{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:59:32Z","timestamp":1791845972011,"version":"4.3.4"},"reference-count":270,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Abiogen Pharma S.p.A, Pisa, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vitamin D is increasingly recognized as a key regulator of epithelial barrier integrity and mucosal immune homeostasis, with implications extending far beyond skeletal health. Through the vitamin D receptor (VDR), vitamin D regulates epithelial cohesion, innate immune responses, and tight-junction gene expression. This review explores the multifactorial role of vitamin D in modulating inflammation and preserving tissue barriers, with particular emphasis on its effects on tight junction (TJ) regulation and disease states characterized by barrier dysfunction, namely atopic dermatitis, psoriasis, inflammatory bowel disease (IBD), and celiac disease. In these settings, vitamin D\/VDR signaling exerts protective actions by enhancing barrier structure, suppressing Th1\/Th17-driven inflammation, modulating the gut and skin microbiome, and promoting epithelial repair. Animal studies and clinical data suggest that vitamin D supplementation can restore TJ expression, reduce disease activity, and improve clinical outcomes in both intestinal and dermatologic diseases. In the cardiovascular system, the role of vitamin D remains complex. While vitamin D influences endothelial function, insulin sensitivity, and systemic inflammation, supplementation trials yield mixed results, indicating a need for individualized approaches. Overall, this review synthesizes mechanistic, translational, and clinical data supporting vitamin D as a crucial modulator of barrier integrity and inflammation. These findings highlight its therapeutic relevance in chronic diseases characterized by immune dysregulation and epithelial disruption.<\/jats:p>","DOI":"10.3390\/ijms26178520","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"8520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Non-Skeletal Roles of Vitamin D in Skin, Gut, and Cardiovascular Disease: Focus on Epithelial Barrier Function and Immune Regulation in Chronic Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7855-6621","authenticated-orcid":false,"given":"Teresa","family":"Grieco","sequence":"first","affiliation":[{"name":"Dermatology Clinic, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Paolino","sequence":"additional","affiliation":[{"name":"Unit of Dermatology and Cosmetology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Moliterni","sequence":"additional","affiliation":[{"name":"Dermatology Clinic, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Chello","sequence":"additional","affiliation":[{"name":"Dermatology Clinic, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Morelli","sequence":"additional","affiliation":[{"name":"Fondazione Pisana per la Scienza, 56017 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Nannipieri","sequence":"additional","affiliation":[{"name":"Clinical Research, Abiogen Pharma, 56121 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9591-1046","authenticated-orcid":false,"given":"Santina","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Clinical Research, Abiogen Pharma, 56121 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Accoto","sequence":"additional","affiliation":[{"name":"Clinical Research, Abiogen Pharma, 56121 Pisa, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Pellacani","sequence":"additional","affiliation":[{"name":"Dermatology Clinic, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Calvieri","sequence":"additional","affiliation":[{"name":"Dermatology Clinic, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D Deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N. 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