1,25-Dihydroxyvitamin D3 Promotes Tolerogenic Dendritic Cells with Functional Migratory Properties in NOD Mice
1,25-Dihydroxyvitamin D3 Promotes Tolerogenic Dendritic Cells with Functional Migratory Properties in NOD Mice
复制标题
DOI：
10.4049/jimmunol.1302350
复制
发表时间：
2014-05-01
影响因子：
4.4
通讯作者：
Mathieu, Chantal
中科院分区：
文献类型：
--
作者：
Ferreira, Gabriela B.;Gysemans, Conny A.;Mathieu, Chantal
维生素D的生物活性形式1，25-二羟基维生素D-3 [1，25（OH）（2）D-3]能够促进致耐受性成熟树突状细胞（mDC）的产生，其活化自身反应性T细胞的能力受损。这些细胞可以代表通过疫苗接种策略促进或恢复Ag特异性耐受性的可靠工具，例如在1型糖尿病患者中。然而，1，25（OH）（2）D-3处理的mDC（1，25 D（3）-mDC）的成功转移取决于1，25（OH）（2）D-3在来自糖尿病易感供体的细胞中与来自糖尿病抗性供体的细胞中印记类似的致耐受性谱的能力。在这项研究中，我们研究了1，25（OH）（2）D-3对来自健康（C57 BL/6）和糖尿病易感（NOD）小鼠的mDC的功能和表型的影响。我们表明，1，25（OH）（2）D-3能够在两种小鼠品系来源的DC上印记表型致耐受性谱。NOD和C57 BL/6来源的1，25 D（3）-mDC在体外均降低自身反应性T细胞的增殖和活化，尽管在细胞因子/趋化因子表达的调节方面存在品系差异。此外，来自糖尿病易感小鼠的1，25 D（3）-mDC扩增了CD 25（+）Foxp 3（+）调节性T细胞，并在体外诱导T细胞产生细胞内IL-10。此外，1，25 D（3）-mDCs在体内表现出完整的功能迁移能力，有利于归巢到成年NOD小鼠的肝脏和胰腺。更重要的是，当与活化的CD 4（+）T细胞共转移到NOD.SCID受体中时，1，25 D（3）-mDC有效地抑制了胰腺引流淋巴结中自身反应性供体T细胞的增殖。总之，这些结果证明了1，25 D（3）-mDCs在体内恢复Ag特异性免疫耐受和阻止自身免疫性疾病进展的潜力。
The biologically active form of vitamin D, 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3], is able to promote the generation of tolerogenic mature dendritic cells (mDCs) with an impaired ability to activate autoreactive T cells. These cells could represent a reliable tool for the promotion or restoration of Ag-specific tolerance through vaccination strategies, for example in type 1 diabetes patients. However, successful transfer of 1,25(OH)(2)D-3-treated mDCs (1,25D(3)-mDCs) depends on the capacity of 1,25(OH)(2)D-3 to imprint a similar tolerogenic profile in cells derived from diabetes-prone donors as from diabetes-resistant donors. In this study, we examined the impact of 1,25(OH)(2)D-3 on the function and phenotype of mDCs originating from healthy (C57BL/6) and diabetes-prone (NOD) mice. We show that 1,25(OH)(2)D-3 is able to imprint a phenotypic tolerogenic profile on DCs derived from both mouse strains. Both NOD- and C57BL/6-derived 1,25D(3)-mDCs decreased the proliferation and activation of autoreactive T cells in vitro, despite strain differences in the regulation of cytokine/chemokine expression. In addition, 1,25D(3)-mDCs from diabetes-prone mice expanded CD25(+)Foxp3(+) regulatory T cells and induced intracellular IL-10 production by T cells in vitro. Furthermore, 1,25D(3)-mDCs exhibited an intact functional migratory capacity in vivo that favors homing to the liver and pancreas of adult NOD mice. More importantly, when cotransferred with activated CD4(+) T cells into NOD.SCID recipients, 1,25D(3)-mDCs potently dampened the proliferation of autoreactive donor T cells in the pancreatic draining lymph nodes. Altogether, these results argue for the potential of 1,25D(3)-mDCs to restore Ag-specific immune tolerance and arrest autoimmune disease progression in vivo.