ITGAX promotes Th17-cell differentiation and drives pathogenesis in pediatric ulcerative colitis

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dc.contributor.authorDong Zhan
dc.contributor.authorWanying Xie
dc.contributor.departmentBiología Celular e Histología
dc.date.accessioned2026-01-07T16:17:58Z
dc.date.available2026-01-07T16:17:58Z
dc.date.issued2026
dc.description.abstractBackground. Pediatric ulcerative colitis (UC) is an inflammatory bowel disease characterized by dysregulated immune responses and intestinal inflammation, often more severe than adult-onset UC. Th17 cells play a crucial role in UC pathogenesis but the mechanisms regulating their differentiation and recruitment in pediatric UC remain incompletely understood. Methods. Transcriptomic analysis of pediatric UC patients and weighted gene co-expression network analysis (WGCNA) were performed to identify key dysregulated genes. The functional role of the candidate gene ITGAX was investigated using in vitro Th17 differentiation assays with siRNA knockdown and an in vivo dextran sodium sulfate (DSS)-induced UC mouse model with intrarectal siRNA administration. Results. WGCNA identified ITGAX, SOCS3, CXCL1, CASP1, and CXCL11 as core upregulated genes in pediatric UC, with ITGAX being a novel candidate regulator of Th17 cells. ITGAX knockdown in naive CD4+ T cells impaired Th17 differentiation and IL-17A production in vitro. In the DSS-induced UC mouse model, intrarectal ITGAX siRNA ameliorated colonic inflammation and ulceration, suppressed IL-17A levels, and selectively reduced the expansion of IFNγ-IL-17+ Th17 cells in the colon. Conclusion. ITGAX is a key promoter of Th17-cell differentiation and expansion, contributing to the pathogenesis of pediatric UC. Targeting ITGAX may represent a potential therapeutic strategy for pediatric UC by modulating aberrant Th17 responses.
dc.formatapplication/pdf
dc.format.extent13
dc.identifier.doihttps://doi.org/10.14670/HH-18-899
dc.identifier.eissn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/184249
dc.languageeng
dc.publisherUniversidad de Murcia, Departamento de Biologia Celular e Histiologia
dc.relationSin financiacion externa a la Universidad
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectTh17 cells
dc.subjectITGAX
dc.subjectTranscriptomics
dc.subjectInflammatory bowel disease
dc.subjectPediatric ulcerative colitis
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleITGAX promotes Th17-cell differentiation and drives pathogenesis in pediatric ulcerative colitis
dc.typeinfo:eu-repo/semantics/article
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Histology and histopathology, Vol.41, Nº2, (2026)