与缺血性脑卒中患者全身免疫反应有关的 T 细胞受体谱系特征。

IF 4.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yan Zong, Yuanyuan Liu, Junyang Wang, Yousef Rastegar-Kashkooli, Peiji Fu, Shuai Chen, Qianlin Zhang, Maosen Huang, Junmin Wang, Jiewen Zhang, Jian Wang, Chao Jiang
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引用次数: 0

摘要

T 淋巴细胞在中风后的免疫炎症反应中起着至关重要的作用。然而,脑卒中后大脑和外周组织中的 T 细胞功能截然不同,其背后的具体机制仍不清楚,需要进一步研究。T细胞受体(TCR)对控制T淋巴细胞的发育和活跃至关重要。本研究旨在通过分析急性缺血性脑卒中(AIS)患者体内的 TCR 重排来深入了解 T 淋巴细胞的生物功能。我们对 25 名 AIS 患者和 10 名健康对照者的外周血样本进行了高通量 TCR 测序。我们比较了 T 细胞的百分比和 TCR 重排的特征,特别关注 V(D)J 基因片段的重组和 Vβ 基因互补决定区 3 (CDR3) 的多样性。此外,本研究还分析了 AIS 患者 TCR 反应谱偏斜的潜在生物学意义。与健康对照组相比,AIS 患者的循环淋巴细胞比例(LY%)下降,而全身免疫炎症指数(SII)上升。TCR读数对的平均数量减少,这与淋巴细胞减少症的存在相对应。然而,在 AIS 患者的外周血中,V(D)J 基因片段的重组、CDR3 克隆型的数量和 CDR3 的多样性都有所增加。此外,CDR3 氨基酸或核苷酸克隆型数量的增加与神经功能缺损呈负相关,但与 AIS 患者的全身免疫状况和功能预后呈正相关。我们的研究结果表明,AIS 患者的外周可能同时存在免疫抑制和抗原特异性 T 细胞反应增强。进一步研究这些对立变化的机制可能会发现新的靶点,以逆转免疫抑制或减轻 T 细胞对 AIS 患者病变脑部的有害影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The characteristics of T-cell receptor repertoire in relation to systemic immune response of patients with ischemic stroke.

T lymphocytes play a vital role in the immune-inflammatory response following a stroke. However, the specific mechanisms behind the contrasting functions of T cells in the brain and peripheral tissues after a stroke remain unclear and require further investigation. T-cell receptors (TCRs) are essential in controlling how T lymphocytes develop and become active. This study aims to gain a deeper understanding of the biological function of T lymphocytes by analyzing the TCR repertoire in patients who have experienced an acute ischemic stroke (AIS). High-throughput TCR sequencing was conducted on peripheral blood samples from 25 AIS patients and 10 healthy controls. We compared the percentage of T cells and the characteristics of the TCR repertoire, specifically focusing on the recombination of V(D)J gene fragments and the diversity of the complementarity determining region 3 (CDR3) of the Vβ gene. Additionally, this study analyzed the potential biological significance of the skewed TCR repertoire in AIS patients. In patients with AIS, the proportion of circulating lymphocytes (LY%) decreased while the systemic immune-inflammatory index (SII) increased compared to healthy controls. The average number of TCR read pairs decreased, corresponding with the presence of lymphopenia. However, the recombination of V(D)J gene fragments, the number of CDR3 clonotypes, and the diversity of CDR3 was elevated in the peripheral blood of AIS patients. Furthermore, the increased number of CDR3 amino acid or nucleotide clonotypes was negatively correlated with neurologic deficits but positively correlated with AIS patients' systemic immune condition and functional outcomes. Our findings suggest that both immunosuppression and enhanced antigen-specific T-cell response may exist in the periphery of the AIS patients. Further investigation into the mechanisms underlying these opposing changes may lead to the discovery of novel targets to reverse immunosuppression or mitigate the detrimental effects of T cells in the lesioned brain of AIS patients.

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来源期刊
Journal of Neurochemistry
Journal of Neurochemistry 医学-神经科学
CiteScore
9.30
自引率
2.10%
发文量
181
审稿时长
2.2 months
期刊介绍: Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.
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