{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:23:47Z","timestamp":1787739827285,"version":"build-2784847793"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011019","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["2023-1.1.1-PIACI_F\u00d3KUSZ-2024\u201300036"],"award-info":[{"award-number":["2023-1.1.1-PIACI_F\u00d3KUSZ-2024\u201300036"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["K145994"],"award-info":[{"award-number":["K145994"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["EXCELLENCE_151396"],"award-info":[{"award-number":["EXCELLENCE_151396"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["ADVANCED_152995"],"award-info":[{"award-number":["ADVANCED_152995"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["2024\/5S811 SZTE SZAOK-KKA"],"award-info":[{"award-number":["2024\/5S811 SZTE SZAOK-KKA"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["BO\/00594\/22\/8"],"award-info":[{"award-number":["BO\/00594\/22\/8"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["LP2022-4\/2022a"],"award-info":[{"award-number":["LP2022-4\/2022a"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hungarian National Research, Development, and Innovation Office","award":["142877 FK22"],"award-info":[{"award-number":["142877 FK22"]}]},{"name":"University Research Scholarship Program \u2013 Cooperative Doctoral Program"},{"name":"Hungarian National Research, Development and Innovation Office","award":["EK\u00d6P-KDP-2\/2025"],"award-info":[{"award-number":["EK\u00d6P-KDP-2\/2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>IFN\u03b3 and IL-4, the canonical Th1 and Th2 cytokines, typically induce opposing macrophage polarization. Beyond their frequent coexistence and mutual antagonism in pathological settings, a synergistic crosstalk may also exist and remains to be defined. Through integrated transcriptomic, epigenomic, and CRISPR-based analyses, we identify that co-exposure to IL-4 and IFN\u03b3 results in an intermediate macrophage polarization state in murine macrophages, associated with a cohort of synergistically activated genes. We show that this synergistic activation is mediated by co-binding of STAT6 and STAT1 at regulatory regions marked with pronounced H3K27Ac accumulation and is dependent on the BRD4 cofactor. Deletion of either STAT factor or disruption of their binding motifs abolishes the synergistic transcriptional response. Our data support a model in which chromatin openness induced by one cytokine facilitates binding of the opposing cytokine-activated STAT transcription factor (TF), contributing to synergistic gene activation. We further show that IRF1, an IFN\u03b3-induced TF whose expression persists in the presence of IL-4, is indispensable for a substantial subset of this program. Importantly, single-cell RNA sequencing of the PyMT murine breast cancer model reveals an in vivo tumor-associated macrophage subset showing STAT1 and STAT6 activation and is enriched for the synergistic gene signature.<\/jats:p>","DOI":"10.1093\/nar\/gkag825","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:58:43Z","timestamp":1787738323000},"source":"Crossref","is-referenced-by-count":0,"title":["Synergistic interaction between the macrophage polarizing signals IL-4 and IFN\u03b3 is controlled by the STAT6\/STAT1\/IRF1 axis"],"prefix":"10.1093","volume":"54","author":[{"given":"Zs\u00f3fia","family":"Varga","sequence":"first","affiliation":[{"name":"Institute of Genetics, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Poscher","sequence":"additional","affiliation":[{"name":"Institute of Genetics, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]},{"name":"Doctoral School in Biology, University of Szeged , Szeged, H-6726 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter Anna","family":"V\u00e1radi","sequence":"additional","affiliation":[{"name":"Institute of Genetics, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]},{"name":"Doctoral School in Biology, University of Szeged , Szeged, H-6726 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6ngyi","family":"Cinege","sequence":"additional","affiliation":[{"name":"Institute of Genetics, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antal","family":"Izs\u00e1n","sequence":"additional","affiliation":[{"name":"Institute of Genetics, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7223-0946","authenticated-orcid":false,"given":"Edina","family":"Erd\u0151s","sequence":"additional","affiliation":[{"name":"Institute of Genetics, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadett","family":"Benyhe-Kis","sequence":"additional","affiliation":[{"name":"Institute of Genetics, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]},{"name":"Doctoral School in Biology, University of Szeged , Szeged, H-6726 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Zsuzsanna","family":"Tihanyi","sequence":"additional","affiliation":[{"name":"Institute of Genetics, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]},{"name":"Doctoral School in Biology, University of Szeged , Szeged, H-6726 ,","place":["Hungary"]},{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petros","family":"Tzerpos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen , Debrecen, H-4032 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriszti\u00e1n","family":"Bene","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen , Debrecen, H-4032 ,","place":["Hungary"]},{"name":"Institute for Fundamental Biomedical Research, Johns Hopkins All Children\u2019s Hospital , St. Petersburg, FL 33701 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Hal\u00e1sz","sequence":"additional","affiliation":[{"name":"Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["United States"]},{"name":"Department of Medicine and Biomedical Engineering, Johns Hopkins University School of Medicine , Baltimore, MD 21205 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolett","family":"G\u00e9mes","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Neuperger","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rta","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Division of Allergy\/Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida , Tampa, FL 33620 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8312-6463","authenticated-orcid":false,"given":"Ede","family":"Migh","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szil\u00e1rd","family":"P\u00f3liska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen , Debrecen, H-4032 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor J","family":"Szebeni","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]},{"name":"Department of Internal Medicine, Hematology Centre, Faculty of Medicine, University of Szeged , Szeged, H-6725 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jol\u00e1n E","family":"Walter","sequence":"additional","affiliation":[{"name":"Division of Allergy\/Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida , Tampa, FL 33620 ,","place":["United States"]},{"name":"Department of Pediatrics, Johns Hopkins All Children Hospital , St. Petersburg, FL 33701 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bence","family":"D\u00e1niel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University , Stanford, CA 94305 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1lint","family":"Cs\u00f6rg\u0151","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen , Debrecen, H-4032 ,","place":["Hungary"]},{"name":"Institute for Fundamental Biomedical Research, Johns Hopkins All Children\u2019s Hospital , St. Petersburg, FL 33701 ,","place":["United States"]},{"name":"Department of Medicine and Biomedical Engineering, Johns Hopkins University School of Medicine , Baltimore, MD 21205 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3407-5006","authenticated-orcid":false,"given":"Zsolt","family":"Czimmerer","sequence":"additional","affiliation":[{"name":"Institute of Genetics, HUN-REN Biological Research Centre , Szeged, H-6726 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"2026082605583600100_B1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/ni.3341","article-title":"The development and maintenance of resident macrophages","volume":"17","author":"Perdiguero","year":"2016","journal-title":"Nat Immunol"},{"key":"2026082605583600100_B2","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1146\/annurev-physiol-022516-034339","article-title":"Macrophage polarization","volume":"79","author":"Murray","year":"2017","journal-title":"Annu Rev Physiol"},{"key":"2026082605583600100_B3","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.immuni.2014.06.008","article-title":"Macrophage activation and polarization: nomenclature and experimental guidelines","volume":"41","author":"Murray","year":"2014","journal-title":"Immunity"},{"key":"2026082605583600100_B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/8148272","article-title":"Regulating the polarization of macrophages: a promising approach to vascular dermatosis","volume":"8148272","author":"Peng","year":"2020","journal-title":"J Immunol Res"},{"key":"2026082605583600100_B5","doi-asserted-by":"publisher","first-page":"520","DOI":"10.7150\/ijbs.8879","article-title":"Macrophage polarization in inflammatory diseases","volume":"10","author":"Liu","year":"2014","journal-title":"Int J Biol Sci"},{"key":"2026082605583600100_B6","doi-asserted-by":"publisher","first-page":"4111","DOI":"10.1007\/s00018-015-1995-y","article-title":"Macrophage polarization in pathology","volume-title":"Cell Mol Life Sci","author":"Sica","year":"2015"},{"key":"2026082605583600100_B7","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/ni.3306","article-title":"Molecular control of activation and priming in macrophages","volume":"17","author":"Glass","year":"2016","journal-title":"Nat Immunol"},{"key":"2026082605583600100_B8","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1161\/ATVBAHA.113.301453","article-title":"Transcriptional control of macrophage polarization","volume-title":"Arterioscler Thromb Vasc Biol","author":"Tugal","year":"2013"},{"key":"2026082605583600100_B9","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1084\/jem.20151764","article-title":"The macrophage IRF8\/IRF1 regulome is required for protection against infections and is associated with chronic inflammation","volume":"213","author":"Langlais","year":"2016","journal-title":"J Exp Med"},{"key":"2026082605583600100_B10","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/ni.3710","article-title":"Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk","volume":"18","author":"Piccolo","year":"2017","journal-title":"Nat Immunol"},{"key":"2026082605583600100_B11","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1101\/gad.343038.120","article-title":"The transcription factor EGR2 is the molecular linchpin connecting STAT6 activation to the late, stable epigenomic program of alternative macrophage polarization","volume":"34","author":"Daniel","year":"2020","journal-title":"Genes Dev"},{"key":"2026082605583600100_B12","doi-asserted-by":"publisher","first-page":"abf9808","DOI":"10.1126\/sciadv.abf9808","article-title":"Mechanisms underlying divergent responses of genetically distinct macrophages to IL-4","volume":"7","author":"Hoeksema","year":"2021","journal-title":"Sci Adv"},{"key":"2026082605583600100_B13","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1038\/ni.1920","article-title":"The Jmjd3\u2013Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection","volume":"11","author":"Satoh","year":"2010","journal-title":"Nat Immunol"},{"key":"2026082605583600100_B14","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1182\/blood-2011-02-339911","article-title":"Role of c-MYC in alternative activation of human macrophages and tumor-associated macrophage biology","volume":"119","author":"Pello","year":"2012","journal-title":"Blood"},{"key":"2026082605583600100_B15","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.immuni.2018.09.005","article-title":"The nuclear receptor PPAR\u03b3 controls progressive macrophage polarization as a ligand-insensitive epigenomic ratchet of transcriptional memory","volume-title":"Immunity","author":"Daniel","year":"2018"},{"key":"2026082605583600100_B16","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/imm.12623","article-title":"Characteristics of Schistosoma japonicum infection induced IFN- \u03b3 and IL-4 co-expressing plasticity Th cells","volume":"149","author":"Chen","year":"2016","journal-title":"Immunology"},{"key":"2026082605583600100_B17","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.exppara.2006.09.013","article-title":"Leishmania infantum: mixed T-helper-1\/T-helper-2 immune response in experimentally infected BALB\/c mice","volume":"115","author":"Rol\u00e3o","year":"2007","journal-title":"Exp Parasitol"},{"key":"2026082605583600100_B18","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.4161\/hv.22142","article-title":"IL-4 and IFN-\u03b3 induced by human immunodeficiency virus vaccine in a schistosome infection model","volume":"8","author":"Yin","year":"2012","journal-title":"Hum Vaccin Immunother"},{"key":"2026082605583600100_B19","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3390\/cells1020061","article-title":"Increased level of IFN-\u03b3 and IL-4 spot-forming cells on ELISPOT assay as biomarkers for acute graft-versus-host disease and concurrent infections","volume-title":"Cells","author":"Hirayama","year":"2012"},{"key":"2026082605583600100_B20","doi-asserted-by":"publisher","first-page":"1411408","DOI":"10.3389\/fimmu.2024.1411408","article-title":"Altered levels of IFN-\u03b3, IL-4, and IL-5 depend on the TLR4 rs4986790 genotype in COPD smokers but not those exposed to biomass-burning smoke","volume":"15","author":"Gutie\u0301rrez-Romero","year":"2024","journal-title":"Front Immunol"},{"key":"2026082605583600100_B21","doi-asserted-by":"publisher","first-page":"3890","DOI":"10.1177\/0300060518781642","article-title":"Changes in Th1\/Th2-producing cytokines during acute exacerbation chronic obstructive pulmonary disease","volume":"46","author":"Wei","year":"2018","journal-title":"J Int Med Res"},{"key":"2026082605583600100_B22","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.immuni.2017.07.017","article-title":"Interferon-\u03b3 represses M2 gene expression in human macrophages by disassembling enhancers bound by the transcription factor MAF","volume":"47","author":"Kang","year":"2017","journal-title":"Immunity"},{"key":"2026082605583600100_B23","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.molcel.2022.11.017","article-title":"Macrophage inflammatory and regenerative response periodicity is programmed by cell cycle and chromatin state","volume":"83","author":"Daniel","year":"2023","journal-title":"Mol Cell"},{"key":"2026082605583600100_B24","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1016\/j.immuni.2022.10.004","article-title":"The epigenetic state of IL-4-polarized macrophages enables inflammatory cistromic expansion and extended synergistic response to TLR ligands","volume":"55","author":"Czimmerer","year":"2022","journal-title":"Immunity"},{"key":"2026082605583600100_B25","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1101\/gad.242685.114","article-title":"The active enhancer network operated by liganded RXR supports angiogenic activity in macrophages","volume":"28","author":"Daniel","year":"2014","journal-title":"Genes Dev"},{"key":"2026082605583600100_B26","doi-asserted-by":"publisher","first-page":"e168","DOI":"10.1093\/nar\/gku936","article-title":"Easy quantitative assessment of genome editing by sequence trace decomposition","volume":"42","author":"Brinkman","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2026082605583600100_B27","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat Biotechnol"},{"key":"2026082605583600100_B28","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"2026082605583600100_B29","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2026082605583600100_B30","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nbt.3122","article-title":"StringTie enables improved reconstruction of a transcriptome from RNA-seq reads","volume":"33","author":"Pertea","year":"2015","journal-title":"Nat Biotechnol"},{"key":"2026082605583600100_B31","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1038\/nprot.2009.97","article-title":"Mapping identifiers for the integration of genomic datasets with the R\/Bioconductor package biomaRt","volume":"4","author":"Durinck","year":"2009","journal-title":"Nat Protoc"},{"key":"2026082605583600100_B32","doi-asserted-by":"publisher","first-page":"3439","DOI":"10.1093\/bioinformatics\/bti525","article-title":"BioMart and bioconductor: a powerful link between biological databases and microarray data analysis","volume":"21","author":"Durinck","year":"2005","journal-title":"Bioinformatics"},{"key":"2026082605583600100_B33","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal analysis approaches in ingenuity pathway analysis","volume":"30","author":"Kr\u00e4mer","year":"2014","journal-title":"Bioinformatics"},{"key":"2026082605583600100_B34","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows\u2013Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2026082605583600100_B35","doi-asserted-by":"crossref","unstructured":"Danecek P, Bonfield JK, Liddle J \u00a0et al. \u00a0Twelve years of SAMtools and BCFtools. Gigascience. 2021;10:giab008. 10.1093\/gigascience\/giab008.","DOI":"10.1093\/gigascience\/giab008"},{"key":"2026082605583600100_B36","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"2026082605583600100_B37","doi-asserted-by":"publisher","first-page":"W160","DOI":"10.1093\/nar\/gkw257","article-title":"deepTools2: a next generation web server for deep-sequencing data analysis","volume":"44","author":"Ram\u00edrez","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2026082605583600100_B38","doi-asserted-by":"publisher","first-page":"R137","DOI":"10.1186\/gb-2008-9-9-r137","article-title":"Model-based analysis of ChIP-seq (MACS)","volume":"9","author":"Zhang","year":"2008","journal-title":"Genome Biol"},{"key":"2026082605583600100_B39","doi-asserted-by":"publisher","first-page":"vbad104","DOI":"10.1093\/bioadv\/vbad104","article-title":"Cobind: quantitative analysis of the genomic overlaps","volume":"3","author":"Ma","year":"2023","journal-title":"Bioinform Adv"},{"key":"2026082605583600100_B40","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities","volume":"38","author":"Heinz","year":"2010","journal-title":"Mol Cell"},{"key":"2026082605583600100_B41","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1186\/1471-2164-15-284","article-title":"ngs.plot: quick mining and visualization of next-generation sequencing data by integrating genomic databases","volume":"15","author":"Shen","year":"2014","journal-title":"BMC Genomics"},{"key":"2026082605583600100_B42","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat Biotechnol"},{"key":"2026082605583600100_B43","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1093\/bioinformatics\/btab003","article-title":"Nebulosa recovers single-cell gene expression signals by kernel density estimation","volume":"37","author":"Alquicira-Hernandez","year":"2021","journal-title":"Bioinformatics"},{"key":"2026082605583600100_B44","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/j.devcel.2019.05.037","article-title":"Brd4 and P300 confer transcriptional competency during zygotic genome activation","volume":"49","author":"Chan","year":"2019","journal-title":"Dev Cell"},{"key":"2026082605583600100_B45","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1158\/2159-8290.CD-16-0217","article-title":"BRD4 connects enhancer remodeling to senescence immune surveillance","volume":"6","author":"Tasdemir","year":"2016","journal-title":"Cancer Discov"},{"key":"2026082605583600100_B46","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.drudis.2019.11.002","article-title":"Validation of the epigenetic reader bromodomain-containing protein 4 (BRD4) as a therapeutic target for treatment of airway remodeling","volume":"25","author":"Brasier","year":"2020","journal-title":"Drug Discov Today"},{"key":"2026082605583600100_B47","doi-asserted-by":"publisher","first-page":"2166","DOI":"10.1016\/j.molcel.2021.03.008","article-title":"Enhancers are activated by p300\/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release","volume":"81","author":"Narita","year":"2021","journal-title":"Mol Cell"},{"key":"2026082605583600100_B48","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.imbio.2010.05.031","article-title":"Interleukin-4 induced interferon regulatory factor (Irf) 4 participates in the regulation of alternative macrophage priming","volume":"215","author":"El\u00a0Chartouni","year":"2010","journal-title":"Immunobiology"},{"key":"2026082605583600100_B49","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.cell.2022.12.038","article-title":"Human IRF1 governs macrophagic IFN-\u03b3 immunity to mycobacteria","volume":"186","author":"Rosain","year":"2023","journal-title":"Cell"},{"key":"2026082605583600100_B50","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.3389\/fimmu.2019.01176","article-title":"Direct inhibition of IRF-dependent transcriptional regulatory mechanisms associated with disease","volume":"10","author":"Antonczyk","year":"2019","journal-title":"Front Immunol"},{"key":"2026082605583600100_B51","doi-asserted-by":"publisher","first-page":"eabg9518","DOI":"10.1126\/sciadv.abg9518","article-title":"Macrophages orchestrate the expansion of a proangiogenic perivascular niche during cancer progression","volume":"7","author":"Opzoomer","year":"2021","journal-title":"Sci Adv"},{"key":"2026082605583600100_B52","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.immuni.2013.08.009","article-title":"Synergistic activation of inflammatory cytokine genes by interferon-\u03b3-induced chromatin remodeling and toll-like receptor signaling","volume":"39","author":"Qiao","year":"2013","journal-title":"Immunity"},{"key":"2026082605583600100_B53","doi-asserted-by":"publisher","first-page":"3320","DOI":"10.1038\/s41467-019-11147-3","article-title":"IFN-\u03b3 selectively suppresses a subset of TLR4-activated genes and enhancers to potentiate macrophage activation","volume":"10","author":"Kang","year":"2019","journal-title":"Nat Commun"},{"key":"2026082605583600100_B54","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.immuni.2017.12.010","article-title":"The transcription factor STAT6 mediates direct repression of inflammatory enhancers and limits activation of alternatively polarized macrophages","volume":"48","author":"Czimmerer","year":"2018","journal-title":"Immunity"},{"key":"2026082605583600100_B55","doi-asserted-by":"publisher","article-title":"Beyond antagonism: IL-4 exploits TNF signaling to shape its gene expression signature in monocytes and macrophages","author":"Yuan","DOI":"10.1101\/2025.07.28.667180"},{"key":"2026082605583600100_B56","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/s41392-024-01980-4","article-title":"The multiple roles of interferon regulatory factor family in health and disease","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"2026082605583600100_B57","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.imbio.2017.10.005","article-title":"The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2","volume":"223","author":"Chistiakov","year":"2018","journal-title":"Immunobiology"},{"key":"2026082605583600100_B58","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1038\/s41590-019-0466-2","article-title":"Interferon target-gene expression and epigenomic signatures in health and disease","volume":"20","author":"Barrat","year":"2019","journal-title":"Nat Immunol"},{"key":"2026082605583600100_B59","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/ni1576","article-title":"TNF activates an IRF1-dependent autocrine loop leading to sustained expression of chemokines and STAT1-dependent type I interferon\u2013response genes","volume":"9","author":"Yarilina","year":"2008","journal-title":"Nat Immunol"},{"key":"2026082605583600100_B60","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3892\/ijmm.2016.2583","article-title":"Effects of IRF1 and IFN-\u03b2 interaction on the M1 polarization of macrophages and its antitumor function","volume":"38","author":"XIE","year":"2016","journal-title":"Int J Mol Med"},{"key":"2026082605583600100_B61","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/s41590-025-02137-3","article-title":"IL-10 targets IRF transcription factors to suppress IFN and inflammatory response genes by epigenetic mechanisms","volume":"26","author":"Mishra","year":"2025","journal-title":"Nat Immunol"},{"key":"2026082605583600100_B62","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1172\/JCI14097","article-title":"CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation","volume":"109","author":"Ma","year":"2002","journal-title":"J Clin Invest"},{"key":"2026082605583600100_B63","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1111\/j.1398-9995.2010.02431.x","article-title":"Robust expression of CCR3 as a single basophil selection marker in flow cytometry","volume":"66","author":"Hausmann","year":"2011","journal-title":"Allergy"},{"key":"2026082605583600100_B64","doi-asserted-by":"publisher","first-page":"3351","DOI":"10.1128\/JVI.72.4.3351-3361.1998","article-title":"Role of the \u03b2-chemokine receptors CCR3 and CCR5 in human immunodeficiency virus type 1 infection of monocytes and microglia","volume":"72","author":"Ghorpade","year":"1998","journal-title":"J Virol"},{"key":"2026082605583600100_B65","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.7150\/ijbs.127341","article-title":"CCL24 recruits CCR3 + TAMs to promote immunosuppression via YAP1 activation and serves as a therapeutic target for Gracillin in colorectal cancer","volume":"22","author":"Huang","year":"2026","journal-title":"Int J Biol Sci"},{"key":"2026082605583600100_B66","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/978-3-030-62658-7_7","article-title":"CCL24 Signaling in the tumor microenvironment","volume-title":"Adv Exp Med Biol","author":"Lim","year":"2021"},{"key":"2026082605583600100_B67","doi-asserted-by":"publisher","first-page":"10374","DOI":"10.1038\/s41598-022-14610-2","article-title":"A comprehensive bioinformatics analysis to identify potential prognostic biomarkers among CC and CXC chemokines in breast cancer","volume":"12","author":"Hozhabri","year":"2022","journal-title":"Sci Rep"},{"key":"2026082605583600100_B68","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/s41420-022-01227-7","article-title":"Loss of LXN promotes macrophage M2 polarization and PD-L2 expression contributing cancer immune-escape in mice","volume":"8","author":"Li","year":"2022","journal-title":"Cell Death Discov"},{"key":"2026082605583600100_B69","doi-asserted-by":"publisher","first-page":"73","DOI":"10.3892\/or.2022.8284","article-title":"Differential expression of PDL1 and PDL2 is associated with the tumor microenvironment of TILs and M2 TAMs and tumor differentiation in nonsmall cell lung cancer","volume":"47","author":"Sumitomo","year":"2022","journal-title":"Oncol Rep"},{"key":"2026082605583600100_B70","doi-asserted-by":"publisher","first-page":"1093716","DOI":"10.3389\/fimmu.2023.1093716","article-title":"Pan-cancer analysis identifies PD-L2 as a tumor promotor in the tumor microenvironment","volume":"14","author":"Lv","year":"2023","journal-title":"Front Immunol"},{"key":"2026082605583600100_B71","doi-asserted-by":"publisher","first-page":"3311","DOI":"10.1182\/blood-2010-02-271981","article-title":"Alternatively activated macrophages inhibit T-cell proliferation by Stat6-dependent expression of PD-L2","volume":"116","author":"Huber","year":"2010","journal-title":"Blood"},{"key":"2026082605583600100_B72","doi-asserted-by":"publisher","first-page":"5336","DOI":"10.1073\/pnas.0931259100","article-title":"PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells","volume":"100","author":"Loke","year":"2003","journal-title":"Proc Natl Acad Sci"},{"key":"2026082605583600100_B73","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1038\/cmi.2017.17","article-title":"B7-DC (PD-L2) costimulation of CD4+ T-helper 1 response via RGMb","volume":"15","author":"Nie","year":"2018","journal-title":"Cell Mol Immunol"},{"key":"2026082605583600100_B74","doi-asserted-by":"publisher","first-page":"166611","DOI":"10.1016\/j.bbadis.2022.166611","article-title":"KDM6B regulates M2 polarization of macrophages by modulating the stability of nuclear \u03b2-catenin","volume":"1869","author":"Du","year":"2023","journal-title":"Biochim Biophys Acta"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/54\/16\/gkag825\/70792446\/gkag825.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/54\/16\/gkag825\/70792446\/gkag825.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:58:45Z","timestamp":1787738325000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/doi\/10.1093\/nar\/gkag825\/8770895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":74,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2026,8,24]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkag825","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9,9]]},"published":{"date-parts":[[2026,8,24]]},"article-number":"gkag825"}}