Suppressive effect of 1α,25-dihydroxyvitamin D3 on type IIFN-mediated monocyte differentiation into dendritic cells:: Impairment of functional activities and chemotaxis
Suppressive effect of 1α,25-dihydroxyvitamin D3 on type IIFN-mediated monocyte differentiation into dendritic cells:: Impairment of functional activities and chemotaxis
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DOI：
10.4049/jimmunol.174.1.270
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发表时间：
2005-01-01
影响因子：
4.4
通讯作者：
Gessani, S
中科院分区：
文献类型：
--
作者：
Gauzzi, MC;Purificato, C;Gessani, S
Dendritic cells (DCs) generated by a single-step exposure of human monocytes to type I IFN and GM-CSF (IFN-DCs) are endowed with potent immunostimulatory activities and a distinctive migratory response to specific chemokines. In this study, we evaluated the effects of 1alpha,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3), the biologically active metabolite of vitamin D-3, on the DC differentiation/ activation induced by type I IFN. We found that 1,25(OH)(2)D-3 prevented the generation of IFN-DCs when added to freshly isolated monocytes, and was capable of redirecting already differentiated IFN-DCs toward a more immature stage, as revealed by their immunophenotype, reduced allostimulatory activity, and impaired LPS-induced production of Th1-polarizing cytokines. Control and 1,25(OH)(2)D-3-treated IFN-DCs exhibited a similar expression of vitamin D receptor, as well as comparable cell death rates. Furthermore, the chemotactic response of IFN-DCs to CCL4 and CCL19 was markedly reduced or completely abrogated by 1,25(OH)(2)D-3. Despite these changes in the IFN-DC migratory behavior, the expression of CCR5 and CCR7 and the calcium fluxes triggered by CCL4 and CCL19 were not affected. These findings indicate that, in this innovative single-step DC generation model from monocytes, the suppressive effect of 1,25(OH)(2)D-3 is associated with a potent impairment of DC migration in response to inflammatory and lymph node-homing chemokines, thus unraveling a novel mechanism involved in 1,25(OH)(2)D-3-mediated immunomodulation.
