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

// Mia Bendix 1 , Stinne Greisen 2,3 , Anders Dige 1 , Christian L. Hvas 1 , Nina Bak 1 , Søren P. Jørgensen 1 , Jens F. Dahlerup 1 , Bent Deleuran 2,3 and Jørgen Agnholt 1 1 Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark 2 Department of Immunology, Institute of Biomedicine, Aarhus University, Aarhus, Denmark 3 Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark Correspondence to: Mia Bendix, email: // Keywords : PD-1, Crohn’s disease, vitamin D, T cells, Immunology and Microbiology Section, Immune response, Immunity Received : November 18, 2016 Accepted : February 07, 2017 Published : February 18, 2017 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.