{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:45:23Z","timestamp":1785908723886,"version":"3.56.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC) and psoriasis (PsO) are two common immune-mediated inflammatory diseases with significant comorbidity, yet whether one directly causes the other or they share common genetic and immunopathological backgrounds remains unclear. This study integrated bioinformatics, animal experiments, and bidirectional Mendelian randomization to systematically identify potential common molecular targets mediating the comorbidity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptomic data for UC and PsO were obtained from the Gene Expression Omnibus (GEO) database. Differential expression genes (DEGs) and WGCNA were performed to identify common transcriptomic alterations. Then, machine learning algorithms (SVM, RF, XGBoost, GLM) were used to screen for shared signature genes. The nomogram diagnostic models were constructed, and immune infiltration landscape were analyzed. An acute UC-PsO comorbidity mouse model was established by simultaneous administration of dextran sulfate sodium and imiquimod, and the expression levels of key genes were examined. Finally, bidirectional Mendelian randomization (MR) was performed to assess the genetic causal relationship between UC and PsO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>3,840 DEGs in UC and 4,208 in PsO, with 619 overlapping DEGs, were identified. WGCNA further screened 17 up\u2212regulated and 16 down\u2212regulated co\u2212expressed genes common to both diseases. Cross\u2212validation using four machine learning algorithms finally identified CLDN8 and ABCA12 as the core signature genes shared by UC and PsO. Diagnostic models based on these two genes performed well for both diseases (specific AUC values can be added). Immune infiltration analysis revealed similar inflammatory pathway characteristics between the two diseases. In the UC\u2212PsO comorbidity animal model, the expression changes of CLDN8 and ABCA12 were consistent with those in clinical samples, confirming their functional relevance. Bidirectional MR analysis showed no significant causal effect of UC on PsO nor of PsO on UC, which does not support the direct causation hypothesis but instead supports the shared mechanism hypothesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CLDN8 and ABCA12 shared molecular signature in UC-PsO comorbidity, however, no direct genetic causal relationship between UC and PsO. Clinically, each disease should be managed according to its own pathology, while targeting common inflammatory pathways involving CLDN8\/ABCA12 to enable personalized treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1862149","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:53:34Z","timestamp":1785905614000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CLDN8 and ABCA12 define a shared molecular signature in ulcerative colitis-psoriasis comorbidity"],"prefix":"10.3389","volume":"17","author":[{"given":"Han","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology","place":["Xianning, China"]},{"name":"Hubei Key Laboratory of Environmental Risks and Related Diseases Precision Control, School of Basic Medicine Sciences, Xianning Medical College, Hubei University of Science and Technology","place":["Xianning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Jin","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Environmental Risks and Related Diseases Precision Control, School of Basic Medicine Sciences, Xianning Medical College, Hubei University of Science and Technology","place":["Xianning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Xianning Medical College, Hubei University of Science and Technology","place":["Xianning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Ruan","sequence":"additional","affiliation":[{"name":"National Demonstration Center for Experimental General Medicine Education, Xianning Medical College, Hubei University of Science and Technology","place":["Xianning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqin","family":"Zhu","sequence":"additional","affiliation":[{"name":"National Demonstration Center for Experimental General Medicine Education, Xianning Medical College, Hubei University of Science and Technology","place":["Xianning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Environmental Risks and Related Diseases Precision Control, School of Basic Medicine Sciences, Xianning Medical College, Hubei University of Science and Technology","place":["Xianning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41572-020-0205-x","article-title":"Ulcerative colitis","volume":"6","author":"Kobayashi","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative colitis","volume":"402","author":"Le Berre","year":"2023","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/s40257-022-00689-w","article-title":"Cutaneous manifestations of inflammatory bowel disease: a basic overview","volume":"23","author":"Pagani","year":"2022","journal-title":"Am J Clin Dermatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252011126","article-title":"Neutrophil extracellular traps in pediatric inflammatory bowel disease: A potential role in ulcerative colitis","volume":"25","author":"Shukrun","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjz152","article-title":"Global prevalence and bidirectional association between psoriasis and inflammatory bowel disease-a systematic review and meta-analysis","volume":"14","author":"Alinaghi","year":"2020","journal-title":"J Crohns Colitis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1241954","article-title":"Risk of herpes zoster associated with JAK inhibitors in immune-mediated inflammatory diseases: a systematic review and network meta-analysis","volume":"14","author":"Xu","year":"2023","journal-title":"Front Pharmacol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4103\/ijdvl.IJDVL_875_17","article-title":"Psoriasis increases the risk of concurrent inflammatory bowel disease: A population-based nationwide study in Korea","volume":"85","author":"Lee","year":"2019","journal-title":"Indian J Dermatol Venereol Leprol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13102334","article-title":"Psoriasis as a potential risk factor for inflammatory bowel disease: Findings from a nationally representative korean population","volume":"13","author":"Kang","year":"2025","journal-title":"Biomedicines"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.07.029","article-title":"Incidence and risk of inflammatory bowel disease in patients with psoriasis-a nationwide 20-year cohort study","volume":"139","author":"Egeberg","year":"2019","journal-title":"J Invest Dermatol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.14309\/ajg.0000000000003673","article-title":"Inflammatory bowel disease and risk of more than 1,500 comorbidities: A disease-wide prediagnostic and postdiagnostic phenomic association study","volume":"121","author":"Ebert","year":"2025","journal-title":"Am J Gastroenterol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.14528","article-title":"Association between psoriasis and inflammatory bowel disease: a danish nationwide cohort study","volume":"175","author":"Egeberg","year":"2016","journal-title":"Br J Dermatol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.jaad.2020.05.089","article-title":"Axial psoriatic arthritis: An update for dermatologists","volume":"84","author":"Gottlieb","year":"2021","journal-title":"J Am Acad Dermatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2025.103839","article-title":"Advances in precision medicine in imaging and therapeutic strategies for psoriatic disease","volume":"24","author":"Witte","year":"2025","journal-title":"Autoimmun Rev"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.993057","article-title":"Adverse events associated with anti-IL-17 agents for psoriasis and psoriatic arthritis: a systematic scoping review","volume":"14","author":"Wang","year":"2023","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.15727","article-title":"Psoriasis: Recent progress in molecular-targeted therapies","volume":"48","author":"Honma","year":"2021","journal-title":"J Dermatol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1422626","article-title":"Causal associations between both psoriasis and psoriatic arthritis and multiple autoimmune diseases: a bidirectional two-sample mendelian randomization study","volume":"15","author":"Duan","year":"2024","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1007\/s00403-024-03617-6","article-title":"Bioinformatics analysis reveals potential crosstalk genes and molecular mechanisms between ulcerative colitis and psoriasis","volume":"317","author":"Luo","year":"2024","journal-title":"Arch Dermatol Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1177\/17562848241227037","article-title":"The association between psoriasis, psoriasis severity, and inflammatory bowel disease: a population-based analysis","volume":"17","author":"Shani","year":"2024","journal-title":"Ther Adv Gastroenterol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000044022","article-title":"Chemotaxis-related molecular markers underlying the immune disorder of psoriasis and ulcerative colitis: Preliminary analysis and verification","volume":"104","author":"Zhang","year":"2025","journal-title":"Med (Baltimore)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/srt.13574","article-title":"Identification of potential crucial genes shared in psoriasis and ulcerative colitis by machine learning and integrated bioinformatics","volume":"30","author":"Zhang","year":"2024","journal-title":"Skin Res Technol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e37624","article-title":"Exploring shared mechanisms between ulcerative colitis and psoriasis and predicting therapeutic natural compounds through bioinformatics and molecular docking","volume":"10","author":"Yang","year":"2024","journal-title":"Heliyon"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-023-00561-6","article-title":"Weighted gene co-expression network analysis for hub genes in colorectal cancer","volume":"76","author":"Xu","year":"2024","journal-title":"Pharmacol Rep"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1545185","article-title":"Comprehensive analysis of immunogenic cell death-related genes in liver ischemia-reperfusion injury","volume":"16","author":"Lu","year":"2025","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1177\/11769343211009898","article-title":"Weighted gene co-expression network analysis of hub genes in lung adenocarcinoma","volume":"17","author":"Luo","year":"2021","journal-title":"Evol Bioinform Online"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26125590","article-title":"XGB-BIF: An XGBoost-driven biomarker identification framework for detecting cancer using human genomic data","volume":"26","author":"Ghuriani","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154052","article-title":"Huangqin decoction ameliorates DSS-induced ulcerative colitis: Role of gut microbiota and amino acid metabolism, mTOR pathway and intestinal epithelial barrier","volume":"100","author":"Li","year":"2022","journal-title":"Phytomedicine"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111191","article-title":"Dysbiosis in imiquimod-induced psoriasis alters gut immunity and exacerbates colitis development","volume":"40","author":"Pinget","year":"2022","journal-title":"Cell Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.156508","article-title":"Jieyu Guben decoction alleviates combined allergic rhinitis and asthma syndrome by balancing Th17\/Treg expression and restoring PPARD","volume":"139","author":"He","year":"2025","journal-title":"Phytomedicine"},{"key":"B29","doi-asserted-by":"publisher","first-page":"15.25.1","DOI":"10.1002\/0471142735.im1525s104","article-title":"Dextran sulfate sodium (DSS)-induced colitis in mice","volume":"104","author":"Chassaing","year":"2014","journal-title":"Curr Protoc Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/nu12072156","article-title":"Efficacy of dietary supplements in inflammatory bowel disease and related autoimmune diseases","volume":"12","author":"Jadhav","year":"2020","journal-title":"Nutrients"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.737256","article-title":"Managing psoriatic arthritis with inflammatory bowel disease and\/or uveitis","volume":"8","author":"Chia","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"19740","DOI":"10.1038\/s41598-022-22465-w","article-title":"A shared tissue transcriptome signature and pathways in psoriasis and ulcerative colitis","volume":"12","author":"Xi","year":"2022","journal-title":"Sci Rep"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/dth.15151","article-title":"New onset inflammatory bowel disease in patient treated with secukinumab: Case report and review of literature","volume":"34","author":"Ali","year":"2021","journal-title":"Dermatol Ther"},{"key":"B34","doi-asserted-by":"publisher","first-page":"18525","DOI":"10.1038\/s41598-025-03833-8","article-title":"Novel ribosome biogenesis-related biomarkers and therapeutic targets identified in psoriasis","volume":"15","author":"Liu","year":"2025","journal-title":"Sci Rep"},{"key":"B35","doi-asserted-by":"publisher","first-page":"6039","DOI":"10.1038\/s41598-023-33292-y","article-title":"Identification of hub genes and immune infiltration in ulcerative colitis using bioinformatics","volume":"13","author":"Hu","year":"2023","journal-title":"Sci Rep"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btad415","article-title":"PyWGCNA: a Python package for weighted gene co-expression network analysis","volume":"39","author":"Rezaie","year":"2023","journal-title":"Bioinformatics"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.22958","article-title":"Bioinformatics analysis reveals transcriptome and microRNA signatures and drug repositioning targets for IBD and other autoimmune diseases","volume":"18","author":"Clark","year":"2012","journal-title":"Inflammation Bowel Dis"},{"key":"B38","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/s41392-024-01757-9","article-title":"NF-\u03baB in biology and targeted therapy: new insights and translational implications","volume":"9","author":"Guo","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B39","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s13059-016-0901-8","article-title":"Pro-inflammatory miR-223 mediates the cross-talk between the IL23 pathway and the intestinal barrier in inflammatory bowel disease","volume":"17","author":"Wang","year":"2016","journal-title":"Genome Biol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2025.1387128","article-title":"Effects of Th1\/Th17 and Th2 cytokines on lipid metabolism in differentiated keratinocytes","volume":"16","author":"Cavallo","year":"2025","journal-title":"Front Physiol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1597528","article-title":"Multi-omics reveals efferocytosis-related hub genes as biomarkers for ustekinumab response in colitis","volume":"16","author":"Wang","year":"2025","journal-title":"Front Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-024-03053-y","article-title":"Predicting asthma exacerbations using machine learning models","volume":"42","author":"Turcatel","year":"2025","journal-title":"Adv Ther"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/frai.2022.963781","article-title":"Frost prediction using machine learning and deep neural network models","volume":"5","author":"Talsma","year":"2023","journal-title":"Front Artif Intell"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0330175","article-title":"On nonparametric estimating ROC curve based on non-uniform rational B-spline","volume":"20","author":"Erdo\u011fan","year":"2025","journal-title":"PloS One"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/jalm\/jfae125","article-title":"Non-HDL cholesterol may be preferred over apolipoprotein B-100 for risk assessment when evaluated by receiver operator characteristic curve analysis","volume":"10","author":"Levinson","year":"2025","journal-title":"J Appl Lab Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.patter.2024.100994","article-title":"The receiver operating characteristic curve accurately assesses imbalanced datasets","volume":"5","author":"Richardson","year":"2024","journal-title":"Patterns (N Y)"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.07.042","article-title":"Extraintestinal manifestations of inflammatory bowel disease: Current concepts, treatment, and implications for disease management","volume":"161","author":"Rogler","year":"2024","journal-title":"Gastroenterology"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054901","article-title":"Psoriatic arthritis: Pathogenesis and targeted therapies","volume":"24","author":"Azuaga","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1234535","article-title":"Cutaneous manifestations of inflammatory bowel disease: basic characteristics, therapy, and potential pathophysiological associations","volume":"14","author":"He","year":"2023","journal-title":"Front Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700944","article-title":"PPAR and LXR activators regulate ABCA12 expression in human keratinocytes","volume":"128","author":"Jiang","year":"2008","journal-title":"J Invest Dermatol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.51","article-title":"The unfolded protein response is activated in differentiating epidermal keratinocytes","volume":"129","author":"Sugiura","year":"2009","journal-title":"J Invest Dermatol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2020.08.010","article-title":"Acute skin barrier disruption alters the secretion of lamellar bodies via the multilayered expression of ABCA12","volume":"100","author":"Teramura","year":"2020","journal-title":"J Dermatol Sci"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1862149\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:53:37Z","timestamp":1785905617000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1862149\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":52,"alternative-id":["10.3389\/fimmu.2026.1862149"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1862149","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]},"article-number":"1862149"}}