Vitamin D increases programmed death receptor-1 expression in Crohn's disease

Oncotarget. 2017 Apr 11;8(15):24177-24186. doi: 10.18632/oncotarget.15489.

Abstract

Background: Vitamin D modulates inflammation in Crohn's disease (CD). Programmed death (PD)-1 receptor contributes to the maintenance of immune tolerance. Vitamin D might modulate PD-1 signalling in CD.

Aim: To investigate PD-1 expression on T cell subsets in CD patients treated with vitamin D or placebo.

Methods: We included 40 CD patients who received 1200 IU vitamin D3 for 26 weeks or placebo and eight healthy controls. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated at baseline and week 26. The expressions of PD-1, PD-L1, and surface activation markers were analysed by flow cytometry. Soluble PD-1 plasma levels were measured by ELISA.

Results: PD-1 expression upon T cell stimulation was increased in CD4+CD25+int T cells in vitamin D treated CD patients from 19% (range 10 - 39%) to 29% (11 - 79%)(p = 0.03) compared with placebo-treated patients. Vitamin D treatment, but not placebo, decreased the expression of the T cell activation marker CD69 from 42% (31 - 62%) to 33% (19 - 54%)(p = 0.01). Soluble PD-1 levels were not influenced by vitamin D treatment.

Conclusions: Vitamin D treatment increases CD4+CD25+int T cells ability to up-regulate PD-1 in response to activation and reduces the CD69 expression in CD patients.

Keywords: Crohn’s disease; Immune response; Immunity; Immunology and Microbiology Section; PD-1; T cells; vitamin D.

MeSH terms

  • Adult
  • Aged
  • Cells, Cultured
  • Crohn Disease / drug therapy
  • Crohn Disease / genetics*
  • Crohn Disease / immunology
  • Crohn Disease / metabolism*
  • Female
  • Gene Expression Regulation* / drug effects
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / genetics*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Vitamin D / metabolism*
  • Vitamin D / pharmacology
  • Vitamin D / therapeutic use
  • Young Adult

Substances

  • Programmed Cell Death 1 Receptor
  • Vitamin D