Immunology最新文献

{"title":"Identification of different functions of CD8+ T cell subpopulations by a novel monoclonal antibody","authors":"Kantinan Chuensirikulchai,&nbsp;Supansa Pata,&nbsp;Witida Laopajon,&nbsp;Nuchjira Takheaw,&nbsp;Kamonporn Kotemul,&nbsp;Kanyaruck Jindaphun,&nbsp;Saichit Khummuang,&nbsp;Watchara Kasinrerk","doi":"10.1111/imm.13826","DOIUrl":"10.1111/imm.13826","url":null,"abstract":"<p>The explicit identification of CD8⁺ T cell subpopulation is important for deciphering the role of CD8⁺ T cells for protecting our body against invading pathogens and cancer. Our generated monoclonal antibody (mAb), named FE-1H10, recognized two novel subpopulations of peripheral blood CD8⁺ T cells, FE-1H10⁺ and FE-1H10⁻ CD8⁺ T cells. The molecule recognized by mAb FE-1H10 (FE-1H10 molecules) had a higher distribution on effector memory CD8⁺ T cell subsets. The functions of FE-1H10⁻ and FE-1H10⁺ CD8⁺ T cells were investigated. T cell proliferation assays revealed that FE-1H10⁻ CD8⁺ T cells exhibited a higher proliferation rate than FE-1H10⁺ CD8⁺ T cells, whereas FE-1H10⁺ CD8⁺ T cells produced higher levels of IFN-γ and TNF-α than FE-1H10⁻ CD8⁺ T cells. In T cell cytotoxicity assays, FE-1H10⁺ CD8⁺ T cells were able to kill target cells better than FE-1H10⁻ CD8⁺ T cells. RNA-sequencing analysis confirmed that these subpopulations were distinct: FE-1H10⁺ CD8⁺ T cells have higher expression of genes involved in effector functions (<i>IFNG</i>, <i>TNF</i>, <i>GZMB</i>, <i>PRF1</i>, <i>GNLY</i>, <i>FASL</i>, <i>CX3CR1</i>) while FE-1H10⁻ CD8⁺ T cells have greater expression of genes related to memory CD8⁺ T cell populations (<i>CCR7</i>, <i>SELL</i>, <i>TCF7</i>, <i>CD40LG</i>). The results suggested that mAb FE-1H10 identifies two novel distinctive CD8⁺ T cell subpopulations. The FE-1H10⁺ CD8⁺ T cells carried a superior functionality in response to tumour cells. The uncover of these novel CD8⁺ T cell subpopulations may be the basis knowledge of an optional immunotherapy for the selection of potential CD8⁺ T cells in cancer treatment.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"321-338"},"PeriodicalIF":4.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-10 indirectly modulates functional activity of CD4+CD28null T-lymphocytes through LFA-3 and HLA class II inhibition","authors":"Alejandra García-Torre,&nbsp;Eva Bueno-García,&nbsp;Marco A. Moro-García,&nbsp;Rocío López-Martínez,&nbsp;Beatriz Rioseras,&nbsp;Beatriz Díaz-Molina,&nbsp;José Luis Lambert,&nbsp;Rebeca Alonso-Arias","doi":"10.1111/imm.13824","DOIUrl":"10.1111/imm.13824","url":null,"abstract":"<p>Expansion of CD4⁺CD28^null T-lymphocytes is common in chronic heart failure (CHF) patients. Its ability to produce high levels of proinflammatory cytokines is probably the key role of these cells in CHF. IL-10 is a candidate for limiting CD4⁺CD28^null T-lymphocyte responses, whereas tumour necrosis factor (TNF) is the cytokine most closely involved in the loss of CD28 expression. Serum levels of TNF and IL-10 were measured in 65 CHF patients (mean age, 65.2 ± 13.84 years). Patients with an IL-10/TNF ratio ≥1 had significantly lower levels of CD4⁺CD28^null T-lymphocytes than those with a ratio &lt;1. In vitro, IL-10 reduced the frequency of proliferative CD4⁺CD28^null T-lymphocytes stimulated with anti-CD3. Pre-treatment with IL-10 before anti-CD3 stimulation was required for the cytokine to inhibit TNF production by CD4⁺CD28^null T-lymphocytes. In addition to the previously described effect of IL-10 on HLA-DR and ICAM-1 expression, LFA-3 protein and mRNA levels were reduced in the presence of the cytokine in monocytes. IL-10 inhibition on CD4⁺CD28^null T-lymphocytes may be mediated by a reduction in HLA class II and LFA-3 expression because blocking interactions with these costimulators has similar effects to those of IL-10 treatment. Moreover, costimulation through CD2/LFA-3 interaction is enough to induce proliferation and cytokine production in CD4⁺CD28^null T-lymphocytes.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"296-309"},"PeriodicalIF":4.9,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD5L is upregulated upon infection with Mycobacterium tuberculosis with no effect on disease progression","authors":"Marcos S. Cardoso,&nbsp;Rute Gonçalves,&nbsp;Liliana Oliveira,&nbsp;Diogo Silvério,&nbsp;Érica Téllez,&nbsp;Tony Paul,&nbsp;Maria Rosa Sarrias,&nbsp;Alexandre M. Carmo,&nbsp;Margarida Saraiva","doi":"10.1111/imm.13825","DOIUrl":"10.1111/imm.13825","url":null,"abstract":"<p>Tuberculosis (TB) alone caused over a billion deaths in the last 200 years, making it one of the deadliest diseases to humankind. Understanding the immune mechanisms underlying protection or pathology in TB is key to uncover the much needed innovative approaches to tackle TB. The scavenger receptor cysteine-rich molecule CD5 antigen-like (CD5L) has been associated with TB, but whether and how CD5L shapes the immune response during the course of disease remains poorly understood. Here, we show an upregulation of CD5L in circulation and at the site of infection in C57BL/6 <i>Mycobacterium tuberculosis</i>-infected mice. To investigate the role of CD5L in TB, we studied the progression of <i>M. tuberculosis</i> aerosol infection in a recently described genetically engineered mouse model lacking CD5L. Despite the increase of CD5L during infection of wild-type mice, absence of CD5L did not impact bacterial burden, histopathology or survival of infected mice. Absence of CD5L associated with a modest increase in the numbers of CD4+ T cells and the expression of IFN-γ in the lungs of infected mice, with no major effect in overall immune cell dynamics. Collectively, this study confirms CD5L as a potential diagnostic biomarker to TB, showing no discernible impact on the outcome of the infection.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"310-320"},"PeriodicalIF":4.9,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-2 amplifies quantitative TCR signalling inputs to drive Th1 and Th2 differentiation","authors":"Mohammad Ameen Al-Aghbar,&nbsp;Meritxell Espino Guarch,&nbsp;Nicholas van Panhuys","doi":"10.1111/imm.13821","DOIUrl":"10.1111/imm.13821","url":null,"abstract":"<p>The activation of CD4+ T-cells in a T cell receptor (TCR)-dependent antigen-specific manner is a central characteristic of the adaptive immune response. In addition to ensuring that CD4+ T-cells recognise their cognate antigen during activation, TCR-mediated signalling can also direct the outcome of differentiation. In both in vivo and in vitro model systems, strong TCR signalling has been demonstrated to drive Th1 differentiation, whereas weak TCR signalling drives Th2 responses. During the process of differentiation, TCR signal strength acts as a quantitative component in combination with the qualitative effects imparted by cytokines to polarise distinct T-helper lineages. Here, we investigated the role of interleukin 2 (IL-2) signalling in determining the outcome of TCR-dependent differentiation. IL-2 production was initiated as an early response to TCR-induced activation and was regulated by the strength of TCR signalling initially received. In the absence of IL-2, TCR dependent differentiation was found to be abolished. However, proliferative responses and early markers of activation were maintained, including the upregulation of GATA3, Tbet and Foxp3 at 24 h post-stimulation. Demonstrating that IL-2 signalling has a key role in stabilising and amplifying lineage-specific transcirption factor expression during differentiation. Further, activation of IL-2-deficient T-cells in the presence of exogenous cytokines was sufficient to restore differentiation whilst maintaining transcriptional signatures imparted during initial TCR signalling. Combined, our data demonstrate that the integration of quantitative TCR-dependent signalling and qualitative IL-2 signalling is essential for determining the fate of CD4+ T-cells during differentiation.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"196-208"},"PeriodicalIF":4.9,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of novel protein acylation modifications in immunity and its related diseases","authors":"Xiaoqian Li,&nbsp;Tao Yu,&nbsp;Xiaolu Li,&nbsp;Xiangqin He,&nbsp;Bei Zhang,&nbsp;Yanyan Yang","doi":"10.1111/imm.13822","DOIUrl":"10.1111/imm.13822","url":null,"abstract":"<p>The cross-regulation of immunity and metabolism is currently a research hotspot in life sciences and immunology. Metabolic immunology plays an important role in cutting-edge fields such as metabolic regulatory mechanisms in immune cell development and function, and metabolic targets and immune-related disease pathways. Protein post-translational modification (PTM) is a key epigenetic mechanism that regulates various biological processes and highlights metabolite functions. Currently, more than 400 PTM types have been identified to affect the functions of several proteins. Among these, metabolic PTMs, particularly various newly identified histone or non-histone acylation modifications, can effectively regulate various functions, processes and diseases of the immune system, as well as immune-related diseases. Thus, drugs aimed at targeted acylation modification can have substantial therapeutic potential in regulating immunity, indicating a new direction for further clinical translational research. This review summarises the characteristics and functions of seven novel lysine acylation modifications, including succinylation, S-palmitoylation, lactylation, crotonylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation and malonylation, and their association with immunity, thereby providing valuable references for the diagnosis and treatment of immune disorders associated with new acylation modifications.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"53-75"},"PeriodicalIF":4.9,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13822","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of SETD2 maintains immune regulatory function in macrophages to suppress airway allergy","authors":"Lei Zhang,&nbsp;Junyi Wang,&nbsp;Xiaoyu Liu,&nbsp;Xiaojun Xiao,&nbsp;Yu Liu,&nbsp;Qinmiao Huang,&nbsp;Jing Li,&nbsp;Guoping Li,&nbsp;Pingchang Yang","doi":"10.1111/imm.13823","DOIUrl":"10.1111/imm.13823","url":null,"abstract":"<p>SET domain-containing 2 (SETD2) is a histone methyltransferase. It regulates the activity of H3K36me3 to enhance gene transcription. Macrophages (Mϕs) are one of the cell types involved in immune response. The purpose of this study is to clarify the role of SETD2 in regulating the immune property of Mϕ. The Mφs were isolated from the bronchoalveolar lavage fluid (BALF) and analysed through flow cytometry and RNA sequencing. A mouse strain carrying Mφs deficient in SETD2 was used. A mouse model of airway allergy was established with the ovalbumin/alum protocol. Less expression of SETD2 was observed in airway Mϕs in patients with allergic asthma. SETD2 of M2 cells was associated with the asthmatic clinical response. Sensitization reduced the expression of SETD2 in mouse respiratory tract M2 cells, which is associated with the allergic reaction. Depletion of SETD2 in Mφs resulted in Th2 pattern inflammation in the lungs. SETD2 maintained the immune regulatory ability in airway M2 cells. SETD2 plays an important role in the maintenance of immune regulatory property of airway Mφs.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"185-195"},"PeriodicalIF":4.9,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of GPR56 reflects a hypoactivated state of circulating B cells and is downregulated in B cell subsets in patients with early-stage lung adenocarcinoma","authors":"Ayibaota Bahabayi,&nbsp;Zhao Guan,&nbsp;Mohan Zheng,&nbsp;He Yu,&nbsp;Ainizati Hasimu,&nbsp;Yuying Nie,&nbsp;Ming Zhao,&nbsp;Yaoyi Zhu,&nbsp;Jiaxin Ren,&nbsp;Yiming Zhao,&nbsp;Xiancan Ma,&nbsp;Qi Li,&nbsp;Zhonghui Zhang,&nbsp;Xingyue Zeng,&nbsp;Chen Liu","doi":"10.1111/imm.13819","DOIUrl":"10.1111/imm.13819","url":null,"abstract":"<p>Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer, and the early detection and diagnosis of this disease are crucial in reducing mortality rates. The timely diagnosis of LUAD is essential for controlling tumour development and enabling early surgical treatment. GPR56 is a vital G protein-coupled receptor and its role in T lymphocytes has received considerable attention. However, its function in B cells remains unclear. This study aimed to investigate the significance of GPR56 in LUAD. We found that GPR56 exhibited a significant increase in circulating plasmablasts and a decrease in new memory B cells. GPR56 expression in B cells was significantly reduced after LPS stimulation and the proportion of HLA-DR+ and CD40+ proportions were also decreased in GPR56+ B cells after stimulation. Additionally, GPR56 exhibited significant down-regulation in circulating B cell subsets of early-stage LUAD patients, and there were significant correlations between GPR56+ B cell subsets and tumour markers. In conclusion, GPR56 could reflect the hypoactivation state of B cells and the decreased proportion of GPR56+ B cell subset in LUAD patients can signify the active humoral immunity in vivo. The expression of GPR56 in B cells could potentially hold value in the early diagnosis of LUAD.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"172-184"},"PeriodicalIF":4.9,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impairment of Gal-9 and Tim-3 crosstalk between Tregs and Th17 cells drives tobacco smoke-induced airway inflammation","authors":"Shilin Qiu,&nbsp;Guang Zhou,&nbsp;Junyi Ke,&nbsp;Jianpeng Zhou,&nbsp;Hui Zhang,&nbsp;Zhitao Jin,&nbsp;Wenli Xie,&nbsp;Shu Huang,&nbsp;Zaiqin He,&nbsp;Huajiao Qin,&nbsp;Hui Huang,&nbsp;Qiuming Li,&nbsp;Hongchun Huang,&nbsp;Haijuan Tang,&nbsp;Yi Liang,&nbsp;Minchao Duan","doi":"10.1111/imm.13820","DOIUrl":"10.1111/imm.13820","url":null,"abstract":"<p>Overexpression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells has been observed in smokers. However, whether and how galectin-9 (Gal-9)/TIM-3 signal between T-regulatory cells (Tregs) and type 17 helper (Th17) cells contributes to tobacco smoke-induced airway inflammation remains unclear. Here, we aimed to explore the role of the Gal-9/TIM-3 signal between Tregs and Th17 cells during chronic tobacco smoke exposure. Tregs phenotype and the expression of TIM-3 on CD4⁺ T cells were detected in a mouse model of experimental emphysema. The role of TIM-3 in CD4⁺ T cells was explored in a HAVCR2^−/− mouse model and in mice that received recombinant anti-TIM3. The crosstalk between Gal-9 and Tim-3 was evaluated by coculture Tregs with effector CD4⁺ T cells. We also invested the expression of Gal-9 in Tregs in patients with COPD. Our study revealed that chronic tobacco smoke exposure significantly reduces the frequency of Tregs in the lungs of mice and remarkably shapes the heterogeneity of Tregs by downregulating the expression of Gal-9. We observed a pro-inflammatory but restrained phenotypic transition of CD4⁺ T cells after tobacco smoke exposure, which was maintained by TIM-3. The restrained phenotype of CD4⁺ T cells was perturbed when TIM-3 was deleted or neutralised. Tregs from the lungs of mice with emphysema displayed a blunt ability to inhibit the differentiation and proliferation of Th17 cells. The inhibitory function of Tregs was partially restored by using recombinant Gal-9. The interaction between Gal-9 and TIM-3 inhibits the differentiation of Th17 cells and promotes apoptosis of CD4⁺ T cells, possibly by interfering with the expression of retinoic acid receptor-related orphan receptor gamma t. The expression of Gal-9 in Tregs was reduced in patients with COPD, which was associated with Th17 response and lung function. These findings present a new paradigm that impairment of Gal-9/Tim-3 crosstalk between Tregs and Th17 cells during chronic tobacco smoke exposure promotes tobacco smoke-induced airway/lung inflammation.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"152-171"},"PeriodicalIF":4.9,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icariin alleviates oxygen-induced retinopathy by targeting microglia hexokinase 2","authors":"Xingran Li,&nbsp;Guoqing Wang,&nbsp;Na Li,&nbsp;Xiaotang Wang,&nbsp;Wei Fan,&nbsp;Zhi Zhang,&nbsp;Wanqian Li,&nbsp;Jiangyi Liu,&nbsp;Jiaxing Huang,&nbsp;Xianyang Liu,&nbsp;Qian Zhou,&nbsp;Shengping Hou","doi":"10.1111/imm.13818","DOIUrl":"10.1111/imm.13818","url":null,"abstract":"<p>Retinopathy of prematurity (ROP) is a retinal disease-causing retinal neovascularization that can lead to blindness. Oxygen-induced retinopathy (OIR) is a widely used ROP animal model. Icariin (ICA) has anti-oxidative and anti-inflammation properties; however, whether ICA has a regulatory effect on OIR remains unclear. In this study, ICA alleviated pathological neovascularization, microglial activation and blood–retina barrier (BRB) damage in vivo. Further results indicated that endothelial cell tube formation, migration and proliferation were restored by ICA treatment in vitro. Proteomic microarrays and molecular mimicry revealed that ICA can directly bind to hexokinase 2 (HK2) and decrease HK2 protein expression in vivo and in vitro. In addition, ICA inhibited the AKT/mTOR/HIF1α pathway activation. The effects of ICA on pathological neovascularization, microglial activation and BRB damage disappeared after HK2 overexpression in vivo. Similarly, the endothelial cell function was revised after HK2 overexpression. HK2 overexpression reversed ICA-induced AKT/mTOR/HIF1α pathway inhibition in vivo and in vitro. Therefore, ICA prevented pathological angiogenesis in OIR in an HK2-dependent manner, implicating ICA as a potential therapeutic agent for ROP.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"141-151"},"PeriodicalIF":4.9,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A unique human cord blood CD8+CD45RA+CD27+CD161+ T-cell subset identified by flow cytometric data analysis using Seurat","authors":"Julen Gabirel Araneta Reyes,&nbsp;Duan Ni,&nbsp;Brigitte Santner-Nanan,&nbsp;Gabriela Veronica Pinget,&nbsp;Lucie Kraftova,&nbsp;Thomas Myles Ashhurst,&nbsp;Felix Marsh-Wakefield,&nbsp;Claire Leana Wishart,&nbsp;Jian Tan,&nbsp;Peter Hsu,&nbsp;Nicholas Jonathan Cole King,&nbsp;Laurence Macia,&nbsp;Ralph Nanan","doi":"10.1111/imm.13803","DOIUrl":"10.1111/imm.13803","url":null,"abstract":"<p>Advances in single-cell level analytical techniques, especially cytometric approaches, have led to profound innovation in biomedical research, particularly in the field of clinical immunology. This has resulted in an expansion of high-dimensional data, posing great challenges for comprehensive and unbiased analysis. Conventional manual analysis is thus becoming untenable to handle these challenges. Furthermore, most newly developed computational methods lack flexibility and interoperability, hampering their accessibility and usability. Here, we adapted Seurat, an R package originally developed for single-cell RNA sequencing (scRNA-seq) analysis, for high-dimensional flow cytometric data analysis. Based on a 20-marker antibody panel and analyses of T-cell profiles in both adult blood and cord blood (CB), we showcased the robust capacity of Seurat in flow cytometric data analysis, which was further validated by Spectre, another high-dimensional cytometric data analysis package, and conventional manual analysis. Importantly, we identified a unique CD8⁺ T-cell population defined as CD8⁺CD45RA⁺CD27⁺CD161⁺ T cell that was predominantly present in CB. We characterised its IFN-γ-producing and potential cytotoxic properties using flow cytometry experiments and scRNA-seq analysis from a published dataset. Collectively, we identified a unique human CB CD8⁺CD45RA⁺CD27⁺CD161⁺ T-cell subset and demonstrated that Seurat, a widely used package for scRNA-seq analysis, possesses great potential to be repurposed for cytometric data analysis. This facilitates an unbiased and thorough interpretation of complicated high-dimensional data using a single analytical pipeline and opens a novel avenue for data-driven investigation in clinical immunology.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"106-124"},"PeriodicalIF":4.9,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13803","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}