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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

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:36439145
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title
NFIL3 and its immunoregulatory role in rheumatoid arthritis patients.
doi
10.3389/fimmu.2022.950144
pmid
36439145
authors array · 12 items
[0]
Juping Du
[1]
Liyuan Zheng
[2]
Shuaishuai Chen
[3]
Na Wang
[4]
Xia Pu
[5]
Die Yu
[6]
Haixi Yan
[7]
Jiaxi Chen
[8]
Donglian Wang
[9]
Bo Shen
[10]
Jun Li
[11]
Shaobiao Pan
journal
Frontiers in immunology
year
2022
abstract
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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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).
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sections[5] "Analysis of NFIL3 expression in rheumatoid arthritis synovial tissues in the gene expression omnibus database" paragraph 2
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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).
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sections[15] "Data availability statement" paragraph 2
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The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.
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A total of 405 genes were significantly differentially expressed between the NFIL3-high and NFIL3-low rheumatoid arthritis synovial tissue groups.
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sections[10] "Identification of differentially expressed genes in different NFIL3 subgroups" paragraph 2
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A total of 405 genes (upregulated, 191; downregulated, 214) showed significant differential expression between these two groups ( Table S4 ).
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A total of 405 genes were significantly differentially expressed between the NFIL3-high and NFIL3-low rheumatoid arthritis synovial tissue groups.
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RNAseq study of synovial biopsies
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nd 75 healthy controls (HCs) by quantitative real-time PCR (qRT-PCR). No correlation between NFIL3 and
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36439145", "kind": "science-record", "revision": 4, "content_hash": "sha256:daf0f016f2f69afcbb5c665d28f78d9f89a4161ecf4242462a8b08d5e64592a5", "created_at": "2026-11-01T19:00:55Z", "updated_at": "2026-11-01T22:50:42Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "NFIL3 and its immunoregulatory role in rheumatoid arthritis patients.", "doi": "10.3389/fimmu.2022.950144", "pmid": "36439145", "authors": ["Juping Du", "Liyuan Zheng", "Shuaishuai Chen", "Na Wang", "Xia Pu", "Die Yu", "Haixi Yan", "Jiaxi Chen", "Donglian Wang", "Bo Shen", "Jun Li", "Shaobiao Pan"], "journal": "Frontiers in immunology", "year": 2022, "abstract": "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.", "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. Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36439145", "locator": "sections[15] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 405 genes were significantly differentially expressed between the NFIL3-high and NFIL3-low rheumatoid arthritis synovial tissue groups.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36439145", "locator": "sections[10] \"Identification of differentially expressed genes in different NFIL3 subgroups\" paragraph 2", "quote": "A total of 405 genes (upregulated, 191; downregulated, 214) showed significant differential expression between these two groups ( Table S4 )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 405 genes were significantly differentially expressed between the NFIL3-high and NFIL3-low rheumatoid arthritis synovial tissue groups.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36439145"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE89408"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE89408"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36439145", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2022.950144", "sha256": "sha256:2f577c470f0fc1e879e2d2c9cbfc12290d48270471ab3b698357f57899d2800e", "bytes": 44319, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2022.950144", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9692021", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE89408", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89408", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE89408", "version": null, "note": "The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2370970", "GSM2370971", "GSM2370972", "GSM2370973", "GSM2370974", "GSM2370975", "GSM2370976", "GSM2370977", "GSM2370978", "GSM2370979", "GSM2370980", "GSM2370981", "GSM2370982", "GSM2370983", "GSM2370984", "GSM2370985", "GSM2370986", "GSM2370987", "GSM2370988", "GSM2370989", "GSM2370990", "GSM2370991", "GSM2370992", "GSM2370993", "GSM2370994", "GSM2370995", "GSM2370996", "GSM2370997", "GSM2370998", "GSM2370999", "GSM2371000", "GSM2371001", "GSM2371002", "GSM2371003", "GSM2371004", "GSM2371005", "GSM2371006", "GSM2371007", "GSM2371008", "GSM2371009", "GSM2371010", "GSM2371011", "GSM2371012", "GSM2371013", "GSM2371014", "GSM2371015", "GSM2371016", "GSM2371017", "GSM2371018", "GSM2371019", "GSM2371020", "GSM2371021", "GSM2371022", "GSM2371023", "GSM2371024", "GSM2371025", "GSM2371026", "GSM2371027", "GSM2371028", "GSM2371029", "GSM2371030", 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE89408"], "resolved_accessions": ["GSE89408"], "statements": ["The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors."], "basis": "The paper names GSE89408 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:36439145", "data:geo:GSE89408"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE89408"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:17:09Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13107, "completion_tokens": 913, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:36439145", "type": "paper", "label": "pmid:36439145"}, {"id": "source:pmid:36439145", "type": "manuscript", "label": "PMID 36439145 full text"}, {"id": "data:geo:GSE89408", "type": "dataset", "label": "GEO GSE89408"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36439145", "type": "paper", "label": "pmid:36439145"}, {"id": "source:pmid:36439145", "type": "manuscript", "label": "PMID 36439145 full text"}, {"id": "data:geo:GSE89408", "type": "dataset", "label": "GEO GSE89408"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36439145", "type": "extraction", "used": ["source:pmid:36439145"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE89408", "type": "accession_resolution", "used": ["data:geo:GSE89408"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:36439145", "parent_hash": "sha256:5cd5504d6f7d7d162a5cf77c6367ea0e3243662118bc6e3cb6352e2a87311f48", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE89408 licence not read", "asset:data:geo:GSE89408 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["nd 75 healthy controls (HCs) by quantitative real-time PCR (qRT-PCR). No correlation between NFIL3 and"], "order_basis": "paper_text_order:531", "id": "assay:1"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["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)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}