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Macrophages Control the Bioavailability of Vitamin D and Vitamin D-Regulated T Cell Responses
- Source :
- Lopez, D V, Al-Jaberi, F A H, Woetmann, A, Ødum, N, Bonefeld, C M, Kongsbak-Wismann, M & Geisler, C 2021, ' Macrophages Control the Bioavailability of Vitamin D and Vitamin D-Regulated T Cell Responses ', Frontiers in Immunology, vol. 12, 722806 . https://doi.org/10.3389/fimmu.2021.722806, Frontiers in Immunology, Vol 12 (2021), Frontiers in Immunology
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- The active form of vitamin D3 (1,25(OH)2D3) has a great impact on T cell effector function. Thus, 1,25(OH)2D3 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)2D3 and the precursor 25(OH)D3, 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)D3 into 1,25(OH)2D3 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)D3 by DBP and to produce sufficient levels of 1,25(OH)2D3 to affect T cell effector function. This study suggests that in highly inflammatory conditions, M1 macrophages can produce sufficient levels of 1,25(OH)2D3 to modify T cell responses and thereby reduce T cell-mediated inflammation via a vitamin D-mediated negative feed-back loop.
- Subjects :
- Vitamin
Vitamin D-binding protein
T cell
Immunology
T cells
Biological Availability
Inflammation
T-Lymphocytes, Regulatory
DBP
chemistry.chemical_compound
medicine
Vitamin D and neurology
Humans
Immunology and Allergy
Vitamin D
Original Research
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Chemistry
Effector
Vitamin D-Binding Protein
RC581-607
Molecular biology
cytokines
macrophages
Bioavailability
medicine.anatomical_structure
Immunologic diseases. Allergy
medicine.symptom
Function (biology)
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....45462f47f16694cf5f789eb3ae0a8b06