European Journal of Immunology最新文献

{"title":"ISG15-Dependent Stabilisation of USP18 Is Necessary but Not Sufficient to Regulate Type I Interferon Signalling in Humans","authors":"Andri Vasou,&nbsp;Katie Nightingale,&nbsp;Vladimíra Cetkovská,&nbsp;Jonathan Scheler,&nbsp;Connor G. G. Bamford,&nbsp;Jelena Andrejeva,&nbsp;Jessica C. Rowe,&nbsp;Kirby N. Swatek,&nbsp;Ulrich Schwarz-Linek,&nbsp;Richard E. Randall,&nbsp;John McLauchlan,&nbsp;Michael P. Weekes,&nbsp;Dusan Bogunovic,&nbsp;David J. Hughes","doi":"10.1002/eji.202451651","DOIUrl":"https://doi.org/10.1002/eji.202451651","url":null,"abstract":"<p>Type I interferon (IFN) signalling induces the expression of several hundred IFN-stimulated genes (ISGs) that provide an unfavourable environment for viral replication. To prevent an overexuberant response and autoinflammatory disease, IFN signalling requires tight control. One critical regulator is the ubiquitin-like protein IFN-stimulated gene 15 (ISG15), evidenced by autoinflammatory disease in patients with inherited ISG15 deficiencies. Current models suggest that ISG15 stabilises ubiquitin-specific peptidase 18 (USP18), a well-established negative regulator of IFN signalling. USP18 also functions as an ISG15-specific peptidase that cleaves ISG15 from ISGylated proteins; however, USP18's catalytic activity is dispensable for controlling IFN signalling. Here, we show that the ISG15-dependent stabilisation of USP18 involves hydrophobic interactions reliant on tryptophan 123 (W123) in ISG15. Nonetheless, while USP18 stabilisation is necessary, it is not sufficient for the regulation of IFN signalling; ISG15 C-terminal mutants with significantly reduced affinity still stabilised USP18, yet the magnitude of signalling resembled ISG15-deficient cells. Hence, USP18 requires non-covalent interactions with the ISG15 C-terminal diGlycine motif to promote its regulatory function. It shows ISG15 is a repressor of type I IFN signalling beyond its role as a USP18 stabiliser.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380559","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":"Bystander Expression of Atypical Chemokine Receptor 2 Protects T Cells from Chemoattraction towards Cancer-Associated Fibroblasts","authors":"Richard Tang,&nbsp;Szun S. Tay,&nbsp;George Sharbeen,&nbsp;David Herrmann,&nbsp;Janet Youkhana,&nbsp;Paul Timpson,&nbsp;Phoebe A. Phillips,&nbsp;Maté Biro","doi":"10.1002/eji.202451215","DOIUrl":"https://doi.org/10.1002/eji.202451215","url":null,"abstract":"<p>Atypical chemokine receptors (ACKRs) are a subclass of chemokine receptors that internalise and degrade chemokines instead of eliciting chemotaxis. Scavenging by ACKRs reduces the local bioavailability of chemokines and can thus reshape chemokine gradients that direct leukocyte trafficking during inflammation and anticancer responses. In pancreatic ductal adenocarcinoma (PDAC), chemokine axes, such as CXCL12-CXCR4, are co-opted by cancer-associated fibroblasts (CAFs) for tumour growth and escape, and immunosuppression. Here, we explore the use of ACKRs to reshape chemokine gradients within the PDAC tumour microenvironment. ACKR2, previously only known to scavenge inflammatory CC chemokines, was recently shown to be able to interact with CXCL10 and CXCL14. Here, using a chemokine binding assay and cytometric bead arrays, we reveal that ACKR2 scavenges additional CXC chemokines CXCL12 and CXCL1. ACKR2 scavenges CXCL12 with reduced efficiency compared to ACKR3, previously reported to bind CXCL12. Finally, we demonstrate that the overexpression of ACKR2 on bystander cells protects primary murine cytotoxic T lymphocytes from PDAC CAF-mediated chemoattraction. These findings reveal new CXC chemokine ligands of ACKR2 and indicate that ACKR overexpression may protect T cells from misdirection by CAFs.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380554","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":"Rheumatoid Arthritis Related B-Cell Changes Are Found Already in the Risk-RA Phase","authors":"Charlotte de Vries,&nbsp;Wenqi Huang,&nbsp;Ravi Kumar Sharma,&nbsp;Kittikorn Wangriatisak,&nbsp;Sara Turcinov,&nbsp;Alexandra Cîrciumaru,&nbsp;Lars Rönnblom,&nbsp;Caroline Grönwall,&nbsp;Aase Hensvold,&nbsp;Karin Lundberg,&nbsp;Vivianne Malmström","doi":"10.1002/eji.202451391","DOIUrl":"https://doi.org/10.1002/eji.202451391","url":null,"abstract":"<p>Anti-cyclic citrullinated peptide2 (CCP2) antibody positivity in rheumatoid arthritis (RA) and in the predisease phase, together with the success of B-cell depletion, support a crucial role for B cells in RA pathogenesis. Yet, knowledge of B cells in the transition from autoimmunity to RA is limited, and therefore we here investigated B-cell changes during the risk-RA phase. B-cell phenotypes in 18 CCP2-positive risk-RA individuals with musculoskeletal complaints were studied, parallel with ten CCP2-positive RA patients and nine healthy controls. Nine of the risk-RA individuals progressed to RA. B-cell phenotypes were investigated using spectral flow cytometry. The results demonstrate that unswitched and switched memory B-cell frequencies in the risk-RA cohort were more similar to controls than RA patients. Yet, risk-RA progressors displayed an early activation profile amongst naïve B cells. Deeper characterization of the memory compartment revealed expansion of CD27-negative IgG+ B cells both in RA compared with controls (<i>p</i> = 0.0172) and in risk-RA progressors versus non-progressors (<i>p</i> = 0.0295). Overall, we demonstrate that the phenotypic distribution of B cells is altered in the risk-RA phase. This includes changes in CD27-negative class-switched B cells, which have been attributed to autoreactive and anergic features implicating a possible contribution to RA development.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380482","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":"HCMV Variants Expressing ULBP2 Enhance the Function of Human NK Cells via its Receptor NKG2D","authors":"Greta Meyer,&nbsp;Anna Rebecca Siemes,&nbsp;Jenny F. Kühne,&nbsp;Irina Bevzenko,&nbsp;Viktoria Baszczok,&nbsp;Jana Keil,&nbsp;Kerstin Beushausen,&nbsp;Karen Wagner,&nbsp;Lars Steinbrück,&nbsp;Martin Messerle,&nbsp;Christine S. Falk","doi":"10.1002/eji.202451266","DOIUrl":"https://doi.org/10.1002/eji.202451266","url":null,"abstract":"<p>The immunosuppressed state of transplant patients allows opportunistic pathogens such as human cytomegalovirus (HCMV) to cause severe disease. Therefore, inducing and boosting immunity against HCMV in recipients prior to organ transplantation is highly desirable, and accordingly, the development of an HCMV vaccine has been identified as a clinically relevant priority. Such vaccines need to be highly attenuated while eliciting specific and protective immune responses. We tested the concept of expressing the NKG2D ligand (NKG2D-L) ULBP2 by HCMV vaccine candidates to achieve NK cell activation, and, thereby viral attenuation. ULBP2 expression was found on HCMV-infected cells, reflecting the promotor strengths used to drive ULBP2 transgene expression. Moreover, significantly increased shedding of soluble ULBP2 (sULBP2) was detected for these mutants mirroring the surface expression levels. No negative effect of sULBP2 on NK cell function was observed. NK cells efficiently controlled viral spread, which was further increased by additional triggering of the activating receptor NKG2D. Engagement of NKG2D was also confirmed by its downregulation depending on ULBP2 surface density. Finally, expression of ULBP2 significantly enhanced NK cell cytotoxicity, which was independent of KIR-ligand mismatch as well as the presence of T cells. This NKG2D-L-based approach represents a feasible and promising strategy for HCMV vaccine development.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380561","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":"NK Cell Immaturity and NKp30 Expression Positively Correlate with Clinical Outcome in Multiple Myeloma Patients from the IFM2009 Clinical Trial","authors":"Marine Villard,&nbsp;Sébastien Viel,&nbsp;Lionel Karlin,&nbsp;Hervé Avet-Loiseau,&nbsp;Ludovic Martinet,&nbsp;Antoine Marçais,&nbsp;Thierry Walzer","doi":"10.1002/eji.202451191","DOIUrl":"https://doi.org/10.1002/eji.202451191","url":null,"abstract":"<div>\u0000 \u0000 <p>Multiple myeloma (MM) is a proliferation of tumoral plasma cells that is still incurable. Natural killer (NK) cells can recognize and kill MM cells in vitro. However, previous literature suggests an alteration of NK cell function in MM patients. To further evaluate this point, we used multi-parametric flow cytometry to monitor NK cell phenotype in bone marrow samples at diagnosis of MM, taking advantage of the IFM2009 trial and associated samples. Our results show an increase in the frequency of NK cells in MM patients. A detailed analysis of NK cell phenotype showed a decreased expression of terminal maturation markers such as KLRG1 or CD57 and an increased expression of CD56^bright/tissue resident markers among NK cells from MM patients. The extent of these alterations is even more pronounced as the ISS score increases in patients. Finally, a favorable clinical evolution correlates with NK cell immaturity, on the one hand, and with the level of NKp30, a receptor more expressed in immature NK cells on the other hand. Altogether, these data suggest that immature and resident NK cells are particularly involved in the anti-myeloma response, notably via NKp30, which could pave the way for future therapeutic strategies.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380483","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":"Deciphering the Human Germinal Center: A Review of Models to Study T–B Cell Interactions","authors":"Elisa Fleischmann,&nbsp;Vera Middelkamp,&nbsp;Theo van den Broek","doi":"10.1002/eji.202451460","DOIUrl":"https://doi.org/10.1002/eji.202451460","url":null,"abstract":"<p>Interactions between T- and B cells in the germinal center reaction are instrumental for the initiation, maintenance, and downregulation of the human adaptive immune response, leading to the production of antigen-specific antibodies and long-lasting immunological memory. Replicating the human immune system remains challenging, with an over-reliance on animal models with limited translational accuracy. There is an increasing need for new tools that accurately model human immune function. This review evaluates existing 2D and 3D in vitro and ex vivo human models for their ability to reproduce the germinal center reaction, with a particular focus on T- and B-cell interaction. We conclude that although current models are able to replicate certain features of the germinal center reaction, no current model is able to completely replicate the complex human GC process. We outline the challenges in recreating a fully functional germinal center and suggest future directions of research to improve existing models, ultimately bringing us closer to completely reproducing the human lymph node.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380558","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":"Transcriptomic Signatures Predict Rubella Virus-Induced Cytokine and Chemokine Responses in Female MMR Recipients","authors":"Tamar Ratishvili,&nbsp;Iana H. Haralambieva,&nbsp;Huy Q. Quach,&nbsp;Ilya M. Swanson,&nbsp;Krista M. Goergen,&nbsp;Diane E. Grill,&nbsp;Inna G. Ovsyannikova,&nbsp;Richard B. Kennedy,&nbsp;Gregory A. Poland","doi":"10.1002/eji.202451303","DOIUrl":"https://doi.org/10.1002/eji.202451303","url":null,"abstract":"<p>The study examined the relationship between rubella virus (RV)-induced gene expression and proinflammatory cytokine/chemokine secretion in females previously vaccinated with MMR. Gene clusters enriched for functional pathways of innate immune system activation and antiviral responses were found to predict RV-specific MCP-1, MCP-4, IP-10, and IL-2 secretion.\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 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380556","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":"Cover Story: Eur. J. Immunol. 2'25","authors":"","doi":"10.1002/eji.202570021","DOIUrl":"https://doi.org/10.1002/eji.202570021","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 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202570021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380013","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. 2'25","authors":"","doi":"10.1002/eji.202570022","DOIUrl":"https://doi.org/10.1002/eji.202570022","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202570022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380014","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":"Striking the Right Chord at EJI: Introducing Editor-in-Chief Matteo Iannacone and the Seamless Transfer Policy","authors":"Matteo Iannacone,&nbsp;Nadja Bakocevic","doi":"10.1002/eji.202551784","DOIUrl":"10.1002/eji.202551784","url":null,"abstract":"&lt;p&gt;Matteo Iannacone received his M.D. from the University of Milan, completed a residency in Internal Medicine, and earned a Ph.D. in Immunology at Vita-Salute San Raffaele University in Milan, Italy. After postdoctoral training at The Scripps Research Institute (La Jolla, CA) and at Harvard Medical School (Boston, MA), he returned to Milan, where he now serves as Director of the Division of Immunology, Transplantation, and Infectious Diseases, Professor of pathology, and Head of the Dynamics of Immune Responses Laboratory at the San Raffaele Scientific Institute and University. Having joined EJI's Executive Committee in 2021, he takes on the role of EJI's academic Editor-in-Chief starting January 2025.&lt;/p&gt;&lt;p&gt;My laboratory's work centers on understanding how immune responses are orchestrated within local tissue niches. Recent breakthroughs in intravital imaging and spatially resolved omics have enabled us to visualize and quantify interactions at cellular resolution in living organisms, revealing unprecedented details about how immune cells—and even nonimmune cells—behave and communicate.&lt;/p&gt;&lt;p&gt;In our lab, we combine these powerful tools—high-resolution imaging, single-cell sequencing, and advanced computational analyses—to dissect how local processes converge to influence immune outcomes. By focusing on phenomena such as how T cells exert immune surveillance and examining immunological crosstalk across different tissues, we aim to bridge the gap between discrete molecular events and broader physiological consequences. This holistic perspective is particularly relevant in complex conditions like infectious diseases and cancer, where local cell-to-cell interactions can be a pivotal driver of disease progression. Ultimately, our goal is to uncover novel principles of tissue immunity and leverage them for more precise immunotherapeutic strategies.&lt;/p&gt;&lt;p&gt;I have a long-standing appreciation for the &lt;i&gt;European Journal of Immunology&lt;/i&gt; (EJI). Early in my career, I would often turn to EJI as a reliable source of rigorous immunological research. The journal's commitment to quality and its role in the global immunology community resonate strongly with my own vision. Furthermore, my time on the Executive Committee allowed me to be actively involved in strategic decisions. I feel privileged to succeed outstanding leaders, including our outgoing Editor-in-Chief, Chiara Romagnani, and to continue the legacy of excellence set by Jim Di Santo, whose 9-year term was remarkable. I am grateful to the entire EJI team for preserving the journal's values and scientific rigor through all kinds of challenges.&lt;/p&gt;&lt;p&gt;At the heart of my editorial vision lies a firm commitment to publishing rigorous, high-quality science while fostering an author-friendly environment. We have recently updated policies to enhance transparent communication between referees and authors, and we continue to strengthen our ties with EFIS to support young immunologists. Building on past success,","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202551784","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062178","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}