title: CCL2 induction by 1,25(OH)2D3 in dendritic cells from healthy donors and multiple sclerosis patients.
abstract: CCL2 plays a pivotal role in the recruitment of different immune cells to sites of inflammation and evidence indicates its involvement in multiple sclerosis (MS) pathogenesis. MS lesions are characterized by an inflammatory infiltrate, whose nature is controlled by chemokines and cytokines, and elevated expression of CCL2 has been found in acute and chronic MS plaques within the brain. Vitamin D deficiency is currently considered one of the main environmental MS risk factors. In this study we analyzed the role of 1,25(OH)2D3, the bioactive vitamin D metabolite, in the regulation of CCL2 expression by dendritic cells (DC) obtained from healthy donors and relapsing-remitting MS patients. We report that 1,25(OH)2D3, as well as 25OHD3, its main blood precursor, induce the secretion of high levels of CCL2. 1,25(OH)2D3-induced CCL2 levels are comparable to those secreted in response to a classical DC maturation stimulus. Moreover, we observed that 1,25(OH)2D3 is able to induce a significant CCL2 secretion in DC obtained from relapsing-remitting MS patients, although CCL2 levels in these latter are lower with respect to healthy controls. The cause(s) of this apparently defective response of DC from patients and its consequences in the context of MS remain to be elucidated. However, we propose CCL2 as a molecular player contributing to the immunomodulatory activity of 1,25(OH)2D3 on DC, and hypothesize a role for this chemokine in the response of MS patients to vitamin D therapy. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sanseverino
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Arturo O
authors.initials: AO
authors.lastname: Rinaldi
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Purificato
authors.affiliation: Multiple Sclerosis Center, Sapienza University of Rome, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cortese
authors.affiliation: Multiple Sclerosis Center, Sapienza University of Rome, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Millefiorini
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gessani
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy. Electronic address: mariacristina.gauzzi@iss.it.
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Gauzzi
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D002117:Calcitriol / Q000494:pharmacology*; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D012333:RNA, Messenger; D014815:Vitamins; D002117:Calcitriol
keywords: CCL2; Dendritic cell; Multiple sclerosis; Vitamin D