Identification of SLAMF1 as an immune-related key gene associated with rheumatoid arthritis and verified in mice collagen-induced arthritis model.
Identification of SLAMF1 as an immune-related key gene associated with rheumatoid arthritis and verified in mice collagen-induced arthritis model.
复制标题
鉴定SLAMF1为与类风湿性关节炎相关的免疫相关关键基因，并在小鼠胶原诱导的关节炎模型中得到验证
DOI：
10.3389/fimmu.2022.961129
复制
发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
类风湿关节炎（RA）是最常见的炎性关节病。免疫失调与RA的发病机制有关。因此，本研究的目的是确定RA中的免疫相关生物标志物。
我们从基因表达综合数据库（GEO）下载了GSE89408和GSE45291中RA的基因表达数据。在RA组和对照组之间鉴定出差异表达基因（DEGs）。通过单样本基因集富集分析（ssGSEA）和加权基因共表达网络分析（WGCNA）获得浸润免疫细胞相关基因。我们通过“clusterProfiler”R包对差异表达的免疫相关基因（DEIRGs）进行功能富集分析，通过DEIRGs的蛋白质 - 蛋白质相互作用（PPI）网络筛选关键基因。并且采用小鼠胶原诱导性关节炎（CIA）模型来验证这些关键基因。
在RA样本中总共鉴定出1885个上调和1899个下调的DEGs。ssGSEA分析表明25种细胞的浸润存在显著差异。通过WGCNA获得603个免疫相关基因，通过取DEGs和免疫相关基因的交集获得270个DEIRGs。富集分析表明DEIRGs与免疫相关的生物学过程有关。从DEIRGs的PPI网络和文献研究中鉴定出4个候选生物标志物（CCR7、KLRK1、TIGIT和SLAMF1）。
在小鼠CIA模型中，免疫组化染色显示SLAMF1在患病关节中具有显著高表达。并且流式细胞术分析表明，CIA小鼠来源的细胞毒性T淋巴细胞（CTL）、辅助性T细胞（Th）、自然杀伤细胞（NK）、自然杀伤T细胞（NKT）、经典树突状细胞（cDCs）和单核细胞/巨噬细胞上SLAMF1的表达也显著高于来自健康对照（HC）小鼠的相应免疫细胞。
我们的研究确定SLAMF1是RA发生和发展中的一个关键生物标志物，这可能为探索RA的发病机制提供新的见解。
Rheumatoid arthritis (RA) is the most common inflammatory arthropathy. Immune dysregulation was implicated in the pathogenesis of RA. Thus, the aim of the research was to determine the immune related biomarkers in RA. We downloaded the gene expression data of RA in GSE89408 and GSE45291 from Gene Expression Omnibus public database (GEO). Differentially expressed genes (DEGs) were identified between RA and control groups. Infiltrating immune cells related genes were obtained by ssGSEA and weighted gene co-expression network analysis (WGCNA). We performed functional enrichment analysis of differentially expressed immunity-related genes (DEIRGs) by “clusterProfiler” R package, key genes screening by protein-protein interaction (PPI) network of DEIRGs. And mice collagen-induced arthritis (CIA) model was employed to verify these key genes. A total of 1,885 up-regulated and 1,899 down-regulated DEGs were identified in RA samples. The ssGSEA analysis showed that the infiltration of 25 cells was significantly different. 603 immune related genes were obtained by WGCNA, and 270 DEIRGs were obtained by taking the intersection of DEGs and immune related genes. Enrichment analyses indicated that DEIRGs were associated with immunity related biological processes. 4 candidate biomarkers (CCR7, KLRK1, TIGIT and SLAMF1) were identified from the PPI network of DEIRGs and literature research. In mice CIA model, the immunohistochemical stain showed SLAMF1 has a significantly high expression in diseased joints. And flow cytometry analysis shows the expression of SLAMF1 on CIA mice-derived CTL cells, Th, NK cells, NKT cells, classical dendritic cell (cDCs) and monocytes/macrophages was also significantly higher than corresponding immune cells from HC mice. Our study identified SMLAF1 as a key biomarker in the development and progression of RA, which might provide new insight for exploring the pathogenesis of RA.
登录
查看更多内容
影响因子：
5.5
作者：
Conti V;Corbi G;Costantino M;De Bellis E;Manzo V;Sellitto C;Stefanelli B;Colucci F;Filippelli A
通讯作者：
Filippelli A
DOI：
10.18632/aging.203641
发表时间：
2021-10-20
期刊：
Aging
影响因子：
--
作者：
Chen Y;Ma C;Liu L;He J;Zhu C;Zheng F;Dai W;Hong X;Liu D;Tang D;Dai Y
通讯作者：
Dai Y
影响因子：
30.5
作者：
Weyand CM;Goronzy JJ
通讯作者：
Goronzy JJ
影响因子：
2.1
作者：
Tenstad, H. B.;Nilsson, A. C.;Lillevang, S. T.
通讯作者：
Lillevang, S. T.
影响因子：
6
作者：
Yap HY;Tee SZ;Wong MM;Chow SK;Peh SC;Teow SY
通讯作者：
Teow SY