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

引用

cellular & Molecular immunology 2022年第4期19卷 527-539页

作者： Heng Xu Zhu Zhu Jian Hu Jiawei Sun Yan Wo Xianshu Wang Hongzhi Zou Bin Li Yixin Zhang Department of Plastic and Reconstructive Surgery Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Biostatistics Epidemiology and InformaticsUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPAUSA Genekinder Medicaltech(Shanghai)Co. LtdShanghaiChina Department of Anatomy and Physiology School of MedicineShanghai Jiao Tong UniversityShanghaiChina Creative Biosciences(Guangzhou)Co. Ltd.GuangzhouGuangdongChina Department of Colorectal Surgery Guangdong Institute of GastroenterologyGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesThe Sixth Affiliated HospitalSun Yat-Sen UniversityGuangdongChina Shanghai Institute of immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghaiChina

Keloids are an abnormal fibroproliferative wound-healing disease with a poorly understood pathogenesis,making it difficult to predict and prevent this disease in clinical *** 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 *** is mounting evidence of immune cell dysregulation in keloid *** 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 ***-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 *** 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 *** 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 ***,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 ***-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

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