Notch1 signaling and regulatory T cell function

被引:73
|
作者
Asano, Naoki [1 ]
Watanabe, Tomohiro [1 ,2 ]
Kitani, Atsushi [1 ]
Fuss, Ivan J. [1 ]
Strober, Warren [1 ]
机构
[1] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA
[2] Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Kyoto, Japan
来源
JOURNAL OF IMMUNOLOGY | 2008年 / 180卷 / 05期
关键词
D O I
10.4049/jimmunol.180.5.2796
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Previous studies have shown that the Notch1 and TGF-beta signaling pathways are mutually re-enforcing. Given recent evidence that regulatory T cell (Treg) effector function is mediated by TGF-beta signaling, we investigated whether Notch1 signaling also participated in Treg effector function. Initial studies showed that Notch1 ligands, particularly Jagged1, are present on Tregs and that, indeed, blockade of Notch1 signaling with an anti-jagged1 or a blocking anti-Notch1 Ab inhibits Treg suppressor function in vitro. We then showed that a signaling component generated by Notch1 activation (Notch1 intracellular domain) of dendritic cells physically interacts with a signaling component generated by TGF-beta signaling (pSmad3). Furthermore, this interaction has functional downstream effects because over-expression of Notch1 intracellular domain facilitates pSmad3 translocation to the nucleus and enhances pSmad3 transcriptional activity of a Smad-sensitive promoter linked to a luciferase reporter. Finally, we showed that blockade of TGF-beta signaling and Notch signaling did not have additive inhibitory effects on Treg suppressor function. These results are consistent with the conclusion that Notch1 signaling facilitates TGF-beta-mediated effector function of Tregs.
引用
收藏
页码:2796 / 2804
页数:9
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