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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...

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Autores principales: Du, Juping, Zheng, Liyuan, Chen, Shuaishuai, Wang, Na, Pu, Xia, Yu, Die, Yan, Haixi, Chen, Jiaxi, Wang, Donglian, Shen, Bo, Li, Jun, Pan, Shaobiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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.
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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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