{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:19:07Z","timestamp":1785424747373,"version":"3.56.0"},"posted":{"date-parts":[[2025,8,28]]},"group-title":"Immunology","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["DE028296"],"award-info":[{"award-number":["DE028296"]}],"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DE028031"],"award-info":[{"award-number":["DE028031"]}],"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["GM125504"],"award-info":[{"award-number":["GM125504"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The leukocyte NADPH oxidase 2 (NOX2) is an important regulator of inflammatory responses, independent of its antimicrobial activity. Inactivating mutations in NOX2 cause chronic granulomatous disease (CGD), a severe immunodeficiency associated with recurrent infections and dysregulated neutrophilic inflammation. Recurrent oral ulcers, stomatitis, gingivitis, and other inflammatory issues affecting the oral mucosa have been observed in patients with CGD; however, the underlying mechanisms are not known. Here, we present evidence that the extensive inflammatory destruction of oral mucosal tissues observed in Nox2-deficient or\n                  <jats:italic>\n                    Cybb\n                    <jats:sup>KO<\/jats:sup>\n                  <\/jats:italic>\n                  mice was not caused by impaired antimicrobial surveillance against oral pathobionts but instead resulted from a cell-intrinsic dysregulation of neutrophil inflammatory responses. Transcriptional and cellular profiling of oral tissues isolated from wild-type and\n                  <jats:italic>\n                    Cybb\n                    <jats:sup>KO<\/jats:sup>\n                  <\/jats:italic>\n                  mice showed a dominant neutrophil signature, which was accompanied by a significant upregulation of several bone-resorbing, tissue-degrading inflammatory cytokines and a reduced expression of nuclear factor erythroid 2-related factor 2 (Nrf2) regulated genes. Mechanistically, hyperinflammatory responses were mitigated by restoring Nrf2 transcriptional activity using a synthetic agonist. Thus, our studies show that Nox2 oxidase and its derived reactive oxygen species are crucial for balanced recruitment and cell-intrinsic regulation of neutrophil inflammatory responses within oral tissues in an Nrf2-dependent manner.\n                <\/jats:p>","DOI":"10.1101\/2025.08.26.671820","type":"posted-content","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T01:10:26Z","timestamp":1756429826000},"source":"Crossref","is-referenced-by-count":0,"title":["The Nox2 NADPH oxidase regulates neutrophilic inflammation in the oral cavity"],"prefix":"10.64898","author":[{"given":"Shunying","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Singhal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhu","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelley N","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Terekhova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A","family":"Carey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1133-4212","authenticated-orcid":false,"given":"Maxim N","family":"Artyomov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatakrishna R","family":"Jala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A","family":"Idol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary C","family":"Dinauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J","family":"Lamont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6185-1915","authenticated-orcid":false,"given":"Juhi","family":"Bagaitkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025090202301231000_2025.08.26.671820v1.1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-844563"},{"key":"2025090202301231000_2025.08.26.671820v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2019.05.006"},{"key":"2025090202301231000_2025.08.26.671820v1.3","first-page":"390","article-title":"Relation of monocyte and neutrophil oxidative metabolism to skin and oral lesions in carriers of chronic granulomatous disease","volume":"43","year":"1981","journal-title":"Clin Exp Immunol"},{"key":"2025090202301231000_2025.08.26.671820v1.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1981.tb08163.x"},{"key":"2025090202301231000_2025.08.26.671820v1.5","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e3182481ed9"},{"key":"2025090202301231000_2025.08.26.671820v1.6","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-3-37"},{"key":"2025090202301231000_2025.08.26.671820v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.08.005"},{"key":"2025090202301231000_2025.08.26.671820v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01219-w"},{"key":"2025090202301231000_2025.08.26.671820v1.9","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12252"},{"key":"2025090202301231000_2025.08.26.671820v1.10","doi-asserted-by":"publisher","DOI":"10.1177\/1753425916668980"},{"key":"2025090202301231000_2025.08.26.671820v1.11","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003525"},{"key":"2025090202301231000_2025.08.26.671820v1.12","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2003.02138.x"},{"key":"2025090202301231000_2025.08.26.671820v1.13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009631"},{"key":"2025090202301231000_2025.08.26.671820v1.14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2001298"},{"key":"2025090202301231000_2025.08.26.671820v1.15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1322831111"},{"key":"2025090202301231000_2025.08.26.671820v1.16","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-05-644773"},{"key":"2025090202301231000_2025.08.26.671820v1.17","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007652"},{"key":"2025090202301231000_2025.08.26.671820v1.18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.2.207"},{"key":"2025090202301231000_2025.08.26.671820v1.19","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-160564"},{"key":"2025090202301231000_2025.08.26.671820v1.20","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202x.2001.01691.x"},{"key":"2025090202301231000_2025.08.26.671820v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/ng0295-202"},{"key":"2025090202301231000_2025.08.26.671820v1.22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200543"},{"key":"2025090202301231000_2025.08.26.671820v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2013.05.002"},{"key":"2025090202301231000_2025.08.26.671820v1.24","doi-asserted-by":"publisher","DOI":"10.3791\/53736"},{"key":"2025090202301231000_2025.08.26.671820v1.25","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2007.060252"},{"key":"2025090202301231000_2025.08.26.671820v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06234-9"},{"key":"2025090202301231000_2025.08.26.671820v1.27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.02950.x"},{"key":"2025090202301231000_2025.08.26.671820v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2016.02.002"},{"key":"2025090202301231000_2025.08.26.671820v1.29","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuad018"},{"key":"2025090202301231000_2025.08.26.671820v1.30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01065"},{"key":"2025090202301231000_2025.08.26.671820v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3669"},{"key":"2025090202301231000_2025.08.26.671820v1.32","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12065"},{"key":"2025090202301231000_2025.08.26.671820v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/S1521-6616(02)00048-7"},{"key":"2025090202301231000_2025.08.26.671820v1.34","doi-asserted-by":"publisher","DOI":"10.1097\/PG9.0000000000000047"},{"key":"2025090202301231000_2025.08.26.671820v1.35","doi-asserted-by":"publisher","DOI":"10.1093\/jpids\/piy007"},{"key":"2025090202301231000_2025.08.26.671820v1.36","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01605-07"},{"key":"2025090202301231000_2025.08.26.671820v1.37","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.6.1253"},{"key":"2025090202301231000_2025.08.26.671820v1.38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201809"},{"key":"2025090202301231000_2025.08.26.671820v1.39","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-272005"},{"key":"2025090202301231000_2025.08.26.671820v1.40","doi-asserted-by":"publisher","DOI":"10.1093\/jleuko\/qiae209"},{"key":"2025090202301231000_2025.08.26.671820v1.41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007773"},{"key":"2025090202301231000_2025.08.26.671820v1.42","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00197"},{"key":"2025090202301231000_2025.08.26.671820v1.43","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15803"},{"key":"2025090202301231000_2025.08.26.671820v1.44","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00012.2018"},{"key":"2025090202301231000_2025.08.26.671820v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.11.020"},{"key":"2025090202301231000_2025.08.26.671820v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11624"},{"key":"2025090202301231000_2025.08.26.671820v1.47","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17111907"},{"key":"2025090202301231000_2025.08.26.671820v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.09.006"},{"key":"2025090202301231000_2025.08.26.671820v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.01.013"},{"key":"2025090202301231000_2025.08.26.671820v1.50","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13171"},{"key":"2025090202301231000_2025.08.26.671820v1.51","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3VMR1014-468R"},{"key":"2025090202301231000_2025.08.26.671820v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.disamonth.2022.101356"},{"key":"2025090202301231000_2025.08.26.671820v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2014.11.004"},{"key":"2025090202301231000_2025.08.26.671820v1.54","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0089-x"},{"key":"2025090202301231000_2025.08.26.671820v1.55","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07808-5"},{"key":"2025090202301231000_2025.08.26.671820v1.56","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.2006.00178.x"},{"key":"2025090202301231000_2025.08.26.671820v1.57","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03276.x"},{"key":"2025090202301231000_2025.08.26.671820v1.58","doi-asserted-by":"publisher","DOI":"10.1007\/s000180300001"},{"key":"2025090202301231000_2025.08.26.671820v1.59","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-09-809004"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.08.26.671820","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:11:52Z","timestamp":1782277912000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.08.26.671820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,28]]},"references-count":59,"URL":"https:\/\/doi.org\/10.1101\/2025.08.26.671820","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.mucimm.2026.04.002","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,8,28]]},"subtype":"preprint"}}