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.
RCT Entities:
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: Ai-Leng Khoo; Irma Joosten; Meta Michels; Rob Woestenenk; Frank Preijers; Xue-Hui He; Mihai G Netea; André J A M van der Ven; Hans J P M Koenen Journal: Immunology Date: 2011-12 Impact factor: 7.397
Authors: Emmanuel Xystrakis; Siddharth Kusumakar; Sandra Boswell; Emma Peek; Zoë Urry; David F Richards; Tonye Adikibi; Carol Pridgeon; Margaret Dallman; Tuck-Kay Loke; Douglas S Robinson; Franck J Barrat; Anne O'Garra; Paul Lavender; Tak H Lee; Christopher Corrigan; Catherine M Hawrylowicz Journal: J Clin Invest Date: 2005-12-08 Impact factor: 14.808
Authors: Joost Smolders; Mariëlle Thewissen; Evelyn Peelen; Paul Menheere; Jan Willem Cohen Tervaert; Jan Damoiseaux; Raymond Hupperts Journal: PLoS One Date: 2009-08-13 Impact factor: 3.240
Authors: Patrick J McCullough; William P McCullough; Douglas Lehrer; Jeffrey B Travers; Steven J Repas Journal: Nutrients Date: 2021-04-29 Impact factor: 5.717