Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
Department of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
J Invest Dermatol. 2014 May;134(5):1255-1264. doi: 10.1038/jid.2013.501. Epub 2013 Nov 25.
Topical application of the vitamin D (VitD) analog calcipotriol is a highly effective standard treatment modality of psoriatic skin lesions. However, the immune modulatory effects of the treatment are incompletely understood. VitD is well known to induce tolerogenic responses in conventional dendritic cells (cDCs). Plasmacytoid DCs (pDCs) comprise a specialized, naturally occurring DC subset known to be important in autoimmune diseases including psoriasis. pDCs from the blood rapidly infiltrate psoriatic skin and are key to the initiation of the immune-mediated pathogenesis of the disease. We now demonstrate that pDCs express various proteins of the VitD receptor (VDR) pathway, including the VitD-metabolizing enzymes Cyp27B1 and Cyp24A1, and that VDR is transcriptionally active in pDCs. Moreover, VitD impairs the capacity of murine and human pDCs to induce T-cell proliferation and secretion of the T-helper 1 cytokine IFNγ. The inhibitory effect of VitD is dependent on the expression of the VDR in the DCs. This study demonstrates that VitD signaling can act as a natural inhibitory mechanism on both cDCs and pDCs, which may instigate the development of VitD-based therapeutic applications for psoriasis and other inflammatory skin diseases.
局部应用维生素 D（VitD）类似物卡泊三醇是治疗银屑病皮损的一种非常有效的标准治疗方法。然而，其免疫调节作用尚不完全清楚。众所周知，VitD 可诱导传统树突状细胞（cDC）产生耐受反应。浆细胞样树突状细胞（pDC）是一种特殊的、天然存在的树突状细胞亚群，已知在包括银屑病在内的自身免疫性疾病中具有重要作用。血液中的 pDC 迅速浸润银屑病皮肤，是引发疾病免疫介导发病机制的关键。我们现在证明 pDC 表达 VitD 受体（VDR）途径的各种蛋白，包括 VitD 代谢酶 Cyp27B1 和 Cyp24A1，并且 VDR 在 pDC 中转录活跃。此外，VitD 可损害小鼠和人 pDC 诱导 T 细胞增殖和 T 辅助 1 细胞因子 IFNγ 分泌的能力。VitD 的抑制作用依赖于 DC 中 VDR 的表达。这项研究表明，VitD 信号可以作为一种天然的抑制机制作用于 cDC 和 pDC，这可能为银屑病和其他炎症性皮肤病的 VitD 治疗应用的发展奠定基础。
