AUTHOR=Lopez Daniel Villalba , Al-Jaberi Fatima A. H. , Woetmann Anders , Ødum Niels , Bonefeld Charlotte Menné , Kongsbak-Wismann Martin , Geisler Carsten 

TITLE=Macrophages Control the Bioavailability of Vitamin D and Vitamin D-Regulated T Cell Responses

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.722806

DOI=10.3389/fimmu.2021.722806

ISSN=1664-3224

ABSTRACT=<p>The active form of vitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>) has a great impact on T cell effector function. Thus, 1,25(OH)<sub>2</sub>D<sub>3</sub> promotes T helper 2 (Th2) and regulatory T (Treg) cell function and concomitantly inhibits Th1 and Th17 cell function. Thus, it is believed that vitamin D exerts anti-inflammatory effects. However, vitamin D binding protein (DBP) strongly binds both 1,25(OH)<sub>2</sub>D<sub>3</sub> and the precursor 25(OH)D<sub>3</sub>, leaving only a minor fraction of vitamin D in the free, bioavailable form. Accordingly, DBP in physiological concentrations would be expected to block the effect of vitamin D on T cells and dendritic cells. In the present study, we show that pro-inflammatory, monocyte-derived M1 macrophages express very high levels of the 25(OH)D-1α-hydroxylase CYP27B1 that enables them to convert 25(OH)D<sub>3</sub> into 1,25(OH)<sub>2</sub>D<sub>3</sub> even in the presence of physiological concentrations of DBP. Co-cultivation of M1 macrophages with T cells allows them to overcome the sequestering of 25(OH)D<sub>3</sub> by DBP and to produce sufficient levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> to affect T cell effector function. This study suggests that in highly inflammatory conditions, M1 macrophages can produce sufficient levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> to modify T cell responses and thereby reduce T cell-mediated inflammation <italic>via</italic> a vitamin D-mediated negative feed-back loop.</p>