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The etiology and pathophysiology of psoriasis are still unknown, but the activation of the adaptive immune system with the main role of T-cells is key in psoriasis pathogenesis. The modulation of the local neuroendocrine system with the downregulation of pro-inflammatory and the upregulation of anti-inflammatory messengers represent a promising adjuvant treatment in psoriasis therapies. Vitamin D receptors and vitamin D-mediated signaling pathways function in the skin and are essential in maintaining the skin homeostasis. The active forms of vitamin D act as powerful immunomodulators of clinical response in psoriatic patients and represent the effective and safe adjuvant treatments for psoriasis, even when high doses of vitamin D are administered. The phototherapy of psoriasis, especially UVB-based, changes the serum level of 25(OH)D, but the correlation of 25(OH)D changes and psoriasis improvement need more clinical trials, since contradictory data have been published. Vitamin D derivatives can improve the efficacy of psoriasis phototherapy without inducing adverse side effects. The anti-psoriatic treatment could include non-calcemic CYP11A1-derived vitamin D hydroxyderivatives that would act on the VDR or as inverse agonists on RORs or activate alternative nuclear receptors including AhR and LXRs. In conclusion, vitamin D signaling can play an important role in the natural history of psoriasis. Selective targeting of proper nuclear receptors could represent potential treatment options in psoriasis.<\/jats:p>","DOI":"10.3390\/ijms23158575","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T21:41:37Z","timestamp":1659476497000},"page":"8575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3195-9965","authenticated-orcid":false,"given":"Anna A.","family":"Bro\u017cyna","sequence":"first","affiliation":[{"name":"Department of Human Biology, Institute of Biology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, 87-100 Toru\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radomir M.","family":"Slominski","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Informatics Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6286-0693","authenticated-orcid":false,"given":"Bogus\u0142aw","family":"Nedoszytko","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Allergology and Venerology, Medical University of Gda\u0144sk, 80-211 Gda\u0144sk, Poland"},{"name":"Cytogeneticr Laboratory, Invicta Fertility and Reproductive Centre, 80-850 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2206-3531","authenticated-orcid":false,"given":"Michal A.","family":"Zmijewski","sequence":"additional","affiliation":[{"name":"Department of Histology, Medical University of Gda\u0144sk, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8963-3995","authenticated-orcid":false,"given":"Andrzej T.","family":"Slominski","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Laboratory Service, VA Medical Center at Birmingham, Birmingham,  AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"743180","DOI":"10.3389\/fmed.2021.743180","article-title":"The Global, Regional, and National Burden of Psoriasis: Results and Insights From the Global Burden of Disease 2019 Study","volume":"8","author":"Damiani","year":"2021","journal-title":"Front. 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