Mucosal Immunology最新文献

{"title":"Human enteric defensin 5 protects intestinal barrier integrity via cell state–dependent P2Y11–FAK–Rac1 signaling","authors":"Mengyao Guo,&nbsp;Yaqian Zhang,&nbsp;Yaxin Liu,&nbsp;Chenyi Mao,&nbsp;Xin Xu,&nbsp;Yang Shen,&nbsp;Ruifen Zhang,&nbsp;Qingxia Wang,&nbsp;Wuyuan Lu,&nbsp;Kai Ye,&nbsp;Dan Xu","doi":"10.1016/j.mucimm.2026.100350","DOIUrl":"10.1016/j.mucimm.2026.100350","url":null,"abstract":"<div><div>Human enteric α-defensin 5 (HD5) is an antimicrobial peptide and a key effector of intestinal mucosal innate immunity. Paradoxically, HD5 has also been shown to enhance <em>Shigella</em> infection by inducing filopodia-like extensions via activation of the P2Y11 receptor. However, the broader physiological significance of the HD5–P2Y11 interaction remains poorly understood. Here, using primary human colonic epithelial cells, human colonic organoids, and a gut-on-a-chip model, we uncover a previously unappreciated role of HD5 in establishing and preserving the human intestinal barrier by promoting epithelial cell adhesion under stress conditions. Mechanistically, HD5 activates a previously unrecognized P2Y11–FAK signaling axis, leading to phosphorylation of FAK and paxillin and promoting focal adhesion formation, with Rac1 acting downstream to support epithelial adhesion and barrier integrity. Strikingly, this FAK-centered signaling operates independently of PKA, revealing a cell state–dependent bifurcation in HD5–P2Y11 signaling: in well-adhered epithelial cells, HD5 engages PKA to induce exploratory protrusions, whereas in suspended or injured epithelial cells, HD5 preferentially engages FAK to restore adhesion and reinforce barrier integrity. Together, these results identify HD5 as a human-specific epithelial signaling molecule that links innate immune defense to epithelial adhesion dynamics and contributes to mucosal barrier homeostasis.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100350"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ILC2s govern imprinting of alveolar macrophage-mediated immune responses upon secondary helminth infection in the lung","authors":"Jonathan Pollock,&nbsp;Jhanvi H. Patel,&nbsp;Lisa-Marie Graf,&nbsp;Andreas Ruhl,&nbsp;Daniel Radtke,&nbsp;David Voehringer","doi":"10.1016/j.mucimm.2026.100367","DOIUrl":"10.1016/j.mucimm.2026.100367","url":null,"abstract":"<div><div>Hookworms migrate through the lung as part of their lifecycle, causing significant tissue damage that activates tissue-resident populations such as ILC2s. These drive type 2 immune responses critical for wound healing and the development of protective immunity. Monocyte-derived macrophages that seed the lung after infection are central effectors of these responses, but the cellular and molecular factors guiding their development and function remain poorly understood. We find that ILC2s and IL-4/IL-13-producing CD4⁺ T cells regulate alveolar macrophage populations during helminth infection. In their absence, anti-parasitic immunity is impaired during secondary infection and the expansion of type 2-polarized monocyte-derived alveolar macrophages (Mo-AMs) is diminished. While Mo-AMs highly expressed Arg1, this was not essential for development of immunity. Concomitant with a distinct metabolic and transcriptional profile, ILC2-induced Mo-AMs selectively upregulated arachidonate 15-lipoxygenase which promoted anti-parasitic responses in vitro. Our results identify ILC2s and Th2 cells as critical regulators of alveolar macrophage dynamics and function during helminth infection.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100367"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eomes fate-labeling reveals a subset of Eomeslo NK cells that exhibits an ILC1-like phenotype","authors":"Vladislava Stokic-Trtica,&nbsp;Johannes Steffen,&nbsp;Xuemei Gao,&nbsp;Henning Peter Düsedau,&nbsp;Sotiria Boulekou,&nbsp;Sebastian J. Arnold,&nbsp;Antigoni Triantafyllopoulou,&nbsp;Chiara Romagnani,&nbsp;Andreas Diefenbach,&nbsp;Yakup Tanriver,&nbsp;Ildiko R. Dunay,&nbsp;Christoph S.N. Klose","doi":"10.1016/j.mucimm.2026.04.003","DOIUrl":"10.1016/j.mucimm.2026.04.003","url":null,"abstract":"<div><div>Innate lymphoid cells (ILCs) are distinct lineages defined by lineage-specifying transcription factors that drive their differentiation and effector programs. Despite being stable lineages, ILC plasticity has been reported. Plasticity is characterized by downregulation of the transcription factor that specifies the current ILC lineage, followed by upregulation of the transcription factor and surface markers that determine the phenotype of the new ILC lineage. Even though NK cells rely on the lineage-specifying transcription factor Eomes, an unusual phenotype characterized by ILC1 marker expression was reported in the salivary glands and during <em>Toxoplasma gondii</em> infection. However, it remains unclear whether this reflects true ILC plasticity or simply phenotypic changes. Using a dual-reporter system that allows simultaneous detection of live expression and fate-labeling of Eomes, we observed downregulation of this lineage-specifying transcription factor in NK cells (Eomes^lo cells) and upregulation of ILC1 markers in the salivary gland and multiple organs during <em>Toxoplasma gondii</em> infection, including organs that otherwise promote NK cell fate. While Eomes^lo cells adopted an ILC1-like phenotype, they differentiated in the absence of Hobit, a pivotal transcription factor of ILC1s, distinguishing them from the ILC1 lineage. Therefore, our data demonstrate that NK cells can adopt an Eomes^lo ILC1-like fate, even in the blood and secondary lymphoid organs, complementing previous findings on ILC2 and ILC3 plasticity towards the ILC1 lineage.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100342"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine networks driving eosinophil functional heterogeneity","authors":"James I. King,&nbsp;Isabelle C. Arnold","doi":"10.1016/j.mucimm.2026.100347","DOIUrl":"10.1016/j.mucimm.2026.100347","url":null,"abstract":"<div><div>Eosinophils have traditionally been viewed as terminally differentiated type 2 effector cells involved in anti-helminth immunity and allergic inflammation. Recent advances in single-cell transcriptomics have refined this view, revealing substantial developmental and functional heterogeneity across tissues and inflammatory settings. Eosinophil development in the bone marrow is controlled by lineage-defining transcription factors and by cytokines such as IL-5, IL-3, GM-CSF and IL-33, which regulate progenitor expansion, maturation, mobilization and survival. After entering tissues, eosinophils integrate local cytokine, stromal, epithelial, microbial and metabolic signals to acquire context-dependent activation states.</div><div>In this review, we summarize core developmental programs of eosinophils and examine how cytokine networks shape their responses across type 1, type 2 and type 17 immunity. We discuss evidence that eosinophils contribute not only to classical type 2 responses, but also to antimicrobial, cytotoxic, immunoregulatory and tissue-remodeling programs in non-type 2 settings, positioning them as highly plastic effectors with broad roles in host defense, tissue homeostasis and disease.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100347"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SENP1 facilitates the adaptation of colonic non-lymphoid tissue Treg cells and restrains intestinal inflammation","authors":"Yanyun Hao,&nbsp;Hongzhi Liu,&nbsp;Qiuli Liang,&nbsp;Qiuju Fan,&nbsp;Tianshi Wang,&nbsp;Jinke Cheng","doi":"10.1016/j.mucimm.2026.100349","DOIUrl":"10.1016/j.mucimm.2026.100349","url":null,"abstract":"<div><div>Colonic immune homeostasis is critically maintained by regulatory T (Treg) cells. Here, we identify SUMO-specific peptidase 1 (SENP1) as an important regulator of colonic Treg function and intestinal immune homeostasis. Treg-specific <em>Senp1</em> deletion does not impair thymic Treg development, but selectively disrupts the homeostasis of colonic Treg subset without affecting Treg maintenance in other peripheral tissues. Mechanistically, SENP1 deficiency reduces CD25 expression on Tregs, blunting IL-2 responsiveness and compromising their expansion and survival. This is associated with a selective reduction in the proportion of tissue-adapted Gata3^hi Tregs and accumulation of CD25^lo precursor-like Tregs in the intestinal lamina propria. <em>Senp1</em> depletion also downregulates core effector Treg signature genes including <em>Gata3</em>, <em>Klrg1</em>, and <em>Il1rl1</em>, correlating with dysregulated Th2 response control. Single-cell RNA sequencing analysis reveals transcriptional alterations consistent with impaired colonic Treg tissue adaptation after SENP1 ablation. Functionally, with adoptive transfer experiments we found that <em>Senp1</em>-deficient Tregs show impaired accumulation in vivo and are associated with weaker control of pathogenic T cell expansion in the colon. Consistently, Treg-specific <em>Senp1</em>-deficient mice display heightened susceptibility to DSS-induced colitis, highlighting a critical role of SENP1 in sustaining functional Treg programs and limiting pathogenic intestinal inflammation.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100349"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tuft cells protect against intestinal inflammation through histone deacetylase 3","authors":"Emily M. Eshleman,&nbsp;Taylor Rice,&nbsp;Amanda Waddell,&nbsp;Samarth Kumar,&nbsp;Bailey J. Didriksen,&nbsp;Laura Engleman,&nbsp;Sybele Vidyant,&nbsp;Mohammed Sayed,&nbsp;Rebekah Karns,&nbsp;Hee-Woong Lim,&nbsp;Lee A. Denson,&nbsp;Theresa Alenghat","doi":"10.1016/j.mucimm.2026.100356","DOIUrl":"10.1016/j.mucimm.2026.100356","url":null,"abstract":"<div><div>While intestinal tuft cells are well known to promote type 2 immunity, their role in inflammatory bowel disease (IBD) remains unclear. Here, we show that tuft cells are reduced in the distal intestine of pediatric IBD patients and that tuft cell-deficient mice exhibited increased susceptibility to intestinal inflammation. Histone deacetylase 3 (HDAC3) expression in intestinal stem cells is essential for tuft cell differentiation. Interestingly, single-cell analyses revealed that HDAC3 was also enriched in mature tuft cells compared to other differentiated epithelial populations. Generation of tuft cell-specific HDAC3 knockout mice (HDAC3^ΔTuft) showed that expression of canonical tuft cell pathways were impaired in HDAC3^ΔTuft mice, suggesting that HDAC3 regulates tuft cell-intrinsic function. HDAC3^ΔTuft mice did not exhibit a significant difference in tuft cell numbers, however loss of HDAC3 specifically in tuft cells promoted colitis. Transcriptional analyses of ileal and colonic epithelium demonstrated dampened repair responses in HDAC3^ΔTuft mice relative to control mice. Furthermore, HDAC3 inhibition in human colonoids similarly downregulated tuft cell-associated cytokines and eicosanoid pathways that promote epithelial repair. Collectively, these data indicate that enhancing tuft cell function may prevent or treat IBD, and that tuft cell-intrinsic regulation by HDAC3 limits susceptibility to intestinal damage and inflammation.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100356"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virus-specific resident memory T cell networks sustain immunity in human oral mucosa","authors":"Florian Winkler,&nbsp;Carmen Fischer,&nbsp;Laura Marie Gail,&nbsp;Florian Deckert,&nbsp;Lisa Kleissl,&nbsp;Thomas Krausgruber,&nbsp;Kveta Brazdilova,&nbsp;Ana Aguilar González,&nbsp;Georg Stary,&nbsp;Johanna Strobl","doi":"10.1016/j.mucimm.2026.100362","DOIUrl":"10.1016/j.mucimm.2026.100362","url":null,"abstract":"<div><h3>Background</h3><div>Durable protection against viral infections relies on tissue-resident memory T (T_RM) cells at pathogen entry sites. The oral cavity is a critical mucosal barrier frequently exposed to viral pathogens; however, the phenotypic characteristics and spatial organization of virus-specific T cells in the human oral mucosa remain poorly understood.</div></div><div><h3>Objective</h3><div>This study aimed to define how virus-specific T cells maintain long-term residency in the oral mucosa and to identify cellular interactions supporting their persistence.</div></div><div><h3>Methods</h3><div>We profiled predicted virus-specific T cells in the blood and oral mucosa of seven healthy individuals who recently recovered from SARS-CoV-2 infection. Single-cell RNA and T cell receptor sequencing, spatial transcriptomics, and immunofluorescence (IF) were used to define cell composition, localization, and interactions.</div></div><div><h3>Results</h3><div>Cytomegalovirus-specific T cells were predominantly CD4⁺ effector memory T cells, whereas Epstein–Barr virus– and SARS-CoV-2–specific T cells were mainly CD8⁺ T_RM cells with cytotoxic features. Cell–cell communication analysis suggested that predicted virus-specific CD8⁺ T_RM cells were embedded in highly interactive signaling networks, receiving strong inputs from fibroblasts and dendritic cells. Spatial transcriptomics and IF confirmed close associations between CD8⁺ T_RM, fibroblasts, and dendritic cells.</div></div><div><h3>Conclusion</h3><div>Predicted virus-specific CD8⁺ T_RM cells appear to play a prominent role in the human oral mucosa, where supportive communication networks with fibroblasts and dendritic cells likely contribute to their persistence and long-term survival at this critical barrier site.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100362"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148226950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-embedded CD4+ plasticity defines mucosal immunity in inflammatory bowel disease","authors":"Qinyue Jiang,&nbsp;Veerle A. Merkus,&nbsp;Ciska Lindelauf,&nbsp;Jens Krijgsman,&nbsp;Nannan Guo,&nbsp;Laura F. Ouboter,&nbsp;Thomas Höllt,&nbsp;Philip W. Voorneveld,&nbsp;Caroline R. Meijer-Boekel,&nbsp;Frits Koning,&nbsp;Andrea E. van der Meulen-de Jong,&nbsp;Maria Fernanda Pascutti,&nbsp;Vincent van Unen","doi":"10.1016/j.mucimm.2026.100369","DOIUrl":"10.1016/j.mucimm.2026.100369","url":null,"abstract":"<div><div>CD4⁺ T helper (Th) cell responses to commensal microbiota are linked to Inflammatory Bowel Disease (IBD), yet how Th programs coexist and evolve in human tissues remains poorly defined. Here, we profiled CD4⁺ memory T cells in intestinal biopsies using immunological and histological approaches to map phenotypes, functional states, and spatial relationships across disease states. A marked expansion of CD4⁺ T cells concomitant with a RORγt⁺ Th population with elevated T-bet expression was linked to the progression of inflammation. Moreover, Foxp3⁺ cells co-expressing RORγt emerged within the inflamed niche, indicating regulatory–Th17 plasticity. Trajectory visualization revealed a potential branched differentiation path toward regulatory or tissue-resident Th17-like fates, with both termini expressing activation and proliferation markers. Correlation network analysis connected pro-inflammatory CD4⁺ states to T-bet⁺Granzyme-B⁺ CD8⁺ subsets, indicating coordination between helper and cytotoxic lineages. Histology revealed increased T-cell infiltration and spatial segregation of tissue-resident subsets, with CD103⁺CD4⁺ T cells localized mainly in the lamina propria and CD103⁺CD8⁺ T cells near the epithelium. TCR stimulation during active disease revealed broad suppression of CD4⁺ pro-inflammatory cytokines alongside Foxp3⁺ expansion. Conversely, HLA-DR⁺CD38⁺ memory subset retained multifunctionality, producing elevated levels of pro-inflammatory cytokines. Together, these results define a dynamic, tissue-embedded CD4 T-cell landscape in IBD.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100369"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148331437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucosal immunity as a vaccine-induced correlate of protection against influenza","authors":"A.R. Dvorscek,&nbsp;A.S. Kushnir,&nbsp;O. Dibben,&nbsp;G.H. Kijak,&nbsp;R.S. Thwaites","doi":"10.1016/j.mucimm.2026.100381","DOIUrl":"10.1016/j.mucimm.2026.100381","url":null,"abstract":"<div><div>Licensure of influenza vaccines relies on serum hemagglutination inhibition (HAI) titers, a correlate of protection (CoP) that was developed more than 50 years ago and which is only poorly predictive of protection. This is especially true of immunity induced by intranasal live attenuated influenza vaccines (LAIVs). Unlike intramuscular inactivated influenza vaccines (IIVs), LAIV and natural infection selectively stimulate mucosal immunity. Developments in mucosal immunology now enable measurement of diverse aspects of mucosal immunity, including the frequencies and functions of nasal antibodies, T cells, and B cells. This review assesses the potential of new sampling and assay approaches that may overcome inconsistent findings from previous methodologies. Standardization of the collection and assessment of mucosal samples is essential in developing new CoPs for vaccine development and licensure of novel vaccines that induce nasal protection and are more effective in prevention of viral transmission.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100381"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RUNX2 promotes chromatin accessibility and WNT signaling in inflamed intestinal epithelial cells","authors":"Rodolfo I. Cabrera-Silva,&nbsp;Zachary S. Wilson,&nbsp;Jael Miranda,&nbsp;Shuling Fan,&nbsp;Michael Dame,&nbsp;Shrinivas Bishu,&nbsp;Jason R. Spence,&nbsp;Jennifer C. Brazil,&nbsp;Justin Colacino,&nbsp;Asma Nusrat,&nbsp;Charles A. Parkos","doi":"10.1016/j.mucimm.2026.100361","DOIUrl":"10.1016/j.mucimm.2026.100361","url":null,"abstract":"<div><div>Ulcerative colitis (UC) is characterized by chronic mucosal inflammation, recurrent epithelial injury, and impaired colonic mucosal wound healing. While WNT/β-catenin dysregulation has been reported in UC, the mechanisms of such abnormalities remain unclear. To investigate epithelial intrinsic alterations associated with UC, we performed single-nucleus RNA-seq (snRNA-seq) and ATAC-seq (snATAC-seq) multiomics on human primary colonic epithelial cells (colonoids) from healthy donors and patients with inactive or active UC. Colonoids were cultured in a 3D matrix recapitulating crypt base cells or grown as 2D monolayers in differentiation medium to recapitulate luminal epithelial cells. Colonoids from active UC had a unique cell population with elevated CTNNB1 and reduced APC expression. Chromatin profiling identified enrichment of RUNX2 motifs in this UC-associated cell population. Active UC colonoids exhibited reduced OLFM4 expression in 3D and the differentiation marker VIL1 in 2D, suggesting impaired epithelial stem-cell maintenance and maturation. RUNX2 inhibition using CADD522 reduced β-catenin levels in 3D colonoids and restored VIL1 expression and junctional β-catenin localization in 2D cultures. These findings reveal an intrinsic defect in epithelial renewal in UC, driven in part by RUNX2-dependent WNT dysregulation. Our study identifies RUNX2 as a transcriptional regulator of epithelial stem cell function and WNT signaling in the inflamed human colon.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100361"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148226967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}