In:
European Journal of Immunology, Wiley, Vol. 44, No. 6 ( 2014-06), p. 1781-1790
Abstract:
The active vitamin D metabolite 1α,25‐dihydroxyvitamin D (1,25[ OH ] 2 D ) potently inhibits DC priming of T ‐cell activation, suggesting that it mediates a homeostatic role in this context. Therefore, careful regulation of 1,25[ OH ] 2 D levels is necessary to avoid inappropriate inhibition of T ‐cell activation. Cell‐autonomous control of vitamin D activity can be modulated by the action of the vitamin D ‐activating and ‐inactivating hydroxylases, CYP 27 B 1, and CYP 24 A 1, respectively. We show that in comparison to macrophages, human monocyte‐derived DC s exhibit significantly less activation of 25‐dihydroxyvitamin D to 1,25[ OH ] 2 D , and that DC s predominantly express a truncated CYP 27 B 1 transcript that may contribute to the deficiency in activation of vitamin D . Furthermore, in response to stimulation with 1,25[ OH ] 2 D , upregulation of the inactivating enzyme CYP 24 A 1 curtailed the functional effects of vitamin D in DC s, but not macrophages. Production of 1,25[ OH ] 2 D by macrophages was adequate to induce expression of vitamin D ‐responsive genes by DC s, inhibit DC maturation in response to innate immune stimulation and DC ‐dependent T ‐cell responses. Our data suggest that in comparison to macrophages, differential regulation of hydroxylases limits autocrine vitamin D activity in DC s, and that paracrine activation of vitamin D exerts a more potent mechanism for homeostatic control of DC function.
Type of Medium:
Online Resource
ISSN:
0014-2980
,
1521-4141
DOI:
10.1002/eji.201344157
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
1491907-2
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