Plasma-derived exosomal protein SHP2 deficiency induces neutrophil hyperactivation in Behcet's uveitis
作者全名："Cai, Jinyu; Wang, Qingfeng; Tan, Shiyao; Jiang, Qingyan; Liu, Rong; Su, Guannan; Yi, Shenglan; Yang, Peizeng"
作者地址："[Cai, Jinyu; Wang, Qingfeng; Tan, Shiyao; Jiang, Qingyan; Liu, Rong; Su, Guannan; Yi, Shenglan; Yang, Peizeng] Chongqing Med Univ, Chongqing Eye Inst, Natl Clin Res Ctr Ocular Dis, Chongqing Key Lab Ophthalmol,Affiliated Hosp 1,Cho, Chongqing, Peoples R China"
通信作者："Yang, PZ (通讯作者)，Chongqing Med Univ, Chongqing Eye Inst, Natl Clin Res Ctr Ocular Dis, Chongqing Key Lab Ophthalmol,Affiliated Hosp 1,Cho, Chongqing, Peoples R China."
来源：EXPERIMENTAL EYE RESEARCH
ESI学科分类：CLINICAL MEDICINE
WOS号：WOS:001170821800001
JCR分区：Q1
影响因子：3
年份：2024
卷号：239
期号：
开始页：
结束页：
文献类型：Article
关键词：Behcet 's uveitis; Exosomal protein; SHP2; Neutrophil hyperactivation
摘要："To investigate the effect of plasma-derived exosomal proteins on neutrophil hyperactivation in Behcet's uveitis (BU), we treated neutrophils from healthy controls with plasma-derived exosomes from active BU patients, and determined the level of neutrophil activation by real-time quantitative PCR (RT-qPCR) and cytokine detection assay. The results revealed that exosomes from active BU patients could activate neutrophils as shown by increasing the expression levels of pro-inflammatory cytokines (IL-17 and IL-6), chemokines (IL-8 and MCP-1), and NETs (MPO and ELANE). Label-free quantitative proteomic analysis of plasma-derived exosomes from patients and healthy controls found a remarkably distinct protein profile and identified differentially expressed proteins (DEPs) between the two groups. The results of GO, KEGG, and GSEA enrichment analysis showed that DEPs were enriched in innate immune-mediated and neutrophil hyperactivation-related signaling pathways. The protein-protein interaction (PPI) analysis determined that SHP2 was a downregulated key hub protein in the exosomes of active BU patients. Knockdown of SHP2 in human neutrophil cell lines (NB4 cells) was shown to promote the secretion of pro-inflammatory cytokines, chemokines, and NETs. The converse effects were observed following SHP2 overexpression. In conclusion, we highlighted a pathogenic role of plasma-derived exosomal SHP2 deficiency in facilitating neutrophil activation and suggested that SHP2 might be an immunoprotective factor in BU pathologic process."
基金机构："National Natural Science Foundation Key Program [cstc2021jcyj-bshX0154, 81930023]; Key Project of Chongqing Science and Technology Bureau [CSTC2021jscx-gksb-N0010]; National Natural Science Foundation [82101106, 82000884]; Chongqing Outstanding Scientists Projct (2019); Natural Science Foundation of Chongqing; Chongqing Key Laboratory of Ophthalmology (CSTC) [cstc2014pt-sy10002]; Chongqing Science & Technology Platform and Base Construction Program [82230032]; [2008CA5003]"
基金资助正文："This work was supported by the National Natural Science Foundation Key Program (82230032) , National Natural Science Foundation Key Program (81930023) , Key Project of Chongqing Science and Technology Bureau (CSTC2021jscx-gksb-N0010) , National Natural Science Foundation (82101106, 82000884) , Chongqing Outstanding Scientists Projct (2019) , Natural Science Foundation of Chongqing (cstc2021jcyj-bshX0154) , Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003) , and the Chongqing Science & Technology Platform and Base Construction Program (cstc2014pt-sy10002) ."
