{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T16:42:40Z","timestamp":1793032960497,"version":"4.5.0"},"reference-count":198,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"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:p>\n                    Vitamin D\n                    <jats:sub>3<\/jats:sub>\n                    (VitD\n                    <jats:sub>3<\/jats:sub>\n                    ) deficiency affects over one billion individuals globally, representing a critical modifiable risk factor for immune-mediated diseases. Beyond its classical role in calcium metabolism, Vitamin D\n                    <jats:sub>3<\/jats:sub>\n                    orchestrates immune homeostasis through vitamin D receptor (VDR) signaling, exerting profound regulatory effects on both innate and adaptive immunity. Mechanistically, Vitamin D\n                    <jats:sub>3<\/jats:sub>\n                    maintains the balance between antimicrobial defense and inflammatory suppression by inhibiting key pro-inflammatory pathways including nuclear factor \u03baB (NF-\u03baB) and the NOD-like receptor protein 3 (NLRP3) inflammasome, while activating the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)-mediated antioxidant defense system. However, the immunomodulatory effects of Vitamin D\n                    <jats:sub>3<\/jats:sub>\n                    exhibit significant inter-individual variability, with clinical efficacy highly dependent on patient-specific factors including serum 25-hydroxyvitamin D [25(OH)D, calcifediol] levels and\n                    <jats:italic>VDR<\/jats:italic>\n                    gene polymorphisms, driving a paradigm shift from empirical supplementation toward biomarker-guided precision medicine. Novel delivery systems\u2014nanoemulsions, twin-screw extrusion technology, and liposomes\u2014effectively overcome bioavailability and stability limitations of traditional preparations. This review systematically examines the immunomodulatory mechanisms of Vitamin D\n                    <jats:sub>3<\/jats:sub>\n                    , evaluates clinical translation evidence in psoriasis, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), inflammatory bowel disease (IBD), and discusses precision medicine strategies and therapeutic potential.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1770141","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T05:21:16Z","timestamp":1772428876000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Vitamin D3 as an immunomodulatory agent: molecular mechanisms, clinical translation, and precision therapeutic strategies"],"prefix":"10.3389","volume":"17","author":[{"given":"Qing","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"New Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"100032","DOI":"10.1016\/j.pharmr.2024.100032","article-title":"Vitamin D and its analogs in immune 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