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T细胞受体库动态变化及其反应突出了登革热的严重程度。

TCR repertoire dynamics and their responses underscores dengue severity.

作者信息

Khare Kriti, Yadav Sunita, Tarai Bansidhar, Budhiraja Sandeep, Pandey Rajesh

机构信息

Division of Immunology and Infectious Disease Biology, INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) laboratory, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi 110007, India.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

出版信息

iScience. 2024 Sep 16;27(10):110983. doi: 10.1016/j.isci.2024.110983. eCollection 2024 Oct 18.

Abstract

Despite recognizing the immune response's role in dengue progression, the intricate dynamics of T cell receptor (TCR) variations across DENV infection severities remain elusive. This study addresses this gap by analyzing in-house generated RNA-seq data from 112 dengue patients with varying disease severities. Our findings reveal that severe dengue patients exhibit pronounced clinical manifestations including leukopenia, thrombocytopenia, and elevated lymphocyte levels, Intriguingly, these patients also showed increased diversity in γ and δ TCR chains, unique TRGV and TRBV segment usage, and extended δ-CDR3 sequences, suggesting specialized inflammatory functions. Furthermore, mutations in the NS5 and 3'UTR regions of the dengue genome correlated with increased TRDV and TRGV chains, indicating a significant role for these mutations in the prevalence of specific TCR chains during severe infections. Overall, the study highlights the complex role of TCR repertoire in dengue pathogenesis, enhancing our understanding of TCR dynamics for future infectious diseases.

摘要

尽管认识到免疫反应在登革热病情发展中的作用,但不同登革病毒(DENV)感染严重程度下T细胞受体(TCR)变化的复杂动态仍不清楚。本研究通过分析来自112例不同疾病严重程度的登革热患者的内部生成的RNA测序数据,填补了这一空白。我们的研究结果显示,重症登革热患者表现出明显的临床表现,包括白细胞减少、血小板减少和淋巴细胞水平升高。有趣的是,这些患者还表现出γ和δ TCR链的多样性增加、独特的TRGV和TRBV区段使用以及延长的δ-CDR3序列,表明其具有特殊的炎症功能。此外,登革热基因组NS5和3'UTR区域的突变与TRDV和TRGV链增加相关,表明这些突变在严重感染期间特定TCR链的流行中起重要作用。总体而言,该研究突出了TCR库在登革热发病机制中的复杂作用,增进了我们对未来传染病中TCR动态的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0d9/11472631/34b0357481bb/fx1.jpg

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