Identification of SLAMF1 as an immune-related key gene associated with rheumatoid arthritis and verified in mice collagen-induced arthritis model

Copyright © 2022 Li, Zhang, Ru, Yi, Li, Qian, Wang, Yang and Yao..

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Frontiers in immunology - 13(2022) vom: 08., Seite 961129

Sprache:

Englisch

Beteiligte Personen:

Li, Anqi [VerfasserIn]
Zhang, Zhanfeng [VerfasserIn]
Ru, Xiaochen [VerfasserIn]
Yi, Yanfeng [VerfasserIn]
Li, Xiaoyu [VerfasserIn]
Qian, Jing [VerfasserIn]
Wang, Jue [VerfasserIn]
Yang, Xiaobing [VerfasserIn]
Yao, Yunliang [VerfasserIn]

Links:

Volltext

Themen:

169535-43-7
Animal model
Bioinformatics
Biomarkers
Collagen-induced arthritis
Journal Article
Key gene
Klrk1 protein, mouse
NK Cell Lectin-Like Receptor Subfamily K
Receptors, CCR7
Rheumatoid arthritis
SLAMF1
SLAMF1 protein, human
Signaling Lymphocytic Activation Molecule Family Member 1
Slamf1 protein, mouse

Anmerkungen:

Date Completed 19.09.2022

Date Revised 28.09.2022

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.3389/fimmu.2022.961129

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM346275997