Anti-IFN-α/β receptor antibody treatment ameliorates disease in lupus-predisposed mice.
Anti-IFN-α/β receptor antibody treatment ameliorates disease in lupus-predisposed mice.
复制标题
DOI：
10.4049/jimmunol.1201477
复制
发表时间：
2012-12-15
期刊：
影响因子：
--
通讯作者：
Theofilopoulos AN
中科院分区：
文献类型：
--
作者：
Baccala R;Gonzalez-Quintial R;Schreiber RD;Lawson BR;Kono DH;Theofilopoulos AN
在人类和小鼠中证明核酸敏感Toll样受体（TLR）和I型干扰素（IFN）是必需的疾病介质是描绘狼疮发病机制的里程碑。在这里，我们表明，Ifnb基因缺失不会改变NZB小鼠的疾病进展，从而强烈暗示IFN-α亚型作为主要的致病效应。我们进一步证明了用小鼠源性抗IFNAR抗体长期治疗雄性BXSB小鼠减少了血清学、细胞学和组织学疾病表现并延长了生存期，表明在该模型中由Tlr 7基因复制引起的疾病加速是由I型IFN信号传导介导的。当在疾病过程的早期应用时，这种治疗在BXSB小鼠中的疗效是明显的，但是当在后期阶段开始治疗时，仅观察到一些疾病特征的部分减少。在MRL-Faslpr模型中也观察到一过性治疗效应，但总体死亡率未受影响。综合研究结果表明，IFNAR阻断，特别是在疾病早期阶段开始时，可能是人类SLE和其他自身免疫综合征的一种有用的治疗方法。
The demonstration in humans and mice that nucleic acid-sensing Toll-like receptors (TLRs) and type I interferons (IFNs) are essential disease mediators is a milestone in delineating the mechanisms of lupus pathogenesis. Here, we show that Ifnb gene deletion does not modify disease progression in NZB mice, thereby strongly implicating IFN-α subtypes as the principal pathogenic effectors. We further document that long-term treatment of male BXSB mice with an anti-IFNAR antibody of mouse origin reduced serologic, cellular and histologic disease manifestations and extended survival, suggesting that disease acceleration by the Tlr7 gene duplication in this model is mediated by type I IFN signaling. The efficacy of this treatment in BXSB mice was clearly evident when applied early in the disease process, but only partial reductions in some disease characteristics were observed when treatment was initiated at later stages. A transient therapeutic effect was also noted in the MRL-Faslpr model, although overall mortality was unaffected. The combined findings suggest that IFNAR blockade, particularly when started at early disease stages, may be a useful treatment approach for human SLE and other autoimmune syndromes.
登录
查看更多内容
影响因子：
4.4
作者：
Kerkmann, M;Rothenfusser, S;Hartmann, G
通讯作者：
Hartmann, G
影响因子：
20.3
作者：
Hao, Yi;O'Neill, Patrick;Cancro, Michael P.
通讯作者：
Cancro, Michael P.
全身IFN-α在B6.SLE123小鼠中驱动肾脏肾炎。
影响因子：
5.4
作者：
Fairhurst, Anna-Marie;Mathian, Alexis;Connolly, John E.;Wang, Andrew;Gray, Hillery F.;George, Tiffany A.;Boudreaux, Christopher D.;Zhou, Xin J.;Li, Quan-Zhen;Koutouzov, Sophie;Banchereau, Jacques;Wakeland, Edward K.
通讯作者：
Wakeland, Edward K.
DOI：
10.4049/jimmunol.1000466
发表时间：
2011-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jacob N;Guo S;Mathian A;Koss MN;Gindea S;Putterman C;Jacob CO;Stohl W
通讯作者：
Stohl W
影响因子：
--
作者：
Kirou, KA;Lee, C;Crow, MK
通讯作者：
Crow, MK