1,25-dihydroxyvitamin D3 selectively modulates tolerogenic properties in myeloid but not plasmacytoid dendritic cells
1,25-dihydroxyvitamin D3 selectively modulates tolerogenic properties in myeloid but not plasmacytoid dendritic cells
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DOI：
10.4049/jimmunol.178.1.145
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Adorini, Luciano
中科院分区：
文献类型：
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作者：
Penna, Giuseppe;Amuchastegui, Susana;Adorini, Luciano
1,25-DiHydroxyvitamin D-3 (1,25(OH)(2)A(3)) 是一种免疫调节剂，可诱导树突状细胞 (DC) 产生耐受性。为了进一步了解其作用机制，我们研究了 1,25(OH)(2)D-3 对血髓样 (M-Ms) 和浆细胞样 (P-Ms) 人类 DC 亚群耐受特性的影响。 M-DC 暴露于 1,25(OH)(2)D-3 会上调 CCL22（一种吸引调节性 T 细胞的趋化因子）的产生，而 CCL17（另一种 CCR4 配体）的产生则减少。正如预期的那样，1,25(OH)2D3 还减少了 M-DC 产生的 IL-12p75，并抑制了 CCR7 的表达。 1,25(OH)2D3处理显着增加CD4(+)抑制性T细胞活性，同时降低M-DC诱导Th1细胞发育的能力。令人惊讶的是，1,25(OH)(2)D-3 对 P-DC 的耐受性没有产生任何明显的影响，甚至它们的 IFN-α 的高产量也没有受到调节。特别是，P-DC 诱导 CD4(+) 抑制性 T 细胞的内在高能力不受 1,25(OH)(2)D-3 的影响。两个 DC 亚群表达相似水平的维生素 D 受体，并且其与 1,25(OH)(2)D-3 的连接类似地激活初级反应基因 cyp24。有趣的是，1,25(OH)(2)D-3 抑制 M-DC 中的 NF-kappa B p65 磷酸化和核转位，但不抑制 P-DC，这表明 1,25(OH)(2)D-3 无法调节 P-DC 中的耐受性特性。
1,25-Dihydroxyvitamin D-3 (1,25(OH)(2)A(3)) is an immunomodulatory agent inducing dendritic cells (DCs) to become tolerogenic. To further understand its mechanisms of action, we have examined the effects of 1,25(OH)(2)D-3 on tolerogenic properties of blood myeloid (M-Ms) and plasmacytoid (P-Ms) human DC subsets. Exposure of M-DCs to 1,25(OH)(2)D-3 up-regulated production of CCL22, a chemokine attracting regulatory T cells, whereas production of CCL17, the other CCR4 ligand, was reduced. 1,25(OH)2D3 also decreased IL-12p75 production by M-DCs, as expected, and inhibited CCR7 expression. 1,25(OH)2D3 treatment markedly increased CD4(+) suppressor T cell activity while decreasing the capacity of M-DCs to induce Th1 cell development. Surprisingly, 1,25(OH)(2)D-3 did not exert any discernible effect on tolerogenic properties of P-DCs, and even their high production of IFN-alpha was not modulated. In particular, the intrinsically high capacity of P-DCs to induce CD4(+) suppressor T cells was unaffected by 1,25(OH)(2)D-3 Both DC subsets expressed similar levels of the vitamin D receptor, and its ligation by 1,25(OH)(2)D-3 similarly activated the primary response gene cyp24. Interestingly, 1,25(OH)(2)D-3 inhibited NF-kappa B p65 phosphorylation and nuclear translocation in M-DCs but not P-DCs, suggesting a mechanism for the inability of 1,25(OH)(2)D-3 to modulate tolerogenic properties in P-DCs.