European Journal of Immunology最新文献

{"title":"Fever-Induced Heat Shock Protein-70 Regulates Macrophage IL-1β and IL-10 Secretion During Mycobacterium tuberculosis Infection","authors":"Deborah L. W. Chong,&nbsp;Sajeel A. Shah,&nbsp;Julia Kutschenreuter,&nbsp;Ramla Cusman,&nbsp;Meena Murugananden Pillai,&nbsp;Daniela E. Kirwan,&nbsp;Robert H. Gilman,&nbsp;Jon S. Friedland","doi":"10.1002/eji.202551963","DOIUrl":"https://doi.org/10.1002/eji.202551963","url":null,"abstract":"<p>Fever is a common clinical symptom in patients with tuberculosis (TB). During fever, heat-shock proteins (HSPs), such as HSP70, are expressed, which are molecular chaperones regulating protein folding and may also have immunomodulatory properties. How fever modulates immune responses during TB and by which mechanisms is unknown. In this study, we investigated the effects of fever, and specifically the role of HSP70, on <i>Mycobacterium tuberculosis</i> (<i>Mtb)</i>-induced macrophage inflammatory responses. Human monocyte-derived macrophages (MDM) were infected with <i>Mtb</i> at 37°C or 40°C to mimic febrile conditions. Fever suppresses <i>Mtb</i>-induced IL-1β and IL-10 gene expression and secretion from MDM, but enhances <i>Mtb</i>-induced HSP70 secretion and intracellular accumulation in MDM. Extracellular HSP70 and HSP70-expressing macrophages are abundant in granulomas in TB patient biopsies. HSP70 antagonism decreases <i>Mtb</i>-induced IL-1β secretion during febrile conditions but has no significant effect on IL-10 secretion. Pretreatment of MDM with recombinant HSP70 significantly increases <i>Mtb</i>-induced IL-1β at 37°C. Finally, extracellular HSP70 negatively regulates further HSP70 secretion from MDM during <i>Mtb</i> infection. Overall, fever and subsequent HSP70 expression modulates proinflammatory innate immune response in TB, which may have implications for the development of host-directed therapies.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202551963","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634979","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":"T Cell Response Evaluation After A Fifth Dose of an Inactivated SARS-CoV-2 Vaccine Using Multiparametric Flow Cytometry","authors":"Francisca Román,&nbsp;Antonia Reyes,&nbsp;Cristián Gutiérrez,&nbsp;Linmar Rodríguez-Guilarte,&nbsp;Constanza Méndez,&nbsp;Daniela Moreno-Tapia,&nbsp;Mariana Ríos,&nbsp;Alex Cabrera,&nbsp;Leandro J. Carreño,&nbsp;Pablo A. González,&nbsp;Susan M. Bueno,&nbsp;Alexis M. Kalergis,&nbsp;Hernán F. Peñaloza","doi":"10.1002/eji.202551848","DOIUrl":"https://doi.org/10.1002/eji.202551848","url":null,"abstract":"<p>The T cell response induced by SARS-CoV-2 vaccines is an essential component of immune protection against COVID-19. Multiparametric flow cytometry analysis emerges as a valuable tool for in-depth assessment of T cell phenotype nuances that occur after booster vaccination, such as a fifth dose of an inactivated SARS-CoV-2 vaccine. Figure created with BioRender.com.\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 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634977","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":"Human Type-I Interferon Omega Holds Potent Antiviral Properties and Promotes Cytolytic CD8+ T Cell Responses","authors":"Hoang Oanh Nguyen,&nbsp;Patricia Recordon Pinson,&nbsp;Marie-Line Andreola,&nbsp;Laura Papagno,&nbsp;Victor Appay","doi":"10.1002/eji.70003","DOIUrl":"https://doi.org/10.1002/eji.70003","url":null,"abstract":"<div>\u0000 \u0000 <p>The type-I interferon family is well known for its critical role in innate immunity. It comprises several members, among which IFN-α₂ and IFN-β are the most extensively studied, with important antiviral and immune-modulatory functions. Recent findings linking autoantibodies against type-I interferons to severe COVID-19 suggest a potential role for IFN-ω in combating SARS-CoV-2 infection. However, little is known about human IFN-ω, as most research on this interferon has been conducted in feline models. Here, we demonstrate that human IFN-ω is secreted at levels comparable to those of IFN-α₂ or IFN-β upon stimulation with inflammatory agonists and triggers a robust antiviral response, inhibiting SARS-CoV-2 infection <i>in vitr</i><i>o</i>. Moreover, IFN-ω enhances the effector functions of antigen-specific CD8⁺ T cells primed <i>de novo</i> from healthy donor cells, highlighting its capacity to promote strong cellular immunity. Our results position IFN-ω as a key member of the type-I interferon family, with promising potential for therapeutic and vaccine applications.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615192","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":"Innate Lymphoid Cells in Reproductive Health and Disease","authors":"Francesco Colucci,&nbsp;Marco Botta","doi":"10.1002/eji.70007","DOIUrl":"https://doi.org/10.1002/eji.70007","url":null,"abstract":"<p>Half a kilogram of immune cells reside in tissues. In the uterus, innate lymphoid cells (ILC) contribute to the cyclic destruction and repair of the mucosa. During pregnancy, uterine ILC support the formation of the placenta and the growth of the fetus. They also contribute to immune responses to pathogens. ILC respond quickly to signals of tissue perturbations and, by influencing other immune cells, they organise responses that help maintain tissue health. Their functions have been determined in the respiratory and intestinal tracts, skin, liver and adipose tissue. It is challenging to determine the function of uterine ILC because of the cyclic changes of the endometrium and the difficulties in accessing human tissues during pregnancy. We review the existing literature on the involvement of uterine ILC in physiology and pathology of the non-pregnant endometrium as well as in pregnancy, from implantation of the fertilised egg to the tissue remodelling occurring during the first trimester and that leads to the formation of the placenta which sustains fetal growth, until parturition.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624300","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":"AK2-Deficient Mice Recapitulate Impaired Lymphopoiesis of Reticular Dysgenesis Patients, but Also Lack Erythropoiesis","authors":"Rebekka Waldmann,&nbsp;Franziska Werner,&nbsp;Alpaslan Tasdogan,&nbsp;Felix Immanuel Maier,&nbsp;Ursula Kohlhofer,&nbsp;Irene Gonzalez-Menendez,&nbsp;Leticia Quintanilla de Fend,&nbsp;Amrit Kaur Puarr,&nbsp;Ruth Maree Arkell,&nbsp;Anselm Enders,&nbsp;Manfred Hoenig,&nbsp;Hubert Schrezenmeier,&nbsp;Hans Joerg Fehling,&nbsp;Klaus Schwarz,&nbsp;Ulrich Pannicke","doi":"10.1002/eji.202451466","DOIUrl":"https://doi.org/10.1002/eji.202451466","url":null,"abstract":"<p>Reticular dysgenesis (RD) is a rare genetic disorder caused by mutations in the adenylate kinase 2 (<i>AK2</i>) gene. It is characterized by a T⁻B⁻ severe combined immunodeficiency, agranulocytosis, and sensorineural deafness. We established and characterized a haematopoiesis-specific conditional <i>Ak2</i>-knockout mouse model to provide a model system to study the molecular pathophysiology of RD. As expected from the human phenotype of RD, haematopoiesis-specific AK2-deficient embryos had a small, atrophic thymus consisting mainly of epithelial cells. No recognizable T-cell component was observed, but B-cell lineage precursor cells were present in the foetal liver. The effects of AK2 deficiency on myelopoiesis were less severe in mice than in humans. The absolute numbers of monocytes, macrophages, granulocytes and megakaryocytes in foetal liver as well as colony-forming precursors were not reduced. In contrast to humans, haematopoiesis-specific <i>Ak2</i>-knockout mice exhibit embryonic lethality between E13 and E15 due to severe anaemia caused by an early block in definitive erythropoiesis. Murine erythroid progenitors mainly express AK2 and only low levels of functionally related kinases, which are unable to compensate for AK2 deficiency, in contrast to human erythroid progenitors.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451466","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615191","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. 7'25","authors":"","doi":"10.1002/eji.70005","DOIUrl":"https://doi.org/10.1002/eji.70005","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 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589684","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":"Meeting Report: German–Japanese Alliance in Immunology","authors":"Christina E. Zielinski,&nbsp;Koji Tokoyoda,&nbsp;Florian Wimmers,&nbsp;Osamu Takeuchi","doi":"10.1002/eji.202552172","DOIUrl":"https://doi.org/10.1002/eji.202552172","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582364","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":"nuTCRacker: Predicting the Recognition of HLA-I–Peptide Complexes by αβTCRs for Unseen Peptides","authors":"Justin Barton,&nbsp;Trupti Gore,&nbsp;Meghna Phanichkrivalkosil,&nbsp;Adrian Shepherd,&nbsp;Michele Mishto","doi":"10.1002/eji.202451607","DOIUrl":"https://doi.org/10.1002/eji.202451607","url":null,"abstract":"<p>The ability to predict which antigenic peptide(s) the αβTCR of a given CD8⁺ T-cell clone can recognise would represent a quantum leap in the understanding of T-cell repertoire selection and development of targeted cell-mediated immunotherapies. Current methods fail to make accurate predictions for antigenic peptides not present in the training dataset. Here, we propose a novel deep learning method called nuTCRacker that makes accurate predictions for a subset of unseen peptides, with an AUC &gt; 0.7 for around a third of peptides evaluated using a large dataset compiled from curated public resources. An additional evaluation was undertaken using a small cellula-validated dataset of αβTCR peptides associated with cancer. Our analysis suggests that it is possible to make useful predictions for an unseen peptide provided the training dataset contains: many samples with the same HLA class I molecule as that bound to the peptide; at least one peptide that is similar to the target peptide; and a small number of αβTCRs that are similar to those bound to the unseen peptide of interest.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451607","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582280","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":"Immunological and Clinical Markers of Post-acute Sequelae of COVID-19: Insights from Mild and Severe Cases 6 Months Post-infection","authors":"William Mouton,&nbsp;Sophia Djebali,&nbsp;Marine Villard,&nbsp;Omran Allatif,&nbsp;Cécile Chauvel,&nbsp;Sarah Benezech,&nbsp;Philippe Vanhems,&nbsp;Jacqueline Marvel,&nbsp;Thierry Walzer,&nbsp;Sophie Trouillet-Assant","doi":"10.1002/eji.202551948","DOIUrl":"https://doi.org/10.1002/eji.202551948","url":null,"abstract":"<p>Post-acute sequelae of COVID-19 (PASC) are a complex clinical condition that requires a better understanding of its underlying biological mechanisms. In this study, we assessed hundreds of virological, serological, immunological, and tissue damage biomarkers in two cohorts of patients who had experienced either mild (<i>n</i> = 270) or severe (<i>n</i> = 188) COVID-19, 6 to 9 months post-initial infection, and in which 40% and 57.4% of patients, respectively, developed PASC. Blood analysis showed that the main differences observed in humoral, viral, and biological biomarkers were associated with the initial COVID-19 severity, rather than being specifically linked to PASC. However, patients with PASC displayed altered CD4⁺ and CD8⁺ memory T cell subsets, with higher cytokine-secreting cells and increased terminally differentiated CD45RA⁺ effector memory T cells (TEMRA). Elevated SARS-CoV-2-specific T cells responsive to nucleocapsid/membrane proteins with a TEMRA phenotype were also observed. A random forest model identified these features and initial symptom duration as top variables discriminating PASC, achieving over 80% classification accuracy.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202551948","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582279","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":"Correction to “cIAP-2 and Survivin Contribute to Cytokine-Mediated Delayed Eosinophil Apoptosis”","authors":"","doi":"10.1002/eji.202570063","DOIUrl":"https://doi.org/10.1002/eji.202570063","url":null,"abstract":"&lt;p&gt;E. M. Vassina, S. Yousefi, D. Simon, C. Zwicky, S. Conus, and H.-U. Simon, “CIAP-2 and Survivin Contribute to Cytokine-Mediated Delayed Eosinophil Apoptosis,” &lt;i&gt;European Journal of Immunology&lt;/i&gt; 36, no. 7 (2006): 1975–1984, https://doi.org/10.1002/eji.200635943.&lt;/p&gt;&lt;p&gt;Concerns were raised by a third party regarding duplicated image panels within Figure 2A, between the cIAP-1 and cIAP-2 normal neutrophil subpanels. The authors acknowledged the image compilation error, and as the original raw data were no longer available, they repeated the experiment. The new data confirmed that the corresponding experimental results and the overall conclusions of the paper remain unaffected. The corrected panels of Figure 2A, the full-length immunoblots, and the updated methods are below. The authors apologize for this mistake.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Corrected image panels of Figure&lt;/b&gt; 2A&lt;/p&gt;&lt;p&gt;Lack of expression of cIAP-1 and cIAP-2 in freshly purified normal human neutrophils compared to THP-1 and HL-60 cell lines. Immunoblot analysis was performed to assess protein expression. No detectable levels of cIAP-1 or cIAP-2 were observed in normal blood neutrophils. Lysates from THP-1 and HL-60 cells served as controls. Membranes were re-probed with anti-GAPDH monoclonal antibody to confirm equal protein loading.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Full-length immunoblots of the repeated experiments&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Full-length immunoblots are shown for cIAP-1, cIAP-2, and GAPDH protein expression. Each lane was loaded with 50 µg of total cell lysate derived from either human blood neutrophils or the control cell lines THP-1 and HL-60. GAPDH served as a loading control.&lt;/p&gt;&lt;p&gt;Peripheral blood neutrophils from control individuals were purified as described [&lt;span&gt;1&lt;/span&gt;] and were &gt;98% pure. For control experiments, the human promyelocytic leukemia cell line HL-60 clone 15 and the human monocytic leukemia cell line THP-1 (both from ATCC, Manassas, VA, USA) were used.&lt;/p&gt;&lt;p&gt;Cell-free extracts and immunoblotting were performed as previously described [&lt;span&gt;2&lt;/span&gt;]. Briefly, cell pellets were resuspended in lysis buffer (50 mM Tris-HCl [pH 7.4], 150 mM NaCl, 10% glycerol, 1% Triton X-100, 1% NP-40, 2 mM EDTA, 2.5 mM MgCl₂, 2.5 mM NaF, 10 mM sodium pyrophosphate, and 200 µM sodium orthovanadate), freshly supplemented with protease inhibitor cocktail (Sigma-Aldrich), 1 mM PMSF (Sigma-Aldrich), and 1 × PhosSTOP phosphatase inhibitor cocktail (Roche). Cells were collected, washed with PBS, and lysed on ice for 20 min. Lysates were clarified by high-speed centrifugation (13,000 rpm, 15 min, 4 °C). Protein concentrations were determined using the Pierce BCA protein assay kit (Thermo Fisher Scientific).&lt;/p&gt;&lt;p&gt;Equal amounts of protein (50 µg) were denatured and separated on 12% SERVAGel TG PRiME gels (SERVA Electrophoresis, Heidelberg, Germany), followed by transfer onto Immobilon-P PVDF membranes (Merck Millipore). Membranes were blocked with 5% nonfat dry milk in TBST (20 mM Tris-HCl, 150 mM NaCl, 0.1% Tween 20","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202570063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582281","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}