European Journal of Immunology最新文献_第9页

Tissue-Resident Memory and Follicular/Peripheral Helper PD-1+ T Cells Infiltrate Lesional Skin in Atopic Dermatitis 组织驻留记忆和滤泡/外周辅助PD-1+ T细胞浸润病变皮肤的特应性皮炎

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-19 DOI: 10.1002/eji.202551820

Heena Mehta, Léane Pellerin, Manuel Rubio, Catherine Maari, Étienne S. Proulx, Sharan Nischal, Vaishali R. Moulton, Monica W. L. Leung, Robert Bissonnette, Marika Sarfati

{"title":"Tissue-Resident Memory and Follicular/Peripheral Helper PD-1+ T Cells Infiltrate Lesional Skin in Atopic Dermatitis","authors":"Heena Mehta, Léane Pellerin, Manuel Rubio, Catherine Maari, Étienne S. Proulx, Sharan Nischal, Vaishali R. Moulton, Monica W. L. Leung, Robert Bissonnette, Marika Sarfati","doi":"10.1002/eji.202551820","DOIUrl":"https://doi.org/10.1002/eji.202551820","url":null,"abstract":"Atopic dermatitis (AD) is primarily driven by Th2 cells. Although CD3+ T cells and CD11c+ cells predominate in lesional (L) over nonlesional (NL) skin, both sites harbor epidermal dysregulation and a type 2 profile relative to healthy skin. Therapeutics focusing on Th2-mediated pathways partially fill an unmet medical need, highlighting the importance of further characterizing the adaptive and innate immune landscape in L versus NL skin. Paired L and NL biopsies and matched blood samples were collected from 10 patients. The immunophenotype and cytokine profile of immune cells were examined at the single-cell level using multiparameter flow cytometry and unsupervised analysis. L compared with NL skin was predominantly infiltrated by CD4+CD103+PD-1+ tissue-resident memory T cells (TRMs) that positively correlated with disease severity (EASI). CD4+ CD103+PD-1+ TRMs coexpressed CD25 and ICOS. Frequencies of skin-resident CD4+CD103−PD-1+CXCR5+CCR5+/− follicular/peripheral helper T cells (Tfh/Tph) were also augmented in L skin. CCR5− Tfh/Tph coexpressed ICOS, OX40, and IFN-γ along with IL-4 or CD120b while CCR5+ Tfh/Tph coexpressed IL-4Rα. Furthermore, inflammatory monocytes and monocyte-derived dendritic cells (Mo-DCs) positively correlated with CD4+CD103+PD-1+ TRMs and EASI in L skin. These findings enhance our knowledge of AD's innate and adaptive immune profile which may facilitate the discovery of novel therapeutic targets.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202551820","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314959","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}

引用次数: 0

IL-4, IL-15, and Type I Interferon Orchestrate the Shaping of the Heterogeneity of Virtual Memory CD8 T Cells IL-4、IL-15和I型干扰素协调虚拟记忆CD8 T细胞异质性的形成

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-18 DOI: 10.1002/eji.202451765

Hi Jung Park, Sung Min Choi, Eun A. Choi, Hyun Ji Boo, Jae Il Lee, Kyeong Cheon Jung

{"title":"IL-4, IL-15, and Type I Interferon Orchestrate the Shaping of the Heterogeneity of Virtual Memory CD8 T Cells","authors":"Hi Jung Park, Sung Min Choi, Eun A. Choi, Hyun Ji Boo, Jae Il Lee, Kyeong Cheon Jung","doi":"10.1002/eji.202451765","DOIUrl":"https://doi.org/10.1002/eji.202451765","url":null,"abstract":"The development of virtual memory CD8 T cells is dependent on IL-4, type I interferon, and IL-15. However, it remains unclear whether these cytokines individually contribute to the generation of specific subsets of virtual memory CD8 T cells. In this study, virtual memory CD8 T cells were categorized into four subsets based on Ly6C and Sca-1 expression, and their development was examined using knock-out mice lacking IFNAR1, IL-4, or IL-15Rα. Notably, both Ly6C+ Sca-1+ and Ly6C− Sca-1+ subsets were significantly reduced in the spleen of IFNAR1 knock-out mice, while the proportion of Ly6C+ Sca-1− VM CD8 T cells was reduced in IL-4-deficient mice. In IL-15Rα knock-out mice, both the Ly6C+ Sca-1− and Ly6C- Sca-1− subsets were significantly reduced. Bulk RNA sequencing analysis revealed distinct gene expression patterns in naïve cells, true memory cells, and the four virtual memory cell subsets. Specifically, Ly6C+ subsets were enriched with IL-15 signal-related genes, whereas Ly6C− subsets and true memory cells were enriched for cell cycle-related genes. Functionally, the Ly6C+ and/or Sca-1+ subsets exhibited higher production of IFN-γ and TNF-α compared with the Ly6C- Sca-1− subsets. Overall, this study demonstrates the heterogeneity of virtual memory CD8 T cells and highlights the cytokine-dependent nature of their development.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451765","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315133","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}

引用次数: 0

Resolution of Autoimmune Uveitis Requires CCL20-Dependent Regulatory T Cells 自身免疫性葡萄膜炎的解决需要依赖ccl20的调节性T细胞

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-11 DOI: 10.1002/eji.202551854

John Dostal, Kayleigh Peters, Trisha McDonald, Darren J. Lee

{"title":"Resolution of Autoimmune Uveitis Requires CCL20-Dependent Regulatory T Cells","authors":"John Dostal, Kayleigh Peters, Trisha McDonald, Darren J. Lee","doi":"10.1002/eji.202551854","DOIUrl":"https://doi.org/10.1002/eji.202551854","url":null,"abstract":"<div>\u0000 \u0000 Uveitis is a leading cause of blindness worldwide and regulatory T cells inversely correlate with uveitis. CCL20 is the chemokine that attracts cells expressing CCR6 and has been shown to be expressed on Tregs. Uveitis patients have a reduced capacity to generate CCR6-expressing Tregs. Using the experimental autoimmune uveitis (EAU) model we examined the effect of a CCL20 deficiency on EAU resolution and the induction and function of Tregs. This report demonstrates that a deficiency in CCL20 delays the resolution of EAU and inhibits the induction of Tregs associated with EAU resolution (post-EAU Tregs). Importantly, a CCL20 deficiency does not impact the capacity of post-EAU Tregs to suppress EAU. The impact of these observations is that if the deficiency preventing the induction of ocular Tregs can be bypassed these Tregs will still be able to function to provide lasting remission of uveitis. This study is the first demonstration that CCL20 is needed for the timely resolution of EAU, that it is required for the generation of post-EAU Tregs, and that CCL20 is not required for post-EAU Tregs to suppress disease, that is, CCL20 is needed for timely resolution of EAU and Treg induction but not function.\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264590","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}

引用次数: 0

Meningeal Immunity: Anatomy, Function, and Neonatal Unique Features 脑膜免疫：解剖、功能和新生儿的独特特征

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-11 DOI: 10.1002/eji.202451618

Inês Lorga, Elva Bonifácio Andrade

引用次数: 0

Identification and Mapping of Human Lymph Node Stromal Cell Subsets by Combining Single-Cell RNA Sequencing with Spatial Transcriptomics 结合单细胞RNA测序和空间转录组学，鉴定和定位人淋巴结基质细胞亚群

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-11 DOI: 10.1002/eji.202451218

Cristoforo Grasso, Janna E. G. Roet, Catarina Gago de Graça, Johanna F. Semmelink, Michael de Kok, Ester Remmerswaal, Aldo Jongejan, Perry D. Moerland, Reina E. Mebius, Lisa G. M. van Baarsen

{"title":"Identification and Mapping of Human Lymph Node Stromal Cell Subsets by Combining Single-Cell RNA Sequencing with Spatial Transcriptomics","authors":"Cristoforo Grasso, Janna E. G. Roet, Catarina Gago de Graça, Johanna F. Semmelink, Michael de Kok, Ester Remmerswaal, Aldo Jongejan, Perry D. Moerland, Reina E. Mebius, Lisa G. M. van Baarsen","doi":"10.1002/eji.202451218","DOIUrl":"https://doi.org/10.1002/eji.202451218","url":null,"abstract":"Lymph node stromal cells (LNSCs) have a crucial immunomodulatory function, but their heterogeneity in humans is incompletely understood. Here, we report the single-cell RNA sequencing (scRNA-seq) of 9267 LNSCs isolated from a human lymph node (LN). This study comprehensively defines the gene signatures of 10 fibroblast subtypes: CCL21+ SC, CCL19+ SC, CD34+CXCL14+ SC, pericytes, DES+ SC, LAMP5+ SC, NR4A1+BCAM+ SC, HLA-DR+ SC, SEPT4+ SC and GLDN+ SC. The existence of these subtypes was validated across 13 LN donors using 2 publicly available datasets and our dataset. To explore the heterogeneous stromal compartment within the complex LN tissue architecture, we integrated the scRNA-seq profiles of the identified LNSC subsets with a publicly available human spatial transcriptomic LN dataset and predicted their location within the complex LN tissue architecture. Each LNSC subtype was spatially restricted to specific LN regions, indicating different LNSC–lymphocyte interactions, which were further investigated using NicheNet. The positioning of distinct LNSC subtypes within different LN regions sets the stage for future research on the relationship between LNSC-specific niches and immunomodulatory function during health and disease.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451218","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264591","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}

引用次数: 0

Dipeptidyl Peptidase 9 in Human Leukocytes: Novel Inhibitors Induce Caspase-1- and Gasdermin-Dependent Cell Death 人白细胞中的二肽基肽酶9：新型抑制剂诱导Caspase-1和气真皮蛋白依赖性细胞死亡

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-11 DOI: 10.1002/eji.202451526

Joni De Loose, Kathleen Mertens, Nicolò Filippi, Sam Corthaut, Siham Benramdane, Yani Sim, Yentl Van Rymenant, Karen Claesen, Gwendolyn Vliegen, Maya Berg, Tiphanie Gomard, Guy Caljon, Isabel Pintelon, Pieter Van Der Veken, Ingrid De Meester

{"title":"Dipeptidyl Peptidase 9 in Human Leukocytes: Novel Inhibitors Induce Caspase-1- and Gasdermin-Dependent Cell Death","authors":"Joni De Loose, Kathleen Mertens, Nicolò Filippi, Sam Corthaut, Siham Benramdane, Yani Sim, Yentl Van Rymenant, Karen Claesen, Gwendolyn Vliegen, Maya Berg, Tiphanie Gomard, Guy Caljon, Isabel Pintelon, Pieter Van Der Veken, Ingrid De Meester","doi":"10.1002/eji.202451526","DOIUrl":"https://doi.org/10.1002/eji.202451526","url":null,"abstract":"<div>\u0000 \u0000 Dipeptidyl peptidase 9 (DPP9) is an intracellular serine protease with key roles in the immune response. In human leukocytes, DPP9 interacts with caspase recruitment domain-containing protein 8 (CARD8) to form an inhibitory complex that prevents spontaneous inflammation. Inhibition or depletion of DPP9 activates CARD8 inflammasome signaling and triggers lytic cell death. Here, we examined the effects of two novel DPP9-targeting inhibitors, cpd-42 and cpd-6a, on the viability of human leukocytes. Both compounds induced dose-dependent lytic cell death in myeloid leukemia cell lines without a concurrent increase in IL-1β or IL-18 secretion. We confirmed that DPP9, caspase-1, gasdermin D (GSDMD) and gasdermin E (GSDME) contribute to the cell death observed with cpd-42 and cpd-6a. In addition, both inhibitors triggered lytic cell death in isolated human monocytes, monocyte-derived macrophages, monocyte-derived dendritic cells, and T cells, with activated T cells showing the lowest sensitivity. Examination of DPP activity revealed upregulation of DPP8/9 activity upon dendritic cell differentiation. Lastly, we found that DPP9 can localize to both the cytoplasm and the nucleus of isolated human leukocytes, warranting further evaluation of DPP9's nuclear roles.\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264647","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}

引用次数: 0

Comparative Analysis of the TCR Repertoire in Bone Marrow CD8+ T Cells From Patients With Acute Myeloid Leukemia, Myelodysplastic Neoplasms, and Chronic Myelomonocytic Leukemia 急性髓系白血病、骨髓增生异常肿瘤和慢性髓单细胞白血病患者骨髓CD8+ T细胞TCR库的比较分析

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-11 DOI: 10.1002/eji.202551796

Kyriaki Katsiki, Athanasios Tasis, Anastasia Filia, Ioannis Kotsianidis, Ioannis Mitroulis

引用次数: 0

The Complex Role of CD8+ T Cells in Placental HIV Infection CD8+ T细胞在胎盘HIV感染中的复杂作用

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-11 DOI: 10.1002/eji.202451615

Kimberly Peta, Mushi Matjila, Nadia Ikumi

{"title":"The Complex Role of CD8+ T Cells in Placental HIV Infection","authors":"Kimberly Peta, Mushi Matjila, Nadia Ikumi","doi":"10.1002/eji.202451615","DOIUrl":"https://doi.org/10.1002/eji.202451615","url":null,"abstract":"The global HIV epidemic presents ongoing challenges, particularly in Sub-Saharan Africa, where women of reproductive age are disproportionately affected. Despite strides in prevention strategies, maternal HIV infection continues to impact pregnancy outcomes. This review delves into the complex interplay between HIV and CD8+ T cells at the maternal-fetal interface, elucidating their roles in viral transmission and pregnancy. Maternal HIV infection introduces complexities to pregnancy, elevating the risk of adverse outcomes such as miscarriage, stillbirth, and low birth weight deliveries. The placenta, a multifunctional organ crucial for maternal–fetal exchange, serves as a site for intricate immunological interactions during HIV infection. Despite its protective mechanisms, HIV can exploit vulnerabilities, such as cell-to-cell transmission and Hofbauer cells expressing CD4 receptors, within the placenta. CD8+ T cells, as key effectors of the antiviral immune response, play a pivotal role in combating HIV within this environment. However, their precise efficacy against HIV-1 within the placenta remains unclear. This review underscores the urgent need for a comprehensive understanding of CD8+ T cell dynamics in pregnancy-related HIV infections within the placenta. Understanding the complex interactions between HIV, CD8+ T cells, and the placenta is crucial for elucidating their roles in maintaining a balanced immune response during pregnancy, thereby safeguarding the health and well-being of both mother and child.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451615","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264595","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}

引用次数: 0

5-ALA Assisted Surgery of Human Glioblastoma Samples Reveals an Enrichment of T Cells Expressing PD-1 and CD103 in the Intermediate and Marginal Layers 5-ALA辅助手术治疗人类胶质母细胞瘤样本发现在中间层和边缘层表达PD-1和CD103的T细胞富集

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-11 DOI: 10.1002/eji.202451681

Anna Vanni, Francesca Matani, Camilla Bonaudo, Alessio Mazzoni, Manuela Capone, Giulia Lamacchia, Lorenzo Salvati, Lucia Bartoli, Stefania Francalanci, Mirko Petti, Federico Capelli, Filippo Nozzoli, Lorenzo Cosmi, Francesco Liotta, Alessandro Della Puppa, Laura Maggi, Francesco Annunziato

{"title":"5-ALA Assisted Surgery of Human Glioblastoma Samples Reveals an Enrichment of T Cells Expressing PD-1 and CD103 in the Intermediate and Marginal Layers","authors":"Anna Vanni, Francesca Matani, Camilla Bonaudo, Alessio Mazzoni, Manuela Capone, Giulia Lamacchia, Lorenzo Salvati, Lucia Bartoli, Stefania Francalanci, Mirko Petti, Federico Capelli, Filippo Nozzoli, Lorenzo Cosmi, Francesco Liotta, Alessandro Della Puppa, Laura Maggi, Francesco Annunziato","doi":"10.1002/eji.202451681","DOIUrl":"https://doi.org/10.1002/eji.202451681","url":null,"abstract":"Glioblastoma is the most common malignant brain tumor in adults, for which immunotherapy shows reduced efficacy. Current knowledge on immunotherapy failure is limited and detailed information about immune infiltrates in glioblastoma is urgently needed. We enrolled 34 glioblastoma patients collecting peripheral blood (PB), total tumor resection, or tumor from the necrotic area, the intermediate, and the marginal tissue through 5-aminolevulinic-acid (5-ALA) assisted surgery. T cells were evaluated for immune checkpoints and tissue residence memory (Trm) cell markers expression, and their cytokine production profile. Biological data were correlated with the patient's overall survival. Flow cytometry analysis showed a significantly higher frequency of T lymphocytes expressing PD-1, Trm markers in glioblastoma than in PB. In particular, we observed a preferential enrichment of CD8 cells expressing PD-1 and Trm markers in the intermediate and marginal tissue. T cells cytokine production resulted in increased glioblastoma compared with PB, in particular in PD-1+ cells and in the intermediate and marginal layers. These data suggest that CD103+ T-cell frequency in the core and TNF-a+CD8+ T cells in the intermediate layer influence the patient's survival. In conclusion, T cells obtained from different GBM layers showed different phenotypes and cytokines expression, suggesting new prognostic factors and supporting surgery particle strategy.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451681","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264588","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}

引用次数: 0

Pro- and Anti-Inflammatory Role of Complement in Cancer 补体在癌症中的促炎作用

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-11 DOI: 10.1002/eji.202451767

Pradipta Pal, Praneet Wahi, Arvind Sahu, Girdhari Lal

引用次数: 0