IFN-β induces the proliferation of CD4+CD25+Foxp3+ regulatory T cells through upregulation of GITRL on dendritic cells in the treatment of multiple sclerosis
IFN-β induces the proliferation of CD4+CD25+Foxp3+ regulatory T cells through upregulation of GITRL on dendritic cells in the treatment of multiple sclerosis
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DOI：
10.1016/j.jneuroim.2011.10.014
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发表时间：
2012-01-18
影响因子：
3.3
通讯作者：
Hong, Jian
中科院分区：
文献类型：
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作者：
Chen, Meiyue;Chen, Guangjie;Hong, Jian
IFN-β是用于治疗多发性硬化（MS）的主要疾病调节剂。其机制复杂，对多种类型的免疫细胞具有广泛的免疫调节作用。临床上观察到，在用IFN-β治疗的一些MS患者中，CD 4（+）CD 25（+）Foxp 3（+）调节性T细胞的数量增加。在这项研究中，我们发现IFN-β与IFNAR的结合通过调节树突状细胞（DC）扩增了天然存在的CD 4（+）CD 25（+）Foxp 3（+）调节性T细胞群。IFN-β对CD 4（+）CD 25（-）T细胞向适应性Treg细胞的转化没有影响。IFN-β诱导的DC上GITRL的上调和Treg细胞上CTLA-4的下调共同作用以促进无能Treg细胞的增殖。在用Avonex或Rebif（IFN-β）治疗的MS患者中，发现GITRL表达在外周CD 14（+）细胞上显著上调。我们的研究结果有助于更好地了解IFN-β在MS治疗中的复杂作用。（C）2011 Elsevier B. V.保留所有权利。
IFN-beta is a major disease-modifying agent used for the treatment of multiple sclerosis (MS). Its mechanisms are complex and it has broad immunomodulatory effects on many types of immune cells. It was observed clinically that the quantity of CD4(+)CD25(+)Foxp3(+) regulatory T cells increases in some MS patients treated with IFN-beta. In this study, we show that IFNAR engagement by IFN-beta expands naturally occurring CD4(+)CD25(+)Foxp3(+) regulatory T cell population through the modulation of dendritic cells (DCs). IFN-beta has no effect on the conversion of CD4(+)CD25(-) T cells to adaptive Treg cells. The IFN-beta-induced upregulation of GITRL on DC and downregulation of CTLA-4 on Treg cell work together to facilitate the proliferation of anergic Treg cells. In MS patients treated with Avonex or Rebif (IFN-beta), it was found that GITRL expression is markedly upregulated on peripheral CD14(+) cells. Our findings help the better understanding of the complex effects of IFN-beta in the treatment of MS. (C) 2011 Elsevier B.V. All rights reserved.