The role of vitamin D in increasing circulating T regulatory cell numbers and modulating T regulatory cell phenotypes in patients with inflammatory disease or in healthy volunteers: A systematic review

Autoři: Sheila A. Fisher aff001;  Mana Rahimzadeh aff003;  Charlotte Brierley aff004;  Betty Gration aff005;  Carolyn Doree aff001;  Catherine E. Kimber aff001;  Alicia Plaza Cajide aff001;  Abigail A. Lamikanra aff001;  David J. Roberts aff001
Působiště autorů: NHS Blood and Transplant, Oxford, United Kingdom aff001;  Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom aff002;  Oxford University Medical School, John Radcliffe Hospital, Oxford, United Kingdom aff003;  Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford, United Kingdom aff004;  Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom aff005;  Biomedical Research Centre (Haematology Theme), Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, United Kingdom aff006
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222313



The evidence for vitamin D and other agents that experimentally modulate T regulatory cells (Tregs) for the treatment of patients with autoimmune or allergic diseases has not been established.


We have undertaken a systematic review of randomised controlled trials to assess the efficacy of vitamin D, vitamin A, niacin and short-chain fatty acids in enhancing absolute Treg numbers and phenotypes in patients with inflammatory or autoimmune disease.


This systematic review was conducted using a predefined protocol (PROSPERO International prospective register of systematic reviews, ID = CRD42016048648/ CRD42016048646). Randomised controlled trials of patients with inflammatory or autoimmune disease or healthy participants which compared either oral vitamin D or vitamin A or short-chain fatty acids with control or placebo and measured the absolute concentration of proportion of Tregs were eligible for inclusion. Searches of electronic databases (CENTRAL, MEDLINE, EMBASE, CINAHL, PUBMED and Web of Science) identified eight eligible independent trials (seven autoimmune disease trials, one trial of healthy subjects). Data were extracted by two reviewers and the risk of study bias was assessed using Cochrane Collaboration methodology.


Planned meta-analysis was not possible due to the heterogeneous nature of the studies. Nevertheless, in five trials of autoimmune disorders which measured the proportion of Tregs, a higher proportion was observed in the vitamin D group compared to controls at 12 months in all but one trial. In the trial of healthy subjects, a significant difference was reported, with a higher percentage of Tregs observed in the vitamin D group (at 12 weeks, mean 6.4% (SD 0.8%) (vitamin D) vs 5.5% (1.0%) (placebo). There were no trials to assess the efficacy of vitamin A, niacin and short-chain fatty acids in enhancing absolute Treg numbers.


Vitamin D supplementation may increase Treg/CD3 ratios in both healthy individuals and patients with autoimmune disorders and may increase Treg function. There remains a need for further suitably powered clinical studies aimed at enhancing Treg numbers and/or function.

Klíčová slova:

Inflammatory diseases – Regulatory T cells – Systematic reviews – T cells – Vitamins – Oral diseases


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