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pmid:36439145
NFIL3 and its immunoregulatory role in rheumatoid arthritis patients.
Juping Du · Liyuan Zheng · Shuaishuai Chen · Na Wang · Xia Pu · Die Yu · Haixi Yan · Jiaxi Chen · Donglian Wang · Bo Shen · Jun Li · Shaobiao Pan
Frontiers in immunology · 2022 doi:10.3389/fimmu.2022.950144
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Complete file
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However, the relationship between rheumatoid arthritis (RA) and NFIL3 remains largely unknown. In this study, we examined NFIL3 expression in RA patients and its potential molecular mechanisms in RA. Increased NFIL3 expression levels were identified in peripheral blood mononuclear cells (PBMCs) from 62 initially diagnosed RA patients and 75 healthy controls (HCs) by quantitative real-time PCR (qRT-PCR). No correlation between NFIL3 and disease activity was observed. In addition, NFIL3 expression was significantly upregulated in RA synovial tissues analyzed in the Gene Expression Omnibus (GEO) dataset (GSE89408). Then, we classified synovial tissues into NFIL3-high (≥75%) and NFIL3-low (≤25%) groups according to NFIL3 expression levels. Four hundred five differentially expressed genes (DEGs) between the NFIL3-high and NFIL3-low groups were screened out using the \"limma\" R package. Enrichment analysis showed that most of the enriched genes were primarily involved in the TNF signaling pathway via NFκB, IL-17 signaling pathway, and rheumatoid arthritis pathways. Then, 10 genes (IL6, IL1β, CXCL8, CCL2, PTGS2, MMP3, MMP1, FOS, SPP1, and ADIPOQ) were identified as hub genes, and most of them play a key role in RA. Positive correlations between the hub genes and NFIL3 were revealed by qRT-PCR in RA PBMCs. An NFIL3-related protein-protein interaction (PPI) network was constructed using the STRING database, and four clusters (mainly participating in the inflammatory response, lipid metabolism process, extracellular matrix organization, and circadian rhythm) were constructed with MCODE in Cytoscape. Furthermore, 29 DEGs overlapped with RA-related genes from the RADB database and were mainly enriched in IL-17 signaling pathways. Thus, our study revealed the elevated expression of NFIL3 in both RA peripheral blood and synovial tissues, and the high expression of NFIL3 correlated with the abnormal inflammatory cytokines and inflammatory responses, which potentially contributed to RA progression.", "claims": [{"id": "claim-method", "statement": "Differential expression analysis between the RA and HC groups and between the NFIL3-high and NFIL3-low groups was conducted using the limma package of R language (version 4.1.2).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36439145", "locator": "sections[5] \"Analysis of NFIL3 expression in rheumatoid arthritis synovial tissues in the gene expression omnibus database\" paragraph 2", "quote": "Differential expression analysis between the RA and HC groups and between the NFIL3-high and NFIL3-low groups was conducted using the limma package of R language (version 4.1.2)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/supplementary material. 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