{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:02:03Z","timestamp":1760148123213,"version":"build-2065373602"},"reference-count":76,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FISM\u2014Fondazione Italiana Sclerosi Multipla","award":["2009\/R\/12"],"award-info":[{"award-number":["2009\/R\/12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Immune mechanisms play an essential role in driving multiple sclerosis (MS) and altered trafficking and\/or activation of dendritic cells (DC) were observed in the central nervous system and cerebrospinal fluid of MS patients. Interferon \u03b2 (IFN\u03b2) has been used as a first-line therapy in MS for almost three decades and vitamin D deficiency is a recognized environmental risk factor for MS. Both IFN\u03b2 and vitamin D modulate DC functions. Here, we studied the response to 1,25-dihydoxyvitamin D3 (1,25(OH)2D3) of DC obtained with IFN\u03b2\/GM-CSF (IFN-DC) compared to classically derived IL4-DC, in three donor groups: MS patients free of therapy, MS patients undergoing IFN\u03b2 therapy, and healthy donors. Except for a decreased CCL2 secretion by IL4-DC from the MS group, no major defects were observed in the 1,25(OH)2D3 response of either IFN-DC or IL4-DC from MS donors compared to healthy donors. However, the two cell models strongly differed for vitamin D receptor level of expression as well as for basal and 1,25(OH)2D3-induced cytokine\/chemokine secretion. 1,25(OH)2D3 up-modulated IL6, its soluble receptor sIL6R, and CCL5 in IL4-DC, and down-modulated IL10 in IFN-DC. IFN-DC, but not IL4-DC, constitutively secreted high levels of IL8 and of matrix-metalloproteinase-9, both down-modulated by 1,25(OH)2D3. DC may contribute to MS pathogenesis, but also provide an avenue for therapeutic intervention. 1,25(OH)2D3-induced tolerogenic DC are in clinical trial for MS. We show that the protocol of in vitro DC differentiation qualitatively and quantitatively affects secretion of cytokines and chemokines deeply involved in MS pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms24076717","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T04:09:50Z","timestamp":1680581390000},"page":"6717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["1,25(OH)2D3 Differently Modulates the Secretory Activity of IFN-DC and IL4-DC: A Study in Cells from Healthy Donors and MS Patients"],"prefix":"10.3390","volume":"24","author":[{"given":"Isabella","family":"Sanseverino","sequence":"first","affiliation":[{"name":"National Center for Global Health, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arturo Ottavio","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"National Center for Global Health, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Purificato","sequence":"additional","affiliation":[{"name":"National Center for Global Health, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Cortese","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Millefiorini","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cristina","family":"Gauzzi","sequence":"additional","affiliation":[{"name":"National Center for Global Health, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1016\/S0140-6736(18)30481-1","article-title":"Multiple Sclerosis","volume":"391","author":"Thompson","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1097\/WCO.0b013e3283533a7e","article-title":"Vitamin D and Multiple Sclerosis: Epidemiology, Immunology, and Genetics","volume":"25","author":"Simon","year":"2012","journal-title":"Curr. 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