title: High-dose cholecalciferol supplementation significantly increases peripheral CD4⁺ Tregs in healthy adults without negatively affecting the frequency of other immune cells.
abstract: BACKGROUND
  Regulatory T cells (Tregs) play a central role in the maintenance of self-tolerance. Animal and in vitro studies suggest that vitamin D is involved in reducing the risk of autoimmunity by modulating Tregs.
  
  
  METHODS
  In a double-blind, placebo controlled study in 60 healthy volunteers, we assessed the effect of a 12-week high-dose oral cholecalciferol supplementation (140,000 IU/month) on the number and function of CD4(pos)CD25(high)FoxP3(pos)CD127(dim) Tregs. We also assessed the clinical safety of the supplementation and the effect on the frequency of other immune cells such as monocytes, dendritic cells, natural killer cells, natural killer T cells, B cells and subgroups of T cells. We also tested the in vitro effect of cholecalciferol on Tregs in human cell cultures.
  
  
  RESULTS
  By using FACS analysis, ex vivo suppressive co-cultures and apoptosis assays, we were able to show that a cholecalciferol supplementation leads to significantly increased numbers of peripheral Tregs in vivo. Tregs function and the frequency of other immune cells remained unchanged, and no clinically relevant safety concerns were found. The in vitro exposure of human peripheral blood mononuclear cells to cholecalciferol also supported our in vivo findings.
  
  
  CONCLUSIONS
  Our results indicate a substantial effect of a supplementation with inactive vitamin D on the immune system of healthy humans in vivo and provide a rationale for future studies to investigate the immunomodulatory effects of vitamin D in autoimmune diseases.
authors.affiliation: Department of Endocrinology and Metabolism, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Prietl
authors.forename: Gerlies
authors.initials: G
authors.lastname: Treiber
authors.forename: Julia K
authors.initials: JK
authors.lastname: Mader
authors.forename: Evelyne
authors.initials: E
authors.lastname: Hoeller
authors.forename: Michael
authors.initials: M
authors.lastname: Wolf
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.forename: Winfried B
authors.initials: WB
authors.lastname: Graninger
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Obermayer-Pietsch
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D000328:Adult; D017209:Apoptosis; D001317:Austria; D001772:Blood Cell Count; D015704:CD4 Antigens / Q000097:blood; D002112:Calcifediol / Q000097:blood; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D018920:Coculture Techniques; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019891:Leukopoiesis; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014808:Vitamin D Deficiency / Q000097:blood / Q000178:diet therapy* / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D002762:Cholecalciferol; D002112:Calcifediol