自反应 T 细胞靶向狼疮中的新自身抗原

IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY Nature genetics Pub Date : 2024-10-10 DOI:10.1038/s41588-024-01955-9
Kyle Vogan
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引用次数: 0

摘要

不变链的表达减少会影响主要组织相容性复合体 II 类(MHC-II)的抗原呈递,从而引发针对异常自身抗原(称为新自身抗原)的自身抗体的产生。为了进一步研究这些过程在体内的影响,Mori 等人制造了携带不变链诱导性基因敲除等位基因的小鼠。他们发现,在成年小鼠体内消减不变链会导致狼疮样全身表型,并伴随着新自身抗原在 MHC-II 上的呈现、自身反应性 B 细胞和 T 细胞的激活以及新自身反应性 T 细胞的克隆扩增。接着,他们分析了系统性红斑狼疮(SLE)人类患者与健康对照组的 T 细胞受体(TCR)的复合物,发现识别新自身抗原的 TCR 特异性地存在于系统性红斑狼疮患者体内,约占其 TCR 复合物的 10%。值得注意的是,他们还发现有证据表明,Epstein-Barr 病毒(EBV)(一种已知的系统性红斑狼疮风险因素)的再活化会导致不变链表达的减少以及新自身抗原在 MHC-II 上呈现的相应增加。总之,这些结果提供了一个合理的模型,将 EBV 再激活与新自身抗原的异常产生联系起来,作为驱动系统性红斑狼疮的自身免疫过程的病因触发因素:细胞 https://doi.org/10.1016/j.cell.2024.08.025 (2024)
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来源期刊
Nature genetics
Nature genetics 生物-遗传学
CiteScore
43.00
自引率
2.60%
发文量
241
审稿时长
3 months
期刊介绍: Nature Genetics publishes the very highest quality research in genetics. It encompasses genetic and functional genomic studies on human and plant traits and on other model organisms. Current emphasis is on the genetic basis for common and complex diseases and on the functional mechanism, architecture and evolution of gene networks, studied by experimental perturbation. Integrative genetic topics comprise, but are not limited to: -Genes in the pathology of human disease -Molecular analysis of simple and complex genetic traits -Cancer genetics -Agricultural genomics -Developmental genetics -Regulatory variation in gene expression -Strategies and technologies for extracting function from genomic data -Pharmacological genomics -Genome evolution
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