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Distinct commensal bacteria in human nasopharyngeal lymphoid tissue associated with localized immunological memory 人鼻咽淋巴组织中与局部免疫记忆相关的独特共生菌
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-30 DOI: 10.1016/j.isci.2025.114579
Seung-Taek Park , Jina Won , Siyeon Jin , Sujin Kim , Haeun Shin , Su Hyun Lim , Ye-Ji Bang , Hyun Jik Kim
The nasopharynx (NP) serves as a primary site for localized immune responses that restrict the spread of SARS-CoV-2 to the lower respiratory tract. The microbiome is increasingly recognized as a key modulator of antiviral immunity but whether it shapes immune responses in upper airway remains uncharacterized. Detailed microbial profiles revealed that S. aureus complex abundance was the primary discriminating factor of microbial community in the NP and the enhanced abundance of S. aureus complex correlated with higher frequencies of CD4+, CD8+ tissue-resident memory T (TRM), and BRM cells. The abundance of S. aureus complex was closely associated with distinct metabolic pathways, particularly those involved in nitrogen metabolism (e.g., arginine, ornithine, and proline interconversion) and the mevalonate pathway for carotenoid biosynthesis. These findings suggest that S. aureus complex may foster unique metabolic dynamics in the NP in enhancing the tissue-residency of memory cells and localized immune responses in upper airway.
鼻咽部是限制SARS-CoV-2向下呼吸道传播的局部免疫反应的主要部位。微生物组越来越被认为是抗病毒免疫的关键调节剂,但它是否影响上呼吸道的免疫反应仍不清楚。详细的微生物图谱显示,金黄色葡萄球菌复合体丰度是NP微生物群落的主要判别因素,金黄色葡萄球菌复合体丰度的增强与CD4+、CD8+组织驻留记忆T (TRM)和BRM细胞的高频率相关。金黄色葡萄球菌复合体的丰度与不同的代谢途径密切相关,特别是涉及氮代谢的途径(如精氨酸、鸟氨酸和脯氨酸的相互转化)和类胡萝卜素生物合成的甲羟戊酸途径。这些发现表明,金黄色葡萄球菌复合物可能在NP中促进独特的代谢动力学,从而增强记忆细胞的组织驻留和上呼吸道局部免疫反应。
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引用次数: 0
Structure and function of persulfide dioxygenase from Pseudomonas aeruginosa: Implications on H2S homeostasis and interplay with nitric oxide 铜绿假单胞菌过硫双加氧酶的结构和功能:对H2S稳态和与一氧化氮相互作用的影响
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-30 DOI: 10.1016/j.isci.2025.114586
Francesca Giordano , Francesca Troilo , Martina Roberta Nastasi , Lorenzo Caruso , Marta Mellini , Carlo Travaglini-Allocatelli , Giorgio Giardina , João B. Vicente , Giordano Rampioni , Adele Di Matteo , Elena Forte , Alessandro Giuffrè
Hydrogen sulfide is an important signaling molecule, beneficial at physiological concentrations but harmful at higher levels, due to which a tight control of its bioavailability is essential. Here, we investigated persulfide dioxygenase, an enzyme involved in H2S catabolism, from the pathogen Pseudomonas aeruginosa (PaPDO). Deletion of the gene pdo led to a 4-fold increase in H2S concentration, confirming its physiological role. The recombinant enzyme was structurally characterized at 2.06 Å resolution and assigned to the metallo-β-lactamase superfamily. Compared with its human homolog, PaPDO displayed a different dimerization area and a larger active site, suggesting different substrate preferences. Functionally, PaPDO catalyzed glutathione persulfide dioxygenation with a high turnover rate, and its activity was enhanced by reduced glutathione. Interestingly, the results show that PaPDO binds to nitric oxide, which reversibly inhibits its catalytic activity. These findings reveal a novel mechanism of crosstalk between hydrogen sulfide and nitric oxide signaling and provide insights into redox regulation in a multidrug-resistant pathogen.
硫化氢是一种重要的信号分子,在生理浓度下是有益的,但在较高的浓度下是有害的,因此严格控制其生物利用度是必不可少的。在这里,我们研究了铜绿假单胞菌(PaPDO)中参与H2S分解代谢的酶过硫双加氧酶。pdo基因的缺失导致H2S浓度增加4倍,证实了其生理作用。重组酶在2.06 Å分辨率下进行了结构表征,属于金属β-内酰胺酶超家族。与人类同源物相比,PaPDO显示出不同的二聚化面积和更大的活性位点,表明不同的底物偏好。在功能上,PaPDO催化谷胱甘肽过硫双氧化具有较高的周转率,其活性被还原性谷胱甘肽增强。有趣的是,结果表明PaPDO与一氧化氮结合,可逆地抑制其催化活性。这些发现揭示了硫化氢和一氧化氮信号之间串扰的新机制,并为多重耐药病原体的氧化还原调控提供了见解。
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引用次数: 0
Exploring neglected places enabling conservation crime through place network investigations. 通过场所网络调查,探索被忽视的保护犯罪场所。
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-30 eCollection Date: 2026-01-16 DOI: 10.1016/j.isci.2025.114384
Elle Jingjing Xu, Dat Tien Trong Cao, Xin Xu, Judith J Rakowski, Luan Van Nguyen, Laure Joanny, James L Slade, Tamara D Herold, Trung Tien Cao, Meredith L Gore

Integrating local community knowledge can enhance understanding of conservation crimes when existing knowledge relies primarily on expert elicitation. We adapted place network investigations (PNI) to structure community and expert knowledge gathering about wildlife poaching around Pù Mát National Park, Vietnam. Using participatory mapping, we identified the distribution of PNI's four crime-associated place types: corruption spots, comfort spaces, convergence settings, and crime sites. We compared knowledge between conservation experts and local villagers, then explored spatial patterns of these locations. Analyses revealed previously neglected places extending beyond park boundaries. Communities contributed more extensive knowledge than experts, particularly regarding convergence settings and corruption spots. Three crime-associated place types showed positive spatial autocorrelation, with identified clusters indicating intervention priorities. This participatory approach facilitated stakeholder knowledge exchange and broadened understanding of poaching-associated spaces. Findings suggest theoretical advancements concerning spatial commonalities and distinctions between conservation and violent crime, offering a replicable model for conservation crime prevention.

当现有的知识主要依赖于专家的启发时,整合当地社区的知识可以增强对保护犯罪的理解。我们采用地点网络调查(PNI)来构建越南Pù Mát国家公园附近野生动物偷猎的社区和专家知识收集。利用参与式地图,我们确定了PNI的四种与犯罪相关的地点类型的分布:腐败点、舒适空间、收敛环境和犯罪地点。我们比较了保护专家和当地村民的知识,然后探索了这些地点的空间格局。分析显示,以前被忽视的地方延伸到了公园边界之外。社区比专家提供了更广泛的知识,特别是在趋同环境和腐败点方面。三种与犯罪相关的场所类型表现出正的空间自相关,识别出的集群表明干预的优先级。这种参与式方法促进了利益相关者的知识交流,扩大了对偷猎相关空间的理解。研究结果表明,保护与暴力犯罪之间的空间共性和区别的理论进展,为保护犯罪的预防提供了可复制的模型。
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引用次数: 0
Bta-miR-30f promotes adipogenesis and unsaturated fatty acid accumulation by targeting RAD23B in buffalo intramuscular preadipocytes Bta-miR-30f通过靶向水牛肌内前脂肪细胞RAD23B促进脂肪形成和不饱和脂肪酸积累
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-30 DOI: 10.1016/j.isci.2025.114578
Ruirui Zhu , Hao Tian , Fangfang Zou , Hongfang Mo , Yulian Xi , Xingrong Lu , Chunyan Yang , Deshun Shi , Jianghua Shang , Jieping Huang
The intramuscular fat content and the unsaturated fatty acid (UFA) composition are both critical indicators of buffalo meat quality. While microRNAs regulate fatty acid metabolism, their specific roles in buffaloes remain unclear. Our previous WGCNA identified bta-miR-30f as a hub miRNA positively correlated with UFA levels. In the present study, bta-miR-30f was found to be highly expressed in sternum subcutaneous adipose tissue and mature adipocytes. Functional studies indicated that bta-miR-30f increased lipid accumulation via enhanced adipogenesis and UFA levels, upregulating key genes including PPARG, C/EBPα, SCD, and FADS1/2. It also promoted cell proliferation. Mechanistically, the dual luciferase assay confirmed that bta-miR-30f interacted with RAD23B, whose knockdown similarly increased lipid deposition and UFA content in buffalo intramuscular preadipocytes. Thus, this study demonstrated that bta-miR-30f enhances adipogenesis differentiation and UFA accumulation by targeting RAD23B in buffalo intramuscular preadipocytes, which provides significant information for the genetic improvement of meat quality in buffaloes.
肌内脂肪含量和不饱和脂肪酸(UFA)组成是水牛肉品质的重要指标。虽然microrna调节脂肪酸代谢,但它们在水牛体内的具体作用尚不清楚。我们之前的WGCNA发现bta-miR-30f是与UFA水平正相关的枢纽miRNA。本研究发现bta-miR-30f在胸骨皮下脂肪组织和成熟脂肪细胞中高表达。功能研究表明,bta-miR-30f通过增强脂肪生成和UFA水平增加脂质积累,上调关键基因包括ppar、C/EBPα、SCD和FADS1/2。它还能促进细胞增殖。在机制上,双荧光素酶测定证实了bta-miR-30f与RAD23B相互作用,RAD23B的敲低同样增加了水牛肌内前脂肪细胞中的脂质沉积和UFA含量。因此,本研究证明bta-miR-30f通过靶向水牛肌内前脂肪细胞RAD23B促进脂肪形成分化和UFA积累,为水牛肉质遗传改良提供了重要信息。
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引用次数: 0
Arhgef7 is essential for granule cell precursor proliferation and migration during cerebellum development Arhgef7在小脑发育过程中对颗粒细胞前体增殖和迁移至关重要
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-30 DOI: 10.1016/j.isci.2025.114580
Vanesa Jiménez-Amilburu , Hugo Ducuing , Nursen Balekoglu , Sneha Sukumaran , Patricia T. Yam , Frédéric Charron
During cerebellar development, granule cell precursors (GCPs) undergo a series of tightly regulated events, including proliferation, migration, and differentiation. Arhgef7, a guanine nucleotide exchange factor for Rac1 and Cdc42, plays a crucial role in these processes. This study investigates the role of Arhgef7 in cerebellar development using conditional knockout (cKO) mice. We demonstrate that Arhgef7 is expressed in GCPs. Loss of Arhgef7 in GCPs results in severe cerebellar hypoplasia and foliation defects, particularly affecting lobules VI/VII. Arhgef7 cKO mice exhibit reduced postnatal GCP proliferation, disorganized cell layers, delayed differentiation, and impaired tangential and radial migration of GCPs. Our findings highlight the essential role of Arhgef7 in regulating multiple aspects of GCP development, thereby ensuring proper cerebellar morphogenesis.
在小脑发育过程中,颗粒细胞前体(GCPs)经历一系列严格调控的事件,包括增殖、迁移和分化。Arhgef7是Rac1和Cdc42的鸟嘌呤核苷酸交换因子,在这些过程中起着至关重要的作用。本研究利用条件敲除(cKO)小鼠研究了Arhgef7在小脑发育中的作用。我们证明Arhgef7在gcp中表达。GCPs中Arhgef7的缺失会导致严重的小脑发育不全和叶状缺损,特别是影响小叶VI/VII。Arhgef7 cKO小鼠表现出出生后GCP增殖减少,细胞层紊乱,分化延迟,GCP切向和径向迁移受损。我们的研究结果强调了Arhgef7在调节GCP发育的多个方面的重要作用,从而确保适当的小脑形态发生。
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引用次数: 0
Polarization-diversity backscatter communication based on programmable information metasurface 基于可编程信息元表面的极化分集反向散射通信
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-30 DOI: 10.1016/j.isci.2025.114577
Guoliang Luo , Xiangjin Ma , Jiaqi Han , Lihao Zhu , Rui Li , Haixia Liu , Long Li
Backscatter communication (BC) is a low-power technology that transmits data by reflecting ambient RF signals. Conventional BC, based on antenna impedance modulation, suffers from low data rates and poor interference resistance. Programmable information metasurface (IMS) offers a breakthrough by enabling precise wave control. This article presents a PIN-diode-based IMS for polarization-diversity backscatter transmission. It performs full-space secondary modulation, converting horizontally polarized incident waves into ±45° polarized signals. Operating at 5 GHz, the system uses two polarization channels with BPSK and BASK modulation to transmit the same data, achieving 2 Mbps with improved reliability through diversity. The proposed system exhibits low power consumption, strong interference resistance, and high stability, making it suitable for IoT applications such as smart healthcare and environmental monitoring.
后向散射通信(BC)是一种通过反射环境射频信号来传输数据的低功耗技术。传统的基于天线阻抗调制的无线通信存在数据速率低、抗干扰性差的问题。可编程信息元表面(IMS)通过实现精确的波控制提供了一个突破。本文提出了一种基于pin二极管的偏振分集后向散射传输IMS。它执行全空间二次调制,将水平极化入射波转换为±45°极化信号。系统工作在5ghz,采用BPSK和BASK调制的两个极化信道传输相同的数据,通过分集提高可靠性,达到2mbps。该系统功耗低,抗干扰能力强,稳定性高,适用于智能医疗、环境监测等物联网应用。
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引用次数: 0
HP1β recruits RING1A to ubiquitinate histone H2A for BRCA1-mediated resection of double-stand breaks HP1β招募RING1A使组蛋白H2A泛素化,用于brca1介导的双支架断裂切除
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-30 DOI: 10.1016/j.isci.2025.114582
Vijaya Charaka , Raj K. Pandita , Chi-Lin Tsai , Xiaoyan Wang , Sharmista Chakraborty , Kenneth S. Ramos , Sandhik Nandi , Fransisca Leonard , Vipin Singh , Partha S. Sarkar , Clayton R. Hunt , John A. Tainer , Chandrima Das , Tej K. Pandita
Efficient DNA double-strand break (DSB) repair by homologous recombination (HR), as initiated by BRCA1 recruitment orchestrated by histone and non-histone proteins, is critical to genome stability, replication, transcription, and cancer avoidance. Here we reveal Heterochromatin Protein1 beta (HP1β) promotes BRCA1 enrichment at DNA DSB sites in gene-rich regions, and this is impaired by HP1β depletion. We find that HP1β is specifically enriched at DSBs within gene-rich regions via its Chromo Shadow Domain (CSD) that interacts with both Chromatin Assembly Factor 1 and the RING1A ubiquitinase component of Polycomb Repressor Complex 1. The resulting protein complex facilitates BRCA1 recruitment by promoting H2A lysine 119 ubiquitination. Collective findings reveal a novel mechanism whereby HP1β interactions, mediated through its CSD of HP1β interaction with RING1A, promotes H2AK119 ubiquitination to facilitate BRCA1 recruitment and orchestrate efficient HR and CtIP-dependent DNA resection at DSB sites in gene-rich active chromatin.
由组蛋白和非组蛋白介导的BRCA1募集启动的同源重组(HR)有效修复DNA双链断裂(DSB),对基因组稳定、复制、转录和避免癌症至关重要。在这里,我们发现异染色质蛋白1β (HP1β)促进BRCA1在基因丰富区域的DNA DSB位点的富集,而这种富集被HP1β的缺失所破坏。我们发现HP1β通过其与染色质组装因子1和多梳抑制复合物1的RING1A泛素酶组分相互作用的色影结构域(CSD)在基因丰富区域的dsb特异性富集。由此产生的蛋白复合物通过促进H2A赖氨酸119泛素化促进BRCA1的募集。这些发现揭示了一种新的机制,通过HP1β与RING1A相互作用的CSD介导HP1β相互作用,促进H2AK119泛素化,促进BRCA1的招募,并在富含基因的活性染色质的DSB位点协调有效的HR和ctip依赖性DNA切除。
{"title":"HP1β recruits RING1A to ubiquitinate histone H2A for BRCA1-mediated resection of double-stand breaks","authors":"Vijaya Charaka ,&nbsp;Raj K. Pandita ,&nbsp;Chi-Lin Tsai ,&nbsp;Xiaoyan Wang ,&nbsp;Sharmista Chakraborty ,&nbsp;Kenneth S. Ramos ,&nbsp;Sandhik Nandi ,&nbsp;Fransisca Leonard ,&nbsp;Vipin Singh ,&nbsp;Partha S. Sarkar ,&nbsp;Clayton R. Hunt ,&nbsp;John A. Tainer ,&nbsp;Chandrima Das ,&nbsp;Tej K. Pandita","doi":"10.1016/j.isci.2025.114582","DOIUrl":"10.1016/j.isci.2025.114582","url":null,"abstract":"<div><div>Efficient DNA double-strand break (DSB) repair by homologous recombination (HR), as initiated by BRCA1 recruitment orchestrated by histone and non-histone proteins, is critical to genome stability, replication, transcription, and cancer avoidance. Here we reveal Heterochromatin Protein1 beta (HP1β) promotes BRCA1 enrichment at DNA DSB sites in gene-rich regions, and this is impaired by HP1β depletion. We find that HP1β is specifically enriched at DSBs within gene-rich regions via its Chromo Shadow Domain (CSD) that interacts with both Chromatin Assembly Factor 1 and the RING1A ubiquitinase component of Polycomb Repressor Complex 1. The resulting protein complex facilitates BRCA1 recruitment by promoting H2A lysine 119 ubiquitination. Collective findings reveal a novel mechanism whereby HP1β interactions, mediated through its CSD of HP1β interaction with RING1A, promotes H2AK119 ubiquitination to facilitate BRCA1 recruitment and orchestrate efficient HR and CtIP-dependent DNA resection at DSB sites in gene-rich active chromatin.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114582"},"PeriodicalIF":4.1,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Democratizing environmental impact assessment: An AI-augmented framework for sustainable building design 环境影响评估民主化:可持续建筑设计的人工智能增强框架
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-30 DOI: 10.1016/j.isci.2025.114589
Ali Nouri , Ming Hu
The construction sector contributes significantly to greenhouse gas emissions, yet designers often lack tools that make life cycle assessment (LCA) accessible during routine decision-making. This study presents an AI-augmented framework that embeds automated, interpretable LCA within the building information modeling environment. The system links material quantities extracted from Revit with programmatic inventory modeling and an endpoint module that allows users to adjust time horizons to reflect different cultural risk perspectives. A conversational interface enables designers and stakeholders to explore trade-offs, visualize environmental impacts, and receive plain-language interpretations of results. Using a residential building model, the framework reproduced expert SimaPro outputs with less than 2.1% variation across indicators. By integrating environmental intelligence directly into early-stage design workflows, the approach supports more informed material choices, streamlines green permitting, and provides a foundation for policy tools that encourage lower-carbon construction.
建筑行业对温室气体排放的贡献很大,但设计师往往缺乏在日常决策中进行生命周期评估(LCA)的工具。本研究提出了一个人工智能增强框架,该框架将自动化、可解释的LCA嵌入到建筑信息建模环境中。该系统将从Revit中提取的材料数量与可编程库存建模和端点模块联系起来,该模块允许用户调整时间范围以反映不同的文化风险视角。对话界面使设计人员和利益相关者能够探索权衡,可视化环境影响,并接收结果的简单语言解释。使用住宅建筑模型,该框架再现了专家SimaPro的输出,各指标之间的差异小于2.1%。通过将环境智能直接整合到早期设计工作流程中,该方法支持更明智的材料选择,简化了绿色许可,并为鼓励低碳建筑的政策工具提供了基础。
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引用次数: 0
Interpretable machine learning for predicting low-dose methylprednisolone effectiveness in long COVID 预测低剂量甲基强的松龙在长期COVID中的有效性的可解释机器学习
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-30 DOI: 10.1016/j.isci.2025.114574
Jisheng Zhang , Yang Chen , Aijun Zhang , Yi Yang , Liqian Ma , Kewei Yu , Weitao Zhang , Xiaojing Ye , Jiangsong Zhang , Ke Lin , Xianming Lin
Long COVID is a chronic, multisystem disease with limited response to conventional treatments. While low-dose methylprednisolone has shown effectiveness in some patients, individual responses vary, and accurate predictive tools are lacking. This retrospective study included 330 long COVID patients who received low-dose methylprednisolone treatment across three hospitals. Patients were divided into training (n = 202), test (n = 33), and external validation sets (n = 53, n = 42). Using least absolute shrinkage and selection operator (LASSO) regression, 38 variables were analyzed to develop six machine learning models. The logistic regression (LR) model showed stable performance across all datasets (AUCs: 0.8715, 0.7198, 0.8419, and 0.8676), making it the final model selected. SHapley Additive exPlanations (SHAP) analysis identified seven key variables, which were used to construct a nomogram for predicting treatment efficacy. The LR model and nomogram demonstrated strong predictive performance and clinical interpretability, offering a valuable decision-support tool for individualized treatment of long COVID with low-dose methylprednisolone.
新冠肺炎是一种慢性多系统疾病,对常规治疗的反应有限。虽然低剂量甲基强的松龙在一些患者中显示出有效性,但个体反应不同,并且缺乏准确的预测工具。这项回顾性研究包括来自三家医院的330名接受低剂量甲基强的松龙治疗的长COVID患者。患者被分为训练组(n = 202)、测试组(n = 33)和外部验证组(n = 53, n = 42)。使用最小绝对收缩和选择算子(LASSO)回归,分析了38个变量,开发了6个机器学习模型。逻辑回归(LR)模型在所有数据集上表现稳定(auc: 0.8715, 0.7198, 0.8419和0.8676),使其成为最终选择的模型。SHapley加性解释(SHAP)分析确定了七个关键变量,用于构建预测治疗疗效的nomogram。LR模型和nomogram表现出较强的预测能力和临床可解释性,为低剂量甲基强的松龙个体化治疗长期COVID提供了有价值的决策支持工具。
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引用次数: 0
Activation phenotypes defined by the coordinated expression of activation markers discriminate TCR-mediated and bystander T cell responses 激活表型由激活标记的协调表达定义,区分tcr介导的和旁观者T细胞反应
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-29 DOI: 10.1016/j.isci.2025.114551
Tamara J.C. Schenk , Martijn Vos , Yannick van Sleen , Debbie van Baarle , Teun Guichelaar
Studying activation of antigen-specific T cells is essential for understanding adaptive immune response to pathogens, tumors, and vaccines. Flow cytometry is commonly used to identify antigen-specific T cells based on the induction of activation-induced markers (AIMs). However, these markers are also expressed on bystander T cells activated by cytokines produced by antigen-activated T cells. This complicates the distinction between true T cell receptor (TCR)-activated- and bystander T cells. We developed an approach to differentiate between these types of cells. We stimulated human PBMCs with anti-CD3 antibody (TCR-mediated) or supernatant of activated T cells, IL-2, or IL-15 (bystander activation). We analyzed AIM co-expression patterns on CD4+ and CD8+ T cells, and defined activation phenotypes that distinguish TCR-activated from bystander-activated T cells. In anti-viral responses, peptide stimulation mainly induced bystander activation, yet bystander T cells contributed minimally to cytokine production. Our findings provide a framework for identifying T cell response types in diverse clinical contexts.
研究抗原特异性T细胞的活化对于理解对病原体、肿瘤和疫苗的适应性免疫反应至关重要。流式细胞术通常用于基于激活诱导标记(AIMs)的诱导来鉴定抗原特异性T细胞。然而,这些标记也在被抗原激活的T细胞产生的细胞因子激活的旁观者T细胞上表达。这使得真正的T细胞受体(TCR)激活T细胞和旁观者T细胞之间的区别变得复杂。我们开发了一种方法来区分这些类型的细胞。我们用抗cd3抗体(tcr介导)或活化T细胞、IL-2或IL-15(旁观者活化)的上清液刺激人PBMCs。我们分析了AIM在CD4+和CD8+ T细胞上的共表达模式,并定义了区分tcr激活和旁观者激活T细胞的激活表型。在抗病毒反应中,肽刺激主要诱导旁观者T细胞激活,但旁观者T细胞对细胞因子的产生贡献最小。我们的研究结果为在不同的临床环境中识别T细胞反应类型提供了一个框架。
{"title":"Activation phenotypes defined by the coordinated expression of activation markers discriminate TCR-mediated and bystander T cell responses","authors":"Tamara J.C. Schenk ,&nbsp;Martijn Vos ,&nbsp;Yannick van Sleen ,&nbsp;Debbie van Baarle ,&nbsp;Teun Guichelaar","doi":"10.1016/j.isci.2025.114551","DOIUrl":"10.1016/j.isci.2025.114551","url":null,"abstract":"<div><div>Studying activation of antigen-specific T cells is essential for understanding adaptive immune response to pathogens, tumors, and vaccines. Flow cytometry is commonly used to identify antigen-specific T cells based on the induction of activation-induced markers (AIMs). However, these markers are also expressed on bystander T cells activated by cytokines produced by antigen-activated T cells. This complicates the distinction between true T cell receptor (TCR)-activated- and bystander T cells. We developed an approach to differentiate between these types of cells. We stimulated human PBMCs with anti-CD3 antibody (TCR-mediated) or supernatant of activated T cells, IL-2, or IL-15 (bystander activation). We analyzed AIM co-expression patterns on CD4<sup>+</sup> and CD8<sup>+</sup> T cells, and defined activation phenotypes that distinguish TCR-activated from bystander-activated T cells. In anti-viral responses, peptide stimulation mainly induced bystander activation, yet bystander T cells contributed minimally to cytokine production. Our findings provide a framework for identifying T cell response types in diverse clinical contexts.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114551"},"PeriodicalIF":4.1,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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