚型与心血管疾病风险相关,但由于混杂因素的影响,他们之间的因果关系尚不明确。目的:评估免疫细胞亚型与心血管疾病之间的潜在因果关系。方法:研究数据来源主要涉及3个数据库:GWAS Catalog是由美国国家人类基因组研究所和欧洲生物信息学研究所共同维护的数据库,UK biobank是由英国政府及惠康基金会支持的英国人群基因组、健康及疾病表型数据库,IEU OpenGWAS是由英国布里托斯大学MRC流行病学单元开发的以欧洲人群为主的GWAS数据库,均为开放数据库,研究已获得相关机构审查委员会批准。以731个免疫细胞表型作为暴露因素,以7种心血管疾病(心房颤动、扩张型心肌病、冠状动脉粥样硬化性心脏病、心力衰竭、肥厚型心肌病、高血压及瓣膜性心脏病)作为结局因素,进行双样本孟德尔随机化分析,主要使用逆方差加权和加权中位数方法进行孟德尔随机化分析和敏感性分析,评估异质性和多效性。结果与结论:①经错误发现率校正后,免疫表型对心房颤动和高血压具有统计学显著影响。5种细胞类型与心房颤动风险相关,包括CD11c on monocytes(OR=0.917,95%CI:0.876-0.960)、FSC-A on myeloid dendritic cells(OR=0.942,95%CI:0.910-0.974)、CX3CR1 on CD14^(+)CD16^(-)monocytes(OR=1.045,95%CI:1.022-1.070)、CX3CR1 on monocytes(OR=1.050,95%CI:1.024-1.076)以及CX3CR1 on CD14^(+)CD16^(+)monocytes(OR=1.050,95%CI:1.024-1.077)。筛选出3种对高血压具有保护作用的免疫表型:CD19 on switched memory B cells(OR=0.986,95%CI:0.980-0.993)、CD25^(+)+CD8^(+)T cells(OR=0.993,95%CI:0.990-0.997)和CD25^(+)+CD8^(+)T cells绝对值计数(OR=0.993,95%CI:0.989-0.996)。在敏感性分析中均未观察到潜在的异质性或水平多效性。②研究发现4种单核细胞和1种髓样树突状细胞与心房颤动之间有因果关系,1种记忆B细胞和2种T细胞与高血压之间存在潜在因果关系,提示监测和治疗心房颤动、高血压时考虑免疫细胞表型的必要性。此次研究采用公共数据库进行分析,为中国人群免疫细胞亚群和心血管疾病的相关研究提供了参考,同时为国人进一步防治心房颤动和高血压提供借鉴。展开更多
基金supported by the National Natural Science Foundational of China(Key Program),No.U24A20692(to CJZ)the National Natural Science Foundational of China,Nos.82101414(to MLJ),82371355(to CJZ)+4 种基金the National Natural Science Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovation and Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’s Hospital,No.30420230005(to CJZ)Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(to CJZ)。
文摘The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.
文摘背景:既往研究提示免疫细胞亚型与心血管疾病风险相关,但由于混杂因素的影响,他们之间的因果关系尚不明确。目的:评估免疫细胞亚型与心血管疾病之间的潜在因果关系。方法:研究数据来源主要涉及3个数据库:GWAS Catalog是由美国国家人类基因组研究所和欧洲生物信息学研究所共同维护的数据库,UK biobank是由英国政府及惠康基金会支持的英国人群基因组、健康及疾病表型数据库,IEU OpenGWAS是由英国布里托斯大学MRC流行病学单元开发的以欧洲人群为主的GWAS数据库,均为开放数据库,研究已获得相关机构审查委员会批准。以731个免疫细胞表型作为暴露因素,以7种心血管疾病(心房颤动、扩张型心肌病、冠状动脉粥样硬化性心脏病、心力衰竭、肥厚型心肌病、高血压及瓣膜性心脏病)作为结局因素,进行双样本孟德尔随机化分析,主要使用逆方差加权和加权中位数方法进行孟德尔随机化分析和敏感性分析,评估异质性和多效性。结果与结论:①经错误发现率校正后,免疫表型对心房颤动和高血压具有统计学显著影响。5种细胞类型与心房颤动风险相关,包括CD11c on monocytes(OR=0.917,95%CI:0.876-0.960)、FSC-A on myeloid dendritic cells(OR=0.942,95%CI:0.910-0.974)、CX3CR1 on CD14^(+)CD16^(-)monocytes(OR=1.045,95%CI:1.022-1.070)、CX3CR1 on monocytes(OR=1.050,95%CI:1.024-1.076)以及CX3CR1 on CD14^(+)CD16^(+)monocytes(OR=1.050,95%CI:1.024-1.077)。筛选出3种对高血压具有保护作用的免疫表型:CD19 on switched memory B cells(OR=0.986,95%CI:0.980-0.993)、CD25^(+)+CD8^(+)T cells(OR=0.993,95%CI:0.990-0.997)和CD25^(+)+CD8^(+)T cells绝对值计数(OR=0.993,95%CI:0.989-0.996)。在敏感性分析中均未观察到潜在的异质性或水平多效性。②研究发现4种单核细胞和1种髓样树突状细胞与心房颤动之间有因果关系,1种记忆B细胞和2种T细胞与高血压之间存在潜在因果关系,提示监测和治疗心房颤动、高血压时考虑免疫细胞表型的必要性。此次研究采用公共数据库进行分析,为中国人群免疫细胞亚群和心血管疾病的相关研究提供了参考,同时为国人进一步防治心房颤动和高血压提供借鉴。
