Topically applied 1,25-dihydroxyvitamin D3 enhances the suppressive activity of CD4+CD25+, cells in the draining lymph nodes
Topically applied 1,25-dihydroxyvitamin D3 enhances the suppressive activity of CD4+CD25+, cells in the draining lymph nodes
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DOI：
10.4049/jimmunol.179.9.6273
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发表时间：
2007-11-01
影响因子：
4.4
通讯作者：
Hart, Prue H.
中科院分区：
文献类型：
--
作者：
Gorman, Shelley;Kuritzky, L. Alexandra;Hart, Prue H.
维生素D的免疫调节作用已在小鼠长期口服给药或补充细胞培养物1，25-二羟基维生素D-3（1，25（OH）（2）D-3）1（维生素D的活性形式）后得到描述。在本研究中，局部应用1，25（OH）（2）D-3，增强了引流淋巴结中CD 4（+）CD 25（+）细胞的抑制能力。局部1-25（OH）（2）D-3的作用与UVB照射的作用进行了比较，UVB照射是皮肤中1，25（OH）（2）D-3产生所需的环境因素。来自1，25（OH）（2）D-3处理或UVB照射小鼠的皮肤引流淋巴结（SDLN）的CD 4（+）细胞在体外增殖为Ag的能力降低，并且可以在过继转移到幼稚小鼠后抑制Ag特异性免疫应答。去除CD 4（+）CD 25（+）细胞后，这种调节丧失。此外，在体外和体内试验系统中，从1，25（OH）（2）D-3处理或UVB照射小鼠的SDLN中纯化的CD 4（+）CD 25（+）细胞与来自对照小鼠的相同数量的CD 4（+）CD 25（+）细胞相比，抑制免疫应答的能力增强。在用OVA致敏受体小鼠后，在来自1，25（OH）2D 3处理的小鼠的SDLN的CD 4（+）CD 25（+）细胞的受体中，供体来源的CD 4（+）Foxp 3（+）细胞的比例显著增加，表明这些调节性T细胞可以在抗原刺激下在体内扩增。这些研究表明，1，25（OH）（2）D-3可能是一个重要的介质，其中UVB照射发挥其某些免疫调节作用。
The immunomodulatory effects of vitamin D have been described following chronic oral administration to mice or supplementation of cell cultures with 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3)1 the active form of vitamin D. In this study, topically applied 1,25(OH)(2)D-3, enhanced the suppressive capacity of CD4(+)CD25(+) cells from the draining lymph nodes. The effects of topical 1-25(OH)(2)D-3 were compared with those of UVB irradiation, which is the environmental factor required for 1,25(OH)(2)D-3 production in skin. CD4(+) cells from the skin-draining lymph nodes (SDLN) of either 1,25(OH)(2)D-3-treated or UVB-irradiated mice had reduced capacity to proliferate to Ags presented in vitro, and could suppress Ag-specific immune responses upon adoptive transfer into naive mice. This regulation was lost upon removal of CD4(+)CD25(+) cells. Furthermore, purified CD4(+)CD25(+) cells from the SDLN of 1,25(OH)(2)D-3-treated or UVB-irradiated mice compared with equal numbers of CD4(+)CD25(+) cells from control mice had increased capacity to suppress immune responses in both in vitro and in vivo assay systems. Following the sensitization of recipient mice with OVA, the proportion of CD4(+)Foxp3(+) cells of donor origin significantly increased in recipients of CD4(+)CD25(+) cells from the SDLN of 1,25(OH)2D3-treated mice, indicating that these regulatory T cells can expand in vivo with antigenic stimulation. These studies suggest that 1,25(OH)(2)D-3 may be an important mediator by which UVB-irradiation exerts some of its immunomodulatory effects.