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

• Published in: Frontiers in immunology Vol. 12; p. 722806
• Main Authors: Lopez, Daniel Villalba, Al-Jaberi, Fatima A. H., Woetmann, Anders, Ødum, Niels, Bonefeld, Charlotte Menné, Kongsbak-Wismann, Martin, Geisler, Carsten
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 21.09.2021
• Subjects: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - metabolism; Biological Availability; cytokines; DBP; Humans; Immunology; macrophages; Macrophages - metabolism; T cells; T-Lymphocytes, Regulatory - metabolism; Vitamin D; Vitamin D - metabolism; Vitamin D-Binding Protein - metabolism; macrophages; cytokines; DBP; Vitamin D; T cells
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.722806

The active form of vitamin D 3 (1,25(OH) 2 D 3 ) has a great impact on T cell effector function. Thus, 1,25(OH) 2 D 3 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) 2 D 3 and the precursor 25(OH)D 3 , 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 3 into 1,25(OH) 2 D 3 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 3 by DBP and to produce sufficient levels of 1,25(OH) 2 D 3 to affect T cell effector function. This study suggests that in highly inflammatory conditions, M1 macrophages can produce sufficient levels of 1,25(OH) 2 D 3 to modify T cell responses and thereby reduce T cell-mediated inflammation via a vitamin D-mediated negative feed-back loop.