用于MS研究的人源化小鼠

IF 27.6 1区医学 Q1 IMMUNOLOGY

Nature Immunology Pub Date : 2025-08-29 DOI:10.1038/s41590-025-02273-w

Laurie A. Dempsey

引用次数: 0

摘要

多发性硬化症（MS）以前与eb病毒（EBV）感染有关，具有HLA-DR2b单倍型的个体遗传易感性风险更高。EBV感染如何使这些个体容易发展为神经性自身免疫尚不清楚。在Nature中，Läderach等人产生了表达HLA-DR2b的人源化小鼠作为ms模型来检测EBV诱导的神经病理学。这种小鼠很容易被EBV感染，感染后6周内可在脑组织中检测到EBV，并伴有活化和效应记忆T细胞的浸润。表达T-bet和CXCR3的EBV+ B细胞克隆扩增，脑组织中T-bet+CXCR3+ B细胞克隆型高度富集。研究发现，CXCR3的表达对于EBV+ B细胞定位到大脑的脑膜下区域是必要的，在那里它们表达吸引T细胞的趋化因子。T-bet+CXCR3+ B细胞与活化的T细胞聚集在一起，包括那些表达识别自身抗原的IgM的T细胞，这表明这些B细胞可以在EBV感染时引发潜在的致病性T细胞。在该模型中，利妥昔单抗介导的B细胞耗竭也导致大脑中CD4+ T细胞活化减少。未来使用这种新的人源化hla - dr2b转基因小鼠模型将为ms的发病机制提供新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Humanized mice for MS studies

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来源期刊

Nature Immunology 医学-免疫学

CiteScore

40.00

自引率

2.30%

发文量

248

审稿时长

4-8 weeks

期刊介绍： Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.