{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:33:16Z","timestamp":1780403596486,"version":"3.54.1"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Interleukin\u20104 (IL\u20104) drives Th2 polarisation and allergic inflammation, yet the epigenetic mechanisms regulating\n                    <jats:italic>Il4<\/jats:italic>\n                    transcription in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells remain unclear. While STAT6 and GATA3 are canonical transcriptional regulators, lysine\u2010specific demethylase 5A (KDM5A), an H3K4\u2010specific demethylase, has not been linked to Th2 immunity. Here, we investigate KDM5A's role in IL\u20104 production and allergic airway disease (AA). Using DO11.10 TCR\u2010transgenic mice and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2010specific Kdm5a\u2010knockout models, we assessed KDM5A's role in IL\u20104 transcription. Chromatin immunoprecipitation (ChIP)\u2010qPCR evaluated H3K4 demethylation at the Il4 promoter. Cross\u2010ELISA quantified IL\u20104 secretion, and ubiquitination assays analysed KDM5A stability. Lactobacilli\u2010derived DNA (LgDNA) was administered to disrupt the USP7\u2010KDM5A axis in AA models. The results showed that KDM5A deficiency abolished TCR activation\u2010induced IL\u20104 production, impairing Th2 polarisation. Mechanistically, KDM5A maintained H3K4 hypomethylation at the\n                    <jats:italic>Il4<\/jats:italic>\n                    promoter, facilitating STAT6\/GATA3 recruitment. TCR signalling enhanced KDM5A promoter occupancy via USP7\u2010mediated deubiquitination. USP7 stabilisation of KDM5A elevated H3K4 demethylation and IL\u20104 transcription, driving AA pathogenesis. LgDNA suppressed USP7 activity, reducing KDM5A promoter binding by 65% and airway inflammation by 72%. In summary, KDM5A acts as an epigenetic rheostat of Th2 immunity, where USP7\u2010dependent stabilisation licenses STAT6\/GATA3 access to the\n                    <jats:italic>Il4<\/jats:italic>\n                    promoter during TCR activation. Targeting the USP7\u2010KDM5A axis with LgDNA selectively suppresses pathogenic Th2 responses while preserving physiological IL\u20104 functions. Our findings define a novel epigenetic mechanism for allergic disease and establish microbiome\u2010derived LgDNA as a precision therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1111\/imm.70061","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T02:07:02Z","timestamp":1762308422000},"page":"467-480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>KDM5A<\/scp>\n                    : A Master Epigenetic Regulator of Th2 Immunity and Allergic Disease Pathogenesis"],"prefix":"10.1111","volume":"177","author":[{"given":"Jiangqi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Allergy Longgang ENT Hospital &amp; Shenzhen ENT Institute  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Allergy Longgang ENT Hospital &amp; Shenzhen ENT Institute  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorui","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Allergy Longgang ENT Hospital &amp; Shenzhen ENT Institute  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Allergy Longgang ENT Hospital &amp; Shenzhen ENT Institute  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of General Practice Medicine Third Affiliated Hospital of Shenzhen University (Luohu Hospital)  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of General Practice Medicine Third Affiliated Hospital of Shenzhen University (Luohu Hospital)  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Practice Medicine Third Affiliated Hospital of Shenzhen University (Luohu Hospital)  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6806-9464","authenticated-orcid":false,"given":"Pingchang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of General Practice Medicine Third Affiliated Hospital of Shenzhen University (Luohu Hospital)  Shenzhen China"},{"name":"State Key Laboratory of Respiratory Diseases Allergy Division at Shenzhen University and Institute of Allergy &amp; Immunology, Shenzhen University School of Medicine, Shenzhen Key Laboratory of Allergy &amp; Immunology  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.02.016"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v37.i2-6.30"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1398-9995.2000.00511.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10113000"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.01.020"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00186.2019"},{"key":"e_1_2_11_8_1","article-title":"Histone Demethylase Enzymes KDM5A and KDM5B Modulate Immune Response by Suppressing Transcription of Endogenous Retroviral Elements","volume":"2024","author":"Chen H.","year":"2024","journal-title":"bioRxiv"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.03.035"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi3664"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052412"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01041-1"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2023.2268813"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-024-01940-2"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114730"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31881"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201646799"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12223"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117872"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abm9454"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2302903120"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.13444"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115231"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aat1604"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.018"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113855"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-022-23091-9"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-022-09754-w"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2020.1766345"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.70061","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.70061","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.70061","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:28:35Z","timestamp":1771028915000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.70061"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/imm.70061"],"URL":"https:\/\/doi.org\/10.1111\/imm.70061","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]},"assertion":[{"value":"2025-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}