Downregulated cytotoxic CD8^(+)T-cell identifies with the NKG2A-soluble HLA-E axis as a predictive biomarker and potential therapeutic target in keloids  

作　　者：Heng Xu Zhu Zhu Jian Hu Jiawei Sun Yan Wo Xianshu Wang Hongzhi Zou Bin Li Yixin Zhang 

机构地区：[1]Department of Plastic and Reconstructive Surgery,Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China [2]Department of Biostatistics,Epidemiology and Informatics,University of Pennsylvania Perelman School of Medicine,Philadelphia,PA,USA [3]Genekinder Medicaltech(Shanghai)Co.,Ltd,Shanghai,China [4]Department of Anatomy and Physiology,School of Medicine,Shanghai Jiao Tong University,Shanghai,China [5]Creative Biosciences(Guangzhou)Co.,Ltd.,Guangzhou,Guangdong,China [6]Department of Colorectal Surgery,Guangdong Institute of Gastroenterology,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases,The Sixth Affiliated Hospital,Sun Yat-Sen University,Guangdong,China [7]Shanghai Institute of Immunology,Department of Immunology and Microbiology,Shanghai Jiao Tong University School of Medicine,Shanghai,China

出　　处：《Cellular & Molecular Immunology》2022年第4期527-539,共13页中国免疫学杂志（英文版）

基　　金：This study was funded by the National Natural Science Foundation of China(Nos.81772098,81672247,and 82002064);Shanghai Sailing Program(No.20YF1422700);Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support(No.20152227).

摘　　要：Keloids are an abnormal fibroproliferative wound-healing disease with a poorly understood pathogenesis,making it difficult to predict and prevent this disease in clinical settings.Identifying disease-specific signatures at the molecular and cellular levels in both the blood circulation and primary lesions is urgently needed to develop novel biomarkers for risk assessment and therapeutic targets for recurrence-free treatment.There is mounting evidence of immune cell dysregulation in keloid scarring.In this study,we aimed to profile keloid scar tissues and blood cells and found that downregulation of cytotoxic CD8^(+)T cells is a keloid signature in the peripheral blood and keloid lesions.Single-cell RNA sequencing revealed that the NKG2A/CD94 complex was specifically upregulated,which might contribute to the significant reduction in CTLs within the scar tissue boundary.In addition,the NKG2A/CD94 complex was associated with high serum levels of soluble human leukocyte antigen-E(sHLA-E).We subsequently measured sHLA-E in our hospital-based study cohort,consisting of 104 keloid patients,512 healthy donors,and 100 patients with an interfering disease.The sensitivity and specificity of sHLA-E were 83.69%(87/104)and 92.16%(564/612),respectively,and hypertrophic scars and other unrelated diseases exhibited minimal interference with the test results.Furthermore,intralesional therapy with triamcinolone combined with 5-fluorouracil drastically decreased the sHLA-E levels in keloid patients with better prognostic outcomes,while an incomplete reduction in the sHLA-E levels in patient serum was associated with higher recurrence.sHLA-E may effectively serve as a diagnostic marker for assessing the risk of keloid formation and a prognostic marker for the clinical outcomes of intralesional treatment.

关 键 词：KELOID Biomarker T cell immunology 

分 类 号：R392[医药卫生—免疫学]