European Journal of Immunology最新文献

{"title":"Influence of SLAM Family Receptors in the NK-Cell-Mediated Surveillance of Lymphoblastic Acute Leukemia","authors":"Jacqueline Sánchez-Herrera,&nbsp;Lucero Valenzuela-Vázquez,&nbsp;Juan Carlos Nuñez-Enriquez,&nbsp;Fernando Arellano-Juvera,&nbsp;Elva Jiménez-Hernandéz,&nbsp;Minerva Mata-Rocha,&nbsp;Janet Flores-Lujano,&nbsp;José Gabriel Peñaloza-Gonzalez,&nbsp;César Alejandro Galván-Díaz,&nbsp;José Refugio Torres-Nava,&nbsp;Jorge Alfonso Martín-Trejo,&nbsp;María de Lourdes Gutiérrez-Rivera,&nbsp;Rosa Martha Espinosa-Elizondo,&nbsp;Laura Elizabeth Merino-Pasaye,&nbsp;Maria Luisa Pérez-Saldívar,&nbsp;Luz Victoria Flores-Villegas,&nbsp;Karina Anastacia Solís-Labastida,&nbsp;María Raquel Miranda-Madrazo,&nbsp;Gabriela Alicia Hernández-Echáurregui,&nbsp;Darío Orozco-Ruíz,&nbsp;Aurora Medina-Sanson,&nbsp;Omar Alejandro Sepúlveda-Robles,&nbsp;Haydeé Rosas-Vargas,&nbsp;Ismael Mancilla-Herrera,&nbsp;Luis R. Rodríguez-Villalobos,&nbsp;Juan José Dosta-Herrera,&nbsp;Javier A. Mondragón-García,&nbsp;Alejandro Castañeda-Echevarría,&nbsp;M. Guadalupe López-Caballero,&nbsp;Sofía I. Martínez-Silva,&nbsp;Juan Rivera-González,&nbsp;Norma A. Hernández-Pineda,&nbsp;Jesús Flores-Botello,&nbsp;Jessica A. Pérez-Gómez,&nbsp;M. Adriana Rodríguez-Vázquez,&nbsp;Delfino Torres-Valle,&nbsp;Jaime Á. Olvera-Durán,&nbsp;Annel Martínez-Ríos,&nbsp;Luis R. García-Cortés,&nbsp;Carolina Almeida-Hernández,&nbsp;Vilma Carolina Bekker-Méndez,&nbsp;Leila Vera-Ramirez,&nbsp;Oscar Zamudio-Chávez,&nbsp;Ivan Martínez-Duncker,&nbsp;Kevin P. Madauss,&nbsp;Jorge Meléndez-Zajgla,&nbsp;André Veillette,&nbsp;Juan Manuel Mejía-Arangure,&nbsp;Mario Ernesto Cruz-Muñoz","doi":"10.1002/eji.70014","DOIUrl":"https://doi.org/10.1002/eji.70014","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer worldwide. Along with other lymphocytes, NK cells have important functions in the recognition and elimination of malignant cells, and thus are of interest for the development of novel therapeutic treatments of various cancers, including leukemia. The signaling lymphocyte activation molecule (SLAM) family includes surface molecules that are expressed in hematopoietic cells, where they regulate distinct cell responses. Altered expression and/or function of these receptors may be involved in the etiology of several diseases. Here we report the altered overall expression of SLAM family receptors (SFR) in leukemia cells from pediatric patients. Additionally, we found that the expression of a single type of SLAM receptor in leukemia target cells was sufficient to upregulate the release of cytotoxic granules from primary NK cells. Moreover, coating the leukemia cell surface with specific engagers containing recombinant SFR was sufficient to enhance NK-cell degranulation and unleash the cytotoxic competence of primary NK cells from ALL patients. Finally, the NK effector responses promoted by SLAM receptor engagement were dependent on the ability to recruit PLC-γ. Overall, these findings suggest that SFR are a promising resource for the treatment of pediatric acute lymphoblastic leukemia.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767328","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":"Exploring How Cytoskeleton Dynamics Tunes T Cell Activation at the Immunological Synapse.","authors":"Álvaro Gómez-Morón, Adrián González-Pinar, Carlos Carrasco-Padilla, Pedro Roda-Navarro, Noa Beatriz Martín-Cófreces","doi":"10.1002/eji.70028","DOIUrl":"https://doi.org/10.1002/eji.70028","url":null,"abstract":"<p><p>During T cell immune responses, actin dynamics facilitates the scanning of antigen-presenting cells (APCs) and the antigen engagement by the T cell receptor (TCR), initiating activation. This activation, in turn, promotes further cytoskeletal rearrangements, leading to the formation of a specialized T cell/APC adhesion structure known as the immunological synapse (IS). Actin and tubulin dynamics at the IS sustain activating signals by generating forces that activate signaling molecules and integrins while polarizing the centrosome and the endosomal compartment toward the IS center. The polarized endosomal compartment delivers signaling molecules and activating receptors to the activation site, along with secretory vesicles, during the effector phase. Thus, the IS is essential for full T cell activation and effector function. Regulation of cytoskeleton rearrangements relies on a network of signaling molecules and cytoskeleton-regulatory proteins tightly controlled in space and time. In this review, we examine the roles of key regulators, such as SSH1 phosphatase and LIMK1, in actin and tubulin dynamics and discuss the relevance of mechanotransduction in T cell activation.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":"e70028"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793093","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":"Granulysin Antimicrobial Activity Promotes Dormancy in Mycobacterium tuberculosis.","authors":"Sarah Schmidiger, Erin F McCaffrey, Jan M Schmidt, Owais Abdul Hameed, Max Mpina, Anneth Tumbo, Elirehema Mfinanga, Frederick Haraka, Hellen Hiza, Mohamed Sasamalo, Jerry Hella, Michael Walch, Jacques Fellay, Sébastien Gagneux, Klaus Reither, José M Carballido, Ainhoa Arbués, Damien Portevin","doi":"10.1002/eji.70004","DOIUrl":"10.1002/eji.70004","url":null,"abstract":"<p><p>Human tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains a global public health threat. Granulomas constitute a hallmark of TB pathogenesis that can clear, contain, or exacerbate an infection. Containment is exploited by Mtb as a hideout to persist in a dormant, antibiotic-tolerant state, only to resuscitate upon immunosuppression. The immune determinants of a granulomatous response driving Mtb persistence remain elusive. We here generated ex vivo granuloma-like structures from peripheral blood mononuclear cell specimens of TB patients and applied high-dimensional mass cytometry to elucidate immune factors prompting Mtb dormancy. Compared with healthy controls, patient-derived specimens rapidly forced Mtb to become dormant-like ex vivo. This observation correlated with an enrichment in activated, innate (-like) cytotoxic lymphocytes and required the presence of CD56⁺ lymphocytes or, more specifically, the content of their granules. Finally, we demonstrated that direct exposure to granulysin induces Mtb dormancy, thereby unravelling an immune escape mechanism to cytotoxic lymphocyte activity.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":"e70004"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797741","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":"Suppressor of Cytokine Signaling Mimetics as a Therapeutic Approach in Autoimmune Encephalitis.","authors":"Rahul Pandey, Marina Bakay, Hakon Hakonarson","doi":"10.1002/eji.70023","DOIUrl":"https://doi.org/10.1002/eji.70023","url":null,"abstract":"<p><p>Autoimmune encephalitis (AE) is a debilitating neurological condition characterized by the immune system's attack on neuronal cells, often leading to significant cognitive and neurological impairments. Autoantibodies, particularly those targeting N-methyl-D-aspartate receptors (NMDAR), are linked to the disease. Additionally, cytokine dysregulation has been associated with heightened inflammatory responses in AE. Early intervention is critical for favorable outcomes. Recent findings have underscored the importance of suppressor of cytokine signaling (SOCS) proteins, particularly SOCS1, in regulating cytokine signaling pathways and maintaining immune balance. SOCS1 mimetics in particular, designed to enhance SOCS1 activity, represent a novel therapeutic approach aimed at mitigating inflammation and promoting neuroprotection. This review underscores the intricate interactions between cytokines, SOCS family proteins, and the pathophysiology of AE, emphasizing the potential of SOCS1 mimetics and potentially other SOCS mimetics as a targeted treatment. This review also emphasizes the need for further research to validate the efficacy and safety of SOCS1 mimetics in clinical settings and their role in improving outcomes for patients with AE.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":"e70023"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793094","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":"HLA-DR-Expressing γδ T Cells Facilitate the Anti-Leukemia Activity of αβ T Cells.","authors":"Keli Yue, Shuang Liang, Ning Wu, Mingzhu Jia, Haitao Gao, Cong Cheng, Lijuan Hu, Jiangying Liu","doi":"10.1002/eji.70025","DOIUrl":"https://doi.org/10.1002/eji.70025","url":null,"abstract":"<p><p>In addition to exhibiting significant cytotoxic capabilities, γδ T cells play a crucial role as a bridge between innate and adaptive immunity. Although γδ T cells have been demonstrated to orchestrate interactions with other immune cells, their impact on αβ T cells in the setting of acute myeloid leukemia (AML) remains unexplored. In this study, we found that functional deficiencies of αβ T cells were significantly associated with the downregulation of HLA-DR⁺ γδ T cells in patients newly diagnosed with AML. Vδ2⁺ T cells, which constitute a predominant subset of γδ T cells in human peripheral blood, exhibited elevated levels of HLA-DR following ex vivo expansion. Notably, a lower dose of the expanded Vδ2⁺ T cells did not induce direct cytotoxicity against AML cells; instead, they significantly enhanced the cytotoxic capacity of primary αβ T cells toward AML cells. Furthermore, blockade of HLA-DR on Vδ2⁺ T cells markedly diminished this facilitating effect. Taken together, our findings demonstrate an important indirect role for Vδ2⁺ T cells beyond their direct killing ability in the context of anti-AML immunity and provide novel insights into the therapeutic potential of adoptive Vδ2⁺ T cell therapy.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":"e70025"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797742","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":"Spatial Organisation of Tumour cDC1 States Correlates with Effector and Stem-Like CD8+ T Cells Location","authors":"Cécile Piot,&nbsp;Mariana Pereira da Costa,&nbsp;Adi Biram,&nbsp;Carlos M. Minutti,&nbsp;Kok Haw Jonathan Lim,&nbsp;Mary Green,&nbsp;Ania Mikolajczak,&nbsp;Robert P. Jenkins,&nbsp;Lucy Meader,&nbsp;Michael D. Buck,&nbsp;Ana Cardoso,&nbsp;Neil Rogers,&nbsp;Erik Sahai,&nbsp;Caetano Reis e Sousa","doi":"10.1002/eji.70011","DOIUrl":"https://doi.org/10.1002/eji.70011","url":null,"abstract":"<p>CD8⁺ T cells are central to targeting and eliminating cancer cells. Their function is critically supported by type 1 conventional dendritic cells (cDC1s), which both prime antigen-specific CD8⁺ T cells in tumour-draining lymph nodes (tdLNs) and sustain primed CD8⁺ T cells within tumours. Despite their importance, the spatiotemporal organisation of cDC1s within tumours and their diverse functional roles remain poorly understood. Here, we use scRNAseq and unbiased spatial analysis to construct a detailed map of cDC1 states and distribution within immunogenic mouse tumours during CD8⁺ T-cell-mediated rejection. We reveal two distinct cDC1 activation states characterised by differential expression of genes linked to anti-tumour immunity, including <i>Cxcl9</i> and <i>Il12b</i>. Strikingly, <i>Il12b</i>-expressing cDC1s are CCR7⁺ and enriched at tumour borders, where they closely associate with stem-like TCF1⁺ CD8⁺ T cells. In contrast, CCR7^– <i>Cxcl9</i>-expressing cDC1s are preferentially found within the tumour parenchyma alongside effector CD8⁺ T cells. Analysis of a published dataset of human tumours similarly reveals a spatial association between CCR7⁺ cDC1 and stem-like TCF1⁺ CD8⁺ T cells. These findings uncover a highly spatially coordinated interaction between cDC1s and CD8⁺ T cells within tumours, shedding light on the intricate cellular dynamics that underpin effective anti-tumour immunity.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751720","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":"Cover Story: Eur. J. Immunol. 8'25","authors":"","doi":"10.1002/eji.70031","DOIUrl":"https://doi.org/10.1002/eji.70031","url":null,"abstract":"<p>Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI's Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared by flow cytometry and immunology research experts from around the world.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751721","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":"Issue Information: Eur. J. Immunol. 8'25","authors":"","doi":"10.1002/eji.70032","DOIUrl":"https://doi.org/10.1002/eji.70032","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751719","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":"Aging and Viral Evolution Impair Immunity Against Dominant Pan-Coronavirus-Reactive T Cell Epitope","authors":"Lucie Loyal,&nbsp;Karsten Jürchott,&nbsp;Ulf Reimer,&nbsp;Lil Meyer-Arndt,&nbsp;Larissa Henze,&nbsp;Norbert Mages,&nbsp;Jak Kostrzanowski,&nbsp;Bernhard Reus,&nbsp;Maike Mangold,&nbsp;Beate Kruse,&nbsp;Manuela Dingeldey,&nbsp;Birgit Sawitzki,&nbsp;Janine Michel,&nbsp;Marica Grossegesse,&nbsp;Karsten Schnatbaum,&nbsp;Holger Wenschuh,&nbsp;Andreas Nitsche,&nbsp;Nils Lachmann,&nbsp;Bernd Timmermann,&nbsp;Claudia Giesecke-Thiel,&nbsp;Julian Braun,&nbsp;Florian Kern,&nbsp;Andreas Thiel","doi":"10.1002/eji.202551888","DOIUrl":"https://doi.org/10.1002/eji.202551888","url":null,"abstract":"<p>Immune evasion by escape mutations subverts immunity against SARS-CoV-2. A role of pan-coronavirus immunity for more durable protection is being discussed, but has remained understudied. We here investigated the effects of age, mutations, and homo-/heterologous vaccination regimens on the dominant pan-coronavirus-specific cellular and humoral epitope iCope after SARS-CoV-2 infection and vaccination in detail. In older individuals, the quantitatively and qualitatively reduced iCope-reactive CD4⁺ T cell responses with narrow TCR repertoires could not be enhanced by vaccination and were further compromised by emerging spike mutations. In contrast, pan-coronavirus-reactive humoral immunity was affected only by mutations and not by age. Our results reveal a distinct deficiency of the dichotomous layer of pan-coronavirus immunity in the older, critical for long-term protection against SARS-CoV-2 variants.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202551888","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717009","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":"Immunogenicity-Guided Design of an Acinetobacter baumanii Vaccine","authors":"Chenghua Zhu,&nbsp;Shuaiyuan Liang,&nbsp;Ning Yang,&nbsp;Shan Li,&nbsp;Jianpeng Xue,&nbsp;Runlu Zhou,&nbsp;Xiuwen Hong,&nbsp;Sixi Chen,&nbsp;Nan Gao,&nbsp;Qiang Du,&nbsp;Jianling Huang,&nbsp;Ganzhu Feng,&nbsp;Xingran Du","doi":"10.1002/eji.70019","DOIUrl":"https://doi.org/10.1002/eji.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>The development of vaccines represents a promising and safe strategy to combat multidrug-resistant (MDR) <i>Acinetobacter baumannii</i> (<i>A. baumannii</i>) infections. In this study, we designed and evaluated a dendritic cell (DC)-targeting multiepitope peptide-based biomimetic nanovaccine for its immunogenicity and protective efficacy in a murine model. Bioinformatics tools were employed to predict and screen B- and T-cell epitopes derived from the OmpW protein of <i>A. baumannii</i>, followed by immunological validation. The dominant epitopes were sequentially linked using 6-aminocaproic acid to synthesize a multiepitope peptide, rOmpW. Subsequently, rOmpW was encapsulated within polylactic-co-glycolic acid (PLGA) nanoparticles coated with neutrophil membranes (NM), and the surface was functionalized with a DC-targeting peptide (DCpep) to construct the biomimetic nanovaccine, DCpep-NM-PLGA-rOmpW. This biomimetic nanovaccine elicited robust Th1 and Th17 cellular immune responses, as well as humoral immunity, and demonstrated significant protective efficacy in a murine model of acute lethal pneumonia caused by <i>A. baumannii</i>. These findings underscore the translational potential of this biomimetic nanovaccine as a prophylactic strategy against <i>A. baumannii</i> infections.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716984","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}