{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:22:23Z","timestamp":1793146943979,"version":"4.5.0"},"reference-count":89,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Immunopathol Pharmacol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>The oral epithelium is a dynamic interface between host and environment, where keratinocytes not only serve as structural components but also actively modulate immune responses. Emerging research identifies IRF6 as a pivotal regulator of epithelial differentiation and immune signaling within chronic inflammatory contexts. This narrative review explores the role of IRF6 and its downstream effects in oral keratinocytes, particularly in relation to Toll-like receptor (TLR) activation, CCL5-mediated inflammation, hypoxic signaling, and the epithelial-mesenchymal transition (EMT). It proposes a mechanistic framework for understanding the progression from chronic inflammation to epithelial disruption and malignant transformation in oral mucosal disorders. Modulation of IRF6 signaling represents a promising therapeutic target for restoring epithelial integrity and halting disease progression in chronic inflammatory oral diseases. This model lays groundwork for future research integrating molecular biomarkers and immune modulation strategies in oral pathology.<\/jats:p>","DOI":"10.1177\/03946320251411432","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T07:06:28Z","timestamp":1767683188000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Oral keratinocyte-mediated inflammation and epithelial disruption: A narrative review on IRF6 signaling and oral carcinogenic risk"],"prefix":"10.1177","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6036-0479","authenticated-orcid":false,"given":"Yuliana Andrea","family":"Osorio-Osorno","sequence":"first","affiliation":[{"name":"School of Dentistry, Universidad de Antioquia, Medell\u00edn, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6516-1540","authenticated-orcid":false,"given":"Monica Tatiana","family":"Parada-Sanchez","sequence":"additional","affiliation":[{"name":"School of Dentistry, Universidad de Antioquia, Medell\u00edn, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.disamonth.2020.100988"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2021.105451"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.22941.1"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2023.104112"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.04.029"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01078.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.61"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12185"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-021-09188-2"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2021.06.031"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.job.2020.05.003"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12094"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1177\/10454411900010030201"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1177\/00220345670460064801"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2015.0325"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsc.2016.08.008"},{"key":"e_1_3_2_18_2","first-page":"9","article-title":"Knowledge of oral mucosa as a tarjet organ to induce pharma-immunotherapy","volume":"48","author":"Casariego Z","year":"2017","unstructured":"Casariego Z, P\u00e9rez A (2017) Knowledge of oral mucosa as a tarjet organ to induce pharma-immunotherapy. Archivos de alergia e inmunolog\u00eda clinica 48: 9\u201320.","journal-title":"Archivos de alergia e inmunolog\u00eda clinica"},{"issue":"9","key":"e_1_3_2_19_2","first-page":"816","article-title":"Radioautographic studies with 3H-thymidine on the regeneration of epithelial attachments","volume":"24","author":"Kirschner H","year":"1969","unstructured":"Kirschner H, R\u00fchl E (1969) Radioautographic studies with 3H-thymidine on the regeneration of epithelial attachments. Deutsche zahnarztliche Zeitschrift 24(9): 816\u2013824.","journal-title":"Deutsche zahnarztliche Zeitschrift"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.2006.00157.x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.22.010305.104219"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOMG.0000017431.45314.07"},{"issue":"6","key":"e_1_3_2_23_2","first-page":"685","article-title":"Intestinal barrier function","volume":"5","author":"Baumgart DC","year":"2002","unstructured":"Baumgart DC, Dignass AU (2002) Intestinal barrier function. Current Opinion in Clinical Nutrition and Metabolic Care 5(6): 685\u2013694.","journal-title":"Current Opinion in Clinical Nutrition and Metabolic Care"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.0022-0337.2002.66.4.tb03536.x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.129.5.1329"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1606272113"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2927"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2008.03.001"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.2.687-694.2005"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/eos.12074"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-020-01118-2"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00464"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-9255-2-16"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013027"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2011.10.013"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12655"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25439"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034517723615"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng985"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjorl.2019.04.011"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1097\/SCS.0b013e3181ec6aad"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0132757"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1894"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.584540"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01866-07"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.272"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.325"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1110931108"},{"key":"e_1_3_2_49_2","first-page":"1","article-title":"Mammary serine protease inhibitor (Maspin) binds directly to interferon regulatory factor 6: Identification of novel serpin partnership","volume":"48","author":"Bailey CM","year":"2005","unstructured":"Bailey CM, Khalkhali-Ellis Z, Kondo S, et al. (2005) Mammary serine protease inhibitor (Maspin) binds directly to interferon regulatory factor 6: Identification of novel serpin partnership. The Journal of Biological Chemistry 48(Suppl. 2): 1\u20136.","journal-title":"The Journal of Biological Chemistry"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.13.6221"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2016.1336"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007158"},{"key":"e_1_3_2_53_2","first-page":"1","article-title":"IRF6 is directly regulated by ZEB1 and ELF3, and predicts a favorable prognosis in gastric cancer","volume":"9","author":"Li D","year":"2019","unstructured":"Li D, Cheng P, Wang J, et al. (2019) IRF6 is directly regulated by ZEB1 and ELF3, and predicts a favorable prognosis in gastric cancer. Frontiers in Oncology 9: 1\u201312.","journal-title":"Frontiers in Oncology"},{"key":"e_1_3_2_54_2","volume-title":"Dissecting the Role of the Major Cleft Gene, IRF6, in Primary Palatal Epithelia","author":"Parada Sanchez MT","year":"2012","unstructured":"Parada Sanchez MT (2012) Dissecting the Role of the Major Cleft Gene, IRF6, in Primary Palatal Epithelia. Seattle: University of Washington."},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2016.03.005"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2015.77"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501263"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00858-16"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12071765"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2021.08.004"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-02-0488"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13235947"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.45.32478"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.13.7222"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2013.837886"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40266"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40267"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep12791"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13123027"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2020.100773"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.718066"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1903"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.4103\/aam.aam_56_18"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.122390"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.17.1.f132"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.200900043"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01332-8"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-53593-8"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1187"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1080\/20002297.2018.1563410"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.4248\/IJOS11075"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.05.004"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-023-05443-1"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.08.002"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.2174\/1574892813666180227103147"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1007\/s42452-025-07571-4"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1080\/20002297.2022.2105574"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-024-00511-x"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2019.08.013"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-024-01386-4"}],"container-title":["International Journal of Immunopathology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03946320251411432","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/03946320251411432","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03946320251411432","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:01:15Z","timestamp":1777456875000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/03946320251411432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":89,"alternative-id":["10.1177\/03946320251411432"],"URL":"https:\/\/doi.org\/10.1177\/03946320251411432","relation":{},"ISSN":["0394-6320","2058-7384"],"issn-type":[{"value":"0394-6320","type":"print"},{"value":"2058-7384","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"article-number":"03946320251411432"}}