title: Vitamin D reduces the differentiation and expansion of Th17 cells in young asthmatic children.
abstract: Vitamin D [25(OH)D3] deficiency has been associated with asthma as in many inflammatory and autoimmune pathologies; however, there is still a lack of data about the effects of administration of vitamin D in immune regulation in young asthmatic patients. In this study, we investigated its inhibitory effect on the immune response in young asthmatic patients and the possible mechanisms involved. Peripheral blood CD4(+) T cells from 10 asthmatic patients and 10 healthy controls were cultured under Th17 polarizing conditions in the presence or absence of [25(OH)D3], IL-17 cytokine production was determined by ELISA and flow cytometry. Messenger RNA (mRNA) expression of several factors related to Th17 cell function was determined by real-time PCR. The effect of [25(OH)D3]-treated dendritic cells (DCs) on CD4(+) T cell response was determined by ELISA and flow cytometry. Stimulation of naive CD4(+) T cells under Th17 polarizing conditions showed a higher Th17 cell differentiation in asthmatic patients than healthy controls. The addition of [25(OH)D3] significantly inhibited Th17 cell differentiation both in patients [P<0.001] and in normal controls [P=0.001] in a dose-dependent way. [25(OH)D3] was able to inhibit the gene expression of RORC, IL-17, IL-23R, and CCR6. [25(OH)D3]-treated DCs significantly inhibited IL-17 production [P=0.002] and decreased the percentage of CD4(+)IL-17(+) [P=0.007] in young asthmatics. The findings suggest that the inhibitory effect of [25(OH)D3] on the Th17 response was mediated via both T cells and DCs. DCs pathway is involved in the direct inhibition of 25(OH)D3 on Th17 cell differentiation in young asthmatics.
authors.affiliation: Division of Pulmonology, Department of Paediatric Respiratory Diseases, and Research Unit 12SP15, Abderrahman Mami Hospital, Ariana, Tunisia; Tunis El Manar University, Medicine School of Tunis, Division of Histology and Immunology, Department of Basic Sciences, 15 Rue Djebel Lakdar, 1007 Tunis, Tunisia. Electronic address: agnes.hamzaoui@gmail.com.
authors.forename: Agnes
authors.initials: A
authors.lastname: Hamzaoui
authors.affiliation: Division of Pulmonology, Department of Paediatric Respiratory Diseases, and Research Unit 12SP15, Abderrahman Mami Hospital, Ariana, Tunisia; Tunis El Manar University, Medicine School of Tunis, Division of Histology and Immunology, Department of Basic Sciences, 15 Rue Djebel Lakdar, 1007 Tunis, Tunisia. Electronic address: anissa-berraies@hotmail.com.
authors.forename: Anissa
authors.initials: A
authors.lastname: Berraïes
authors.affiliation: Division of Pulmonology, Department of Paediatric Respiratory Diseases, and Research Unit 12SP15, Abderrahman Mami Hospital, Ariana, Tunisia; Tunis El Manar University, Medicine School of Tunis, Division of Histology and Immunology, Department of Basic Sciences, 15 Rue Djebel Lakdar, 1007 Tunis, Tunisia. Electronic address: h_besma@yahoo.fr.
authors.forename: Besma
authors.initials: B
authors.lastname: Hamdi
authors.affiliation: Tunis El Manar University, Medicine School of Tunis, Division of Histology and Immunology, Department of Basic Sciences, 15 Rue Djebel Lakdar, 1007 Tunis, Tunisia. Electronic address: kaabachi.wajih@gmail.com.
authors.forename: Wajih
authors.initials: W
authors.lastname: Kaabachi
authors.affiliation: Division of Pulmonology, Department of Paediatric Respiratory Diseases, and Research Unit 12SP15, Abderrahman Mami Hospital, Ariana, Tunisia; Tunis El Manar University, Medicine School of Tunis, Division of Histology and Immunology, Department of Basic Sciences, 15 Rue Djebel Lakdar, 1007 Tunis, Tunisia. Electronic address: jamelammar2000@yahoo.fr.
authors.forename: Jamel
authors.initials: J
authors.lastname: Ammar
authors.affiliation: Tunis El Manar University, Medicine School of Tunis, Division of Histology and Immunology, Department of Basic Sciences, 15 Rue Djebel Lakdar, 1007 Tunis, Tunisia. Electronic address: kamel.hamzaoui@gmail.com.
authors.forename: Kamel
authors.initials: K
authors.lastname: Hamzaoui
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D002112:Calcifediol / Q000097:blood; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D014807:Vitamin D / Q000097:blood / Q000494:pharmacology*
chemical_list: D014807:Vitamin D; D002112:Calcifediol
keywords: Asthma; CCR6; IL-23R; RORC; Th17; [25(OH)D3]