nature-immunology201212-8

补体受体CD46和Notch- Jagged 系统是辅助T细胞分化的关键。来自英国伦敦国王学院的Kemper及其同事证实Jagged1蛋白是CD46的配体,且它对人1型T辅助细胞的分化起关键作用。相关的研究论文于10月21日在线发表在《Nature Immunology》期刊上。

-2012年12月《自然-免疫》

中文翻译


【题目】CD46与Jagged1互作是人类TH1免疫反应的关键

【译文】CD46是补体调节蛋白,它在与免疫响应的相关反应中起重要的作用。CD46在功能上可作为病原受体,它是诱导效应1型T辅助细胞(TH1)分泌干扰素-γ (IFN-γ)的潜在辅助刺激因子,随后则会诱导调节T细胞分泌白介素10(IL-10)。本研究鉴定到Notch家族成员蛋白Jagged1是CD46    的配体。此外,我们发现在T细胞活化过程中,CD46调控Notch受体及其配体的表达,还发现若干扰CD46与Jagged1信号途径的串话,会阻断IFN-γ的诱导,转而诱导IL-10。特别地是,来自CD46缺陷的病人的CD4+ T细胞中Jagged1蛋白的编码基因会发生次形态突变(艾欧吉勒综合征的发病原因),导致无论是体外还是体内情况下,CD4+ T细胞都难以产生适当的TH1响应,这表明CD46与Jagged1信号途径的串话是这些病人的CD4+ T细胞反复感染的原因。

英文原稿


[Title]: The CD46-Jagged1 interaction is critical for human TH1 immunity

[Authors]:: Gaëlle Le Friec,Devon Sheppard, Pat Whiteman, Christian M Karsten, Salley Al-Tilib Shamoun, Adam Laing, Laurence Bugeon, Margaret J Dallman, Teresa Melchionna, Chandramouli Chillakuri, Richard A Smith, Christian Drouet, Lionel Couzi, Veronique Fremeaux-Bacchi, Jörg Köhl, Simon N Waddington, James M McDonnell, Alastair Baker, Penny A Handford, Susan M Lea & Claudia Kemper

[Abstract]: CD46 is a complement regulator with important roles related to the immune response. CD46 functions as a pathogen receptor and is a potent costimulator for the induction of interferon-γ (IFN-γ)-secreting effector T helper type 1 (TH1) cells and their subsequent switch into interleukin 10 (IL-10)-producing regulatory T cells. Here we identified the Notch family member Jagged1 as a physiological ligand for CD46. Furthermore, we found that CD46 regulated the expression of Notch receptors and ligands during T cell activation and that disturbance of the CD46-Notch crosstalk impeded induction of IFN-γ and switching to IL-10. Notably, CD4+ T cells from CD46-deficient patients and patients with hypomorphic mutations in the gene encoding Jagged1 (Alagille syndrome) failed to mount appropriate TH1 responses in vitro and in vivo, which suggested that CD46-Jagged1 crosstalk is responsible for the recurrent infections in subpopulations of these patients.

原文地址

http://www.nature.com/ni/journal/v13/n12/full/ni.2454.html

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