European Journal of Immunology最新文献

Remote Force Modulation of the T-Cell Receptor Reveals an NFAT-Threshold for CD4+ T-Cell Activation t细胞受体的远程力调节揭示了CD4+ t细胞激活的nfat阈值

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-24 DOI: 10.1002/eji.202451716

Joseph Clarke, Jeremy Pike, David Bending, Dylan Owen, David C. Wraith, Alicia J. El Haj

{"title":"Remote Force Modulation of the T-Cell Receptor Reveals an NFAT-Threshold for CD4+ T-Cell Activation","authors":"Joseph Clarke, Jeremy Pike, David Bending, Dylan Owen, David C. Wraith, Alicia J. El Haj","doi":"10.1002/eji.202451716","DOIUrl":"https://doi.org/10.1002/eji.202451716","url":null,"abstract":"Mechano-modulation of cell surface proteins to influence cell activation has been shown as a promising new advanced therapy for regenerative medicine applications. These strategies rely on the manipulation of mechanosensitive cell surface receptors to initiate intracellular signal transduction. The cell surface receptor of T lymphocytes (TCR), which recognises peptide-MHC molecules central to driving the adaptive immune response, has recently been suggested to be mechano-responsive. Despite this advance, little is known as to whether the TCR can be mechanically modulated to achieve TCR signalling and subsequent T-cell activation, and whether these characteristics can be exploited for immunotherapies. Here, we describe a magnetic particle-based platform for mechanical modulation of the TCR and outline how this platform can be utilised to achieve CD4+ T-cell activation. We demonstrate that mechanical manipulation of the TCR induces cell surface clustering of the TCR and downstream TCR signalling, leading to eventual TCR downregulation and T-cell activation. We investigate the temporal relationship between mechanical modulation of the TCR and subsequent T-cell activation, thereby identifying that accumulation of signalling events within the NFAT pathway is required to reach the threshold required for CD4+ T-cell activation, outlining an axis which controls the CD4+ T-cell response to external mechanical cues. These findings identify how CD4+ T cells can modulate their function in response to such cues while also outlining a remote-magnetic particle-based platform that may be used for the control of T-cell responses.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451716","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473166","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

γδ T Cells and Inborn Errors of Immunity γδ T细胞与先天性免疫错误

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-24 DOI: 10.1002/eji.202451457

Sagar, Stephan Ehl

引用次数: 0

Biological Sex Influences Human Bystander CD8+ T Cell Activation 生物性别影响人类旁观者CD8+ T细胞激活

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-24 DOI: 10.1002/eji.202451673

Elizabeth Balint, Marie Joe Adaimy, Amelia Montemarano, Ana L. Portillo, Ali A. Ashkar

{"title":"Biological Sex Influences Human Bystander CD8+ T Cell Activation","authors":"Elizabeth Balint, Marie Joe Adaimy, Amelia Montemarano, Ana L. Portillo, Ali A. Ashkar","doi":"10.1002/eji.202451673","DOIUrl":"https://doi.org/10.1002/eji.202451673","url":null,"abstract":"<div>\u0000 \u0000 The recent COVID-19 pandemic has highlighted a significant sex bias in disease outcome, where male sex is associated with greater disease severity and mortality. Interestingly, studies have also identified a role for antigen-independent “bystander-activated” CD8+ T cells in the severity of COVID-19 and other viral infections. However, whether biological sex contributes to the magnitude of bystander T cell activation has not been investigated. To assess sex differences in bystander CD8+ T cell activation, we isolated PBMCs from age-matched male and female donors and stimulated the cells with cytokines IL-12/15/18 to induce bystander T cell activation. Male CD8+ T cells stimulated with IL-15 exhibited greater bystander activation, including increased NKG2D expression and greater antigen-independent cytotoxicity against tumor cells compared with female CD8+ T cells. In contrast, IL-12/18 and IL-12/15/18 stimulation of CD8+ T cells did not reveal evidence of sex differences in bystander IFN-γ production. Our data suggest that underlying sex differences in bystander CD8+ T cell activation and cytotoxicity may contribute to the observed sex biases in disease severity of viral infections.\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367423","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

The Frequency but not the Phenotype of Circulating Peripheral T Helper Cells is Increased at Later Stages of Progression to Type 1 Diabetes 循环外周辅助性T细胞的频率在1型糖尿病晚期增加，而非表型增加

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-20 DOI: 10.1002/eji.202451704

Anna-Mari Schroderus, Andrea Hanel, Céline Vandamme, Viola Pitkänen, Marja Rytkönen-Nissinen, Merja Heinäniemi, Mikael Knip, Riitta Veijola, Jorma Toppari, Jorma Ilonen, Johanna Lempainen, Tuure Kinnunen

{"title":"The Frequency but not the Phenotype of Circulating Peripheral T Helper Cells is Increased at Later Stages of Progression to Type 1 Diabetes","authors":"Anna-Mari Schroderus, Andrea Hanel, Céline Vandamme, Viola Pitkänen, Marja Rytkönen-Nissinen, Merja Heinäniemi, Mikael Knip, Riitta Veijola, Jorma Toppari, Jorma Ilonen, Johanna Lempainen, Tuure Kinnunen","doi":"10.1002/eji.202451704","DOIUrl":"https://doi.org/10.1002/eji.202451704","url":null,"abstract":"Circulating follicular (cTfh) and peripheral (cTph) T helper cells have been demonstrated to be expanded in several autoimmune diseases, including type 1 diabetes (T1D). Here, we examined the frequencies and phenotypes of these cells at different stages of T1D development and addressed their phenotypic and clonal relationships by analyzing samples from 27 children with newly diagnosed T1D, 29 autoantibody-positive (AAb+) children who later progressed to T1D and 57 healthy, age-matched controls. Higher frequencies of cTph cells were detected in children with T1D and AAb+ children by flow cytometry, but no phenotypic alterations compared with cTph cells from healthy children were observed. Through a single-cell multiomics approach, we demonstrate that cTph cells appear phenotypically more heterogeneous compared with cTfh cells and that they exhibit phenotypic and clonal sharing with both cTfh as well as CXCR5−PD-1lo memory T cells. Finally, the frequencies of cTph or cTfh cells did not differ in 17 children analyzed during seroconversion for T1D-associated autoantibodies, the earliest detectable time point for autoimmunity. Collectively, our data demonstrate that cTph cells are a highly heterogeneous population partially sharing features with cTfh cells and that their frequency but not phenotype is altered at later stages of progression to clinical T1D.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451704","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323445","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

NKG7 is a Stable Marker of Cytotoxicity Across Immune Contexts and Within the Tumor Microenvironment NKG7是免疫环境和肿瘤微环境中细胞毒性的稳定标志物

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-20 DOI: 10.1002/eji.202551885

Roberta Turiello, Susanna S. Ng, Elisabeth Tan, Gemma van der Voort, Nazhifah Salim, Michelle C. R. Yong, Malika Khassenova, Johannes Oldenburg, Heiko Rühl, Jan Hasenauer, Laura Surace, Marieta Toma, Tobias Bald, Michael Hölzel, Dillon Corvino

{"title":"NKG7 is a Stable Marker of Cytotoxicity Across Immune Contexts and Within the Tumor Microenvironment","authors":"Roberta Turiello, Susanna S. Ng, Elisabeth Tan, Gemma van der Voort, Nazhifah Salim, Michelle C. R. Yong, Malika Khassenova, Johannes Oldenburg, Heiko Rühl, Jan Hasenauer, Laura Surace, Marieta Toma, Tobias Bald, Michael Hölzel, Dillon Corvino","doi":"10.1002/eji.202551885","DOIUrl":"https://doi.org/10.1002/eji.202551885","url":null,"abstract":"Cytotoxicity is a cornerstone of immune defense, critical for combating tumors and infections. This process relies on the coordinated action of granzymes and pore-forming proteins, with granzyme B (GZMB) and perforin (PRF1) being key markers and the most widely studied molecules pertaining to cytotoxicity. However, other human granzymes and cytotoxic components remain underexplored, despite growing evidence of their distinct, context-dependent roles. Natural killer cell granule protein 7 (NKG7) has recently emerged as a crucial cytotoxicity regulator, yet its expression patterns and function are poorly understood. Using large publicly available single-cell RNA sequencing atlases, we performed a comprehensive profiling of cytotoxicity across immune subsets and tissues. Our analysis highlights NKG7 expression as a strong marker of cytotoxicity, exhibiting a strong correlation with overall cytotoxic activity (r = 0.97) and surpassing traditional markers such as granzyme B and perforin in reliability. Furthermore, NKG7 expression is notably consistent across diverse immune subsets and tissues, reinforcing its versatility and robustness as a cytotoxicity marker. These findings position NKG7 as an invaluable tool for evaluating immune responses and a reliable indicator of cytotoxic functionality across biological and clinical contexts.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202551885","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323415","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

Narrowing Down Key Players in Autoimmunity via Single-Cell Multiomics 通过单细胞多组学缩小自身免疫的关键参与者

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-06-19 DOI: 10.1002/eji.202451233

Altea Gjurgjaj, Cecilia Domínguez Conde

引用次数: 0

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