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NFIL3 and its immunoregulatory role in rheumatoid arthritis patients
Nuclear-factor, interleukin 3 regulated (NFIL3) is an immune regulator that plays an essential role in autoimmune diseases. 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 mole...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692021/ https://www.ncbi.nlm.nih.gov/pubmed/36439145 http://dx.doi.org/10.3389/fimmu.2022.950144 |
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author | Du, Juping Zheng, Liyuan Chen, Shuaishuai Wang, Na Pu, Xia Yu, Die Yan, Haixi Chen, Jiaxi Wang, Donglian Shen, Bo Li, Jun Pan, Shaobiao |
author_facet | Du, Juping Zheng, Liyuan Chen, Shuaishuai Wang, Na Pu, Xia Yu, Die Yan, Haixi Chen, Jiaxi Wang, Donglian Shen, Bo Li, Jun Pan, Shaobiao |
author_sort | Du, Juping |
collection | PubMed |
description | Nuclear-factor, interleukin 3 regulated (NFIL3) is an immune regulator that plays an essential role in autoimmune diseases. 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. |
format | Online Article Text |
id | pubmed-9692021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96920212022-11-26 NFIL3 and its immunoregulatory role in rheumatoid arthritis patients Du, Juping Zheng, Liyuan Chen, Shuaishuai Wang, Na Pu, Xia Yu, Die Yan, Haixi Chen, Jiaxi Wang, Donglian Shen, Bo Li, Jun Pan, Shaobiao Front Immunol Immunology Nuclear-factor, interleukin 3 regulated (NFIL3) is an immune regulator that plays an essential role in autoimmune diseases. 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. Frontiers Media S.A. 2022-11-11 /pmc/articles/PMC9692021/ /pubmed/36439145 http://dx.doi.org/10.3389/fimmu.2022.950144 Text en Copyright © 2022 Du, Zheng, Chen, Wang, Pu, Yu, Yan, Chen, Wang, Shen, Li and Pan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Du, Juping Zheng, Liyuan Chen, Shuaishuai Wang, Na Pu, Xia Yu, Die Yan, Haixi Chen, Jiaxi Wang, Donglian Shen, Bo Li, Jun Pan, Shaobiao NFIL3 and its immunoregulatory role in rheumatoid arthritis patients |
title | NFIL3 and its immunoregulatory role in rheumatoid arthritis patients |
title_full | NFIL3 and its immunoregulatory role in rheumatoid arthritis patients |
title_fullStr | NFIL3 and its immunoregulatory role in rheumatoid arthritis patients |
title_full_unstemmed | NFIL3 and its immunoregulatory role in rheumatoid arthritis patients |
title_short | NFIL3 and its immunoregulatory role in rheumatoid arthritis patients |
title_sort | nfil3 and its immunoregulatory role in rheumatoid arthritis patients |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692021/ https://www.ncbi.nlm.nih.gov/pubmed/36439145 http://dx.doi.org/10.3389/fimmu.2022.950144 |
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