Human T lymphocytes are direct targets of 1,25-dihydroxyvitamin D3 in the immune system

• DOI: 10.1016/j.jsbmb.2010.03.037
• Publication Date: 2010-03-18T08:33:34Z
• Authors: Femke Baeke; Hannelie Korf; Lut Overbergh; Evelyne van Etten; Annemieke Verstuyf; Conny Gysemans; Chantal Mathieu
• Keywords: 0303 health sciences; CD3 Complex; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes; Flow Cytometry; Models, Biological; 3. Good health; Kinetics; 03 medical and health sciences; Calcitriol; Immune System; Cytokines; Humans; Receptors, Calcitriol; Vitamin D; Cells, Cultured; Signal Transduction

Besides its actions on minerals and bone, the bioactive vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has important immunomodulatory properties. Within the immune system, dendritic cells represent key targets for this hormone and 1,25(OH)2D3-induced changes in their phenotype and function ultimately affects T lymphocytes. However, the presence of vitamin D receptors (VDR) in activated T cells proposes additional mechanisms for 1,25(OH)2D3 to directly regulate T cell responses. Here, we investigated the expression and kinetics of vitamin D-related genes in human activated T lymphocytes. Different activation stimuli elicited increased VDR- and 1-alpha-hydroxylase expression, with a highly similar kinetic pattern. Addition of 1,25(OH)2D3 effectively triggered VDR signaling, as evidenced by 24-hydroxylase induction, but only when introduced to T lymphocytes expressing high levels of VDR. This enhanced degree of VDR signaling correlated with a stronger inhibition of cytokines (IFN-gamma, IL-10) and modulation of homing receptor expression (CCR10, CLA) in long-term T cell cultures. Importantly, chronic 1,25(OH)2D3-exposure further amplified VDR signaling and the concomitant T cell modulating effects. In conclusion, we validate T cells as direct targets for 1,25(OH)2D3 and provide this optimized in vitro model to improve our understanding of the role of vitamin D as a direct regulator of T cell responses.