Macrophages Control the Bioavailability of Vitamin D and Vitamin D-Regulated T Cell Responses
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Macrophages Control the Bioavailability of Vitamin D and Vitamin D-Regulated T Cell Responses. / Lopez, Daniel Villalba; Al-Jaberi, Fatima A.H.; Woetmann, Anders; Ødum, Niels; Bonefeld, Charlotte Menné; Kongsbak-Wismann, Martin; Geisler, Carsten.
In: Frontiers in Immunology, Vol. 12, 722806, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Macrophages Control the Bioavailability of Vitamin D and Vitamin D-Regulated T Cell Responses
AU - Lopez, Daniel Villalba
AU - Al-Jaberi, Fatima A.H.
AU - Woetmann, Anders
AU - Ødum, Niels
AU - Bonefeld, Charlotte Menné
AU - Kongsbak-Wismann, Martin
AU - Geisler, Carsten
N1 - Publisher Copyright: © Copyright © 2021 Lopez, Al-Jaberi, Woetmann, Ødum, Bonefeld, Kongsbak-Wismann and Geisler.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - cytokines
KW - DBP
KW - macrophages
KW - T cells
KW - Vitamin D
U2 - 10.3389/fimmu.2021.722806
DO - 10.3389/fimmu.2021.722806
M3 - Journal article
C2 - 34621269
AN - SCOPUS:85116471467
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 722806
ER -
ID: 284196788