IκB Kinase-β Regulates Neutrophil Recruitment Through Activation of STAT3 Signaling in the Esophagus.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34311141", "kind": "science-record", "revision": 8, "content_hash": "sha256:7d549c2809d21546affc6ec2b9f8fa8908d769a1f4daee6417ecdcb511225f77", "created_at": "2026-11-01T15:41:45Z", "updated_at": "2026-11-01T22:47:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "IκB Kinase-β Regulates Neutrophil Recruitment Through Activation of STAT3 Signaling in the Esophagus.", "doi": "10.1016/j.jcmgh.2021.07.007", "pmid": "34311141", "authors": ["Kelsey Nicole Wiles", "Cara Maria Alioto", "Nathan Bruce Hodge", "Margarette Helen Clevenger", "Lia Elyse Tsikretsis", "Frederick T J Lin", "Marie-Pier Tétreault"], "journal": "Cellular and molecular gastroenterology and hepatology", "year": 2021, "abstract": "BACKGROUND & AIMS: The epithelial barrier is the host's first line of defense against damage to the underlying tissue. Upon injury, the epithelium plays a critical role in inflammation. The IκB kinase β (IKKβ)/nuclear factor-κB pathway was shown to be active in the esophageal epithelium of patients with esophageal disease. However, the complex mechanisms by which IKKβ signaling regulates esophageal disease pathogenesis remain unknown. Our prior work has shown that expression of a constitutively active form of IKKβ specifically in esophageal epithelia of mice (IkkβcaEsophageal Epithelial Cell-Knockin (EEC-KI)) is sufficient to cause esophagitis.\nMETHODS: We generated ED-L2/Cre;Rosa26-Ikkβca+/L;Stat3L/L (IkkβcaEEC-KI;Stat3Esophageal Epithelial Cell Knockout (EEC-KO)) mice, in which the ED-L2 promoter activates Cre recombinase in the esophageal epithelium, leading to constitutive activation of IKKβ and loss of Stat3. Esophageal epithelial tissues were collected and analyzed by immunostaining, RNA sequencing, quantitative real-time polymerase chain reaction assays, flow cytometry, and Western blot. IkkβcaEEC-KI mice were treated with neutralizing antibodies against interleukin (IL)23p19 and IL12p40.\nRESULTS: Here, we report that IkkβcaEEC-KI mice have increased activation of epithelial Janus kinase 2/STAT3 signaling. Stat3 deletion in IkkβcaEEC-KI mice attenuated the neutrophil infiltration observed in IkkβcaEEC-KI mice and resulted in decreased expression of genes related to immune cell recruitment and activity. Blocking experiments in IkkβcaEEC-KI mice showed that STAT3 activation and subsequent neutrophil recruitment are dependent on IL23 secretion.\nCONCLUSIONS: Our study establishes a novel interplay between IKKβ and STAT3 signaling in epithelial cells of the esophagus, where IKKβ/IL23/STAT3 signaling controls neutrophil recruitment during the onset of inflammation. GEO accession number: GSE154129.", "claims": [{"id": "claim-data-access", "statement": "RNA sequencing was deposited in Gene Expression Omnibus (GSE154129) and can be accessed at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154129.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34311141", "locator": "sections[17] \"RNA Sequencing\" paragraph 2", "quote": "RNA sequencing was deposited in Gene Expression Omnibus (GSE154129) and can be accessed at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154129."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:34311141"], "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:GSE154129"], "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:GSE154129"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34311141", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.jcmgh.2021.07.007", "sha256": "sha256:f24b01c9a8c5928cfcda3f600670e76bfb24cead9c0008c22234974c41c7df85", "bytes": 69818, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.jcmgh.2021.07.007", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8551782", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE154129", "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=GSE154129", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE154129", "version": null, "note": "RNA sequencing was deposited in Gene Expression Omnibus (GSE154129) and can be accessed at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154129.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "RNA sequencing was deposited in Gene Expression Omnibus (GSE154129) and can be accessed at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154129.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4664339", "GSM4664340", "GSM4664341", "GSM4664342", "GSM4664343", "GSM4664344", "GSM4664345", "GSM4664346", "GSM4664347", "GSM4664348", "GSM4664349", "GSM4664350"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "21103", "taxon": "Mus musculus", "title": "Overexpression of constitutively active Ikkb and/or loss of Stat3 in murine esophageal epithelium", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:34311141:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f8b5b18c0ce6322f3b4e3f26bfdaaee71ee04b3b46feb8b4a25985cd2d5733d8", "bytes": 1176, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#tbl1", "version": null, "note": "Antibodies for Flow Cytometry", "structure": {"pmcid": "PMC8551782", "section_index": 18, "section_title": "Flow Cytometry", "row_count": 19, "column_count": 5}, "table": {"label": "Table 1", "caption": "Antibodies for Flow Cytometry", "rows": [["Antibody", "Clone", "Fluorophore", "Company", "Catalog number"], ["CD115", "T38-320", "BV421", "BD Biosciences", "743638"], ["CD117", "2B8", "BV711", "BD Biosciences", "563160"], ["CD11b", "M1/70", "BUV737", "BD Biosciences", "564443"], ["CD11c", "HL3", "BUV395", "BD Biosciences", "564080"], ["CD170", "E50-2440", "PE-CF594", "BD Biosciences", "562757"], ["CD19", "1D3", "APC-Cy7", "BD Biosciences", "557655"], ["CD31", "390", "AF488", "BD Biosciences", "563607"], ["CD3e", "500A2", "AF700", "BD Biosciences", "557984"], ["CD4", "GK1.5", "BUV496", "BD Biosciences", "564667"], ["CD44", "1M7", "BV786", "BD Biosciences", "563736"], ["CD45.2", "104", "BV650", "BD Biosciences", "740490"], ["CD49b", "Hma2", "BV605", "BD Biosciences", "740363"], ["CD8a", "53-6.7", "BB700", "BD Biosciences", "566409"], ["F4/80", "T45-2342", "A647", "BD Biosciences", "565854"], ["FoxP3", "FJK-16s", "PE", "eBioscience", "12-5773-80"], ["Live/Dead", "N/A", "506e", "eBioscience", "65-0866-14"], ["Ly6G", "1A8", "PE-Cy7", "BD Biosciences", "560601"], ["NK 1.1", "PK136", "BB630", "BD Biosciences", "624294"]], "row_count": 19, "column_count": 5, "numeric_cells": 60, "header_rows": 1, "locator": "section[18]/table-wrap[1]#tbl1"}}], "gaps": ["asset:data:geo:GSE154129 not downloaded", "asset:data:geo:GSE154129 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "deseq2", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "reordered", "quote": "“Normalization and differential expression were determined using DESeq2.” “RNA sequencing was deposited in Gene Expression Omnibus (GSE154129) and can be accessed at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154129.”"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: deseq2."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE154129"], "resolved_accessions": ["GSE154129"], "statements": ["RNA sequencing was deposited in Gene Expression Omnibus (GSE154129) and can be accessed at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154129."], "basis": "The paper names GSE154129 in Gene Expression Omnibus (GEO) 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:34311141", "data:geo:GSE154129", "asset:table:pmid:34311141:1"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE154129"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:32:49Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 57465, "completion_tokens": 874, "cached_tokens": 776}}, "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:34311141", "type": "paper", "label": "pmid:34311141"}, {"id": "source:pmid:34311141", "type": "manuscript", "label": "PMID 34311141 full text"}, {"id": "data:geo:GSE154129", "type": "dataset", "label": "GEO GSE154129"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34311141", "type": "paper", "label": "pmid:34311141"}, {"id": "source:pmid:34311141", "type": "manuscript", "label": "PMID 34311141 full text"}, {"id": "data:geo:GSE154129", "type": "dataset", "label": "GEO GSE154129"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34311141", "type": "extraction", "used": ["source:pmid:34311141"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE154129", "type": "accession_resolution", "used": ["data:geo:GSE154129"], "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:34311141", "parent_hash": "sha256:7701a70e463bb813b71d7814c194273bb2555a6c2aba692109a91d4983db3280", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE154129 licence not read", "asset:data:geo:GSE154129 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["elial tissues were collected and analyzed by immunostaining, RNA sequencing, quantitative real-time poly"], "order_basis": "paper_text_order:1046", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["re collected and analyzed by immunostaining, RNA sequencing, quantitative real-time polymerase chain rea"], "order_basis": "paper_text_order:1062", "id": "assay:2"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["real-time polymerase chain reaction assays, flow cytometry, and Western blot. IkkβcaEEC-KI mice were tr"], "order_basis": "paper_text_order:1136", "id": "assay:3"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["e chain reaction assays, flow cytometry, and Western blot. IkkβcaEEC-KI mice were treated with neutral"], "order_basis": "paper_text_order:1155", "id": "assay:4"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ow cytometry, and Western blot. IkkβcaEEC-KI mice were treated with neutralizing antibodies against"], "order_basis": "paper_text_order:1182", "id": "assay:5"}, {"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": ["“Normalization and differential expression were determined using DESeq2.” “RNA sequencing was deposited in Gene Expression Omnibus (GSE154129) and can be accessed at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154129.”"], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}