title: Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis.
abstract: BACKGROUND
  In several autoimmune diseases, including multiple sclerosis (MS), a compromised regulatory T cell (Treg) function is believed to be critically involved in the disease process. In vitro, the biologically active metabolite of vitamin D has been shown to promote Treg development. A poor vitamin D status has been linked with MS incidence and MS disease activity. In the present study, we assess a potential in vivo correlation between vitamin D status and Treg function in relapsing remitting MS (RRMS) patients.
  
  
  RESULTS
  Serum levels of 25-hydroxyvitamin D (25(OH)D) were measured in 29 RRMS patients. The number of circulating Tregs was assessed by flow-cytometry, and their functionality was tested in vitro in a CFSE-based proliferation suppression assay. Additionally, the intracellular cytokine profile of T helper cells was determined directly ex-vivo by flow-cytometry. Serum levels of 25(OH)D correlated positively with the ability of Tregs to suppress T cell proliferation (R = 0.590, P = 0.002). No correlation between 25(OH)D levels and the number of Tregs was found. The IFN-gamma/IL-4 ratio (Th1/Th2-balance) was more directed towards IL-4 in patients with favourable 25(OH)D levels (R = -0.435, P = 0.023).
  
  
  CONCLUSIONS
  These results show an association of high 25(OH)D levels with an improved Treg function, and with skewing of the Th1/Th2 balance towards Th2. These findings suggest that vitamin D is an important promoter of T cell regulation in vivo in MS patients. It is tempting to speculate that our results may not only hold for MS, but also for other autoimmune diseases. Future intervention studies will show whether modulation of vitamin D status results in modulation of the T cell response and subsequent amelioration of disease activity.
authors.affiliation: School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands. j.smolders@mumc.nl
authors.forename: Joost
authors.initials: J
authors.lastname: Smolders
authors.forename: Mariëlle
authors.initials: M
authors.lastname: Thewissen
authors.forename: Evelyn
authors.initials: E
authors.lastname: Peelen
authors.forename: Paul
authors.initials: P
authors.lastname: Menheere
authors.forename: Jan Willem Cohen
authors.initials: JW
authors.lastname: Tervaert
authors.forename: Jan
authors.initials: J
authors.lastname: Damoiseaux
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
mesh_terms: D000328:Adult; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood*
chemical_list: D014807:Vitamin D; D015847:Interleukin-4; D007371:Interferon-gamma; C104450:25-hydroxyvitamin D
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