title: Comparative effect of 25(OH)D3 and 1,25(OH)2D3 on Th17 cell differentiation.
abstract: Vitamin D is a secosteroid hormone that plays an important regulatory role in calcium homeostasis and bone metabolism. Immune cells can both produce and respond to 1,25(OH)2D3. CD4+ T cells from vitamin D receptor (VDR) KO mice produce higher levels of IFN-γ and IL-17 than their wild type counterparts, and play a crucial role in the pathogenesis of autoimmune diseases (AID). We are particularly interested in studying the effect of vitamin D on pathogenic Th17 cells in humans. We investigated the in vitro effect of 1,25(OH)2D3 and 25(OH)D3 on the differentiation and cytokine production of primary CD4+ T cells from normal donors, and cultured in Th17 polarizing conditions. Both forms of vitamin D reduced the expression of pathogenic Th17 markers and their secretion of pro-inflammatory cytokines (IL-17A, IFN-γ). Furthermore, both vitamin D forms induced an expansion of CD25hi cells and upregulated their expression of CTLA-4 and Foxp3 regulatory markers.
authors.affiliation: Department of Experimental Pathology, Microbiology & Immunology, Faculty of Medicine, American University of Beirut, PO Box 11-0236, Beirut, Lebanon.
authors.forename: Lama
authors.initials: L
authors.lastname: Fawaz
authors.affiliation: Nehme and Therese Tohme Multiple Sclerosis Center, Abu Haidar Neuroscience Institute, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: May F
authors.initials: MF
authors.lastname: Mrad
authors.affiliation: Nehme and Therese Tohme Multiple Sclerosis Center, Abu Haidar Neuroscience Institute, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Jalal M
authors.initials: JM
authors.lastname: Kazan
authors.affiliation: Department of Experimental Pathology, Microbiology & Immunology, Faculty of Medicine, American University of Beirut, PO Box 11-0236, Beirut, Lebanon.
authors.forename: Souraya
authors.initials: S
authors.lastname: Sayegh
authors.affiliation: Department of Experimental Pathology, Microbiology & Immunology, Faculty of Medicine, American University of Beirut, PO Box 11-0236, Beirut, Lebanon.
authors.forename: Reem
authors.initials: R
authors.lastname: Akika
authors.affiliation: Nehme and Therese Tohme Multiple Sclerosis Center, Abu Haidar Neuroscience Institute, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon. Electronic address: sk88@aub.edu.lb.
authors.forename: Samia J
authors.initials: SJ
authors.lastname: Khoury
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism; D002112:Calcifediol / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014815:Vitamins / Q000494:pharmacology
chemical_list: D060908:CTLA-4 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D018167:Receptors, Calcitriol; D014815:Vitamins; D016753:Interleukin-10; D007371:Interferon-gamma; D002117:Calcitriol; D002112:Calcifediol
keywords: IL-17A; Th17; Vitamin D