European Journal of Immunology最新文献_第2页

Activation of the Complement/Lectin Pathway, Angiopoietin/Tie-2/VEGF-System, Cytokines and Chemokines in Different Angioedema Subtypes 补体/凝集素途径、血管生成素/Tie-2/ vegf系统、细胞因子和趋化因子在不同血管性水肿亚型中的激活

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-07-20 DOI: 10.1002/eji.70010

Katharina Marlies Duda, Manuela Gehring, Bettina Wedi

{"title":"Activation of the Complement/Lectin Pathway, Angiopoietin/Tie-2/VEGF-System, Cytokines and Chemokines in Different Angioedema Subtypes","authors":"Katharina Marlies Duda, Manuela Gehring, Bettina Wedi","doi":"10.1002/eji.70010","DOIUrl":"https://doi.org/10.1002/eji.70010","url":null,"abstract":"The precise molecular mechanisms underlying angioedema attacks in cases of C1-inhibitor-deficient hereditary angioedema (C1-INH-HAE), angiotensin-converting enzyme inhibitor-induced angioedema (ACEi-AE), and mast cell-/histamine-mediated angioedema (Hist-AE) are not well understood. These attacks may involve immune and inflammatory mechanisms. We compared serum biomarkers indicating vascular integrity, leakage, angiogenesis, coagulation, and inflammation. During an attack-free period, we assessed 34 markers simultaneously using multi- and/or singleplex ELISA in 25 patients with C1-INH-HAE, 17 with ACEi-AE, 25 with Hist-AE, and 23 healthy controls. Differential blood counts, C1-INH-HAE-specific laboratory parameters, and recently developed assays addressing early complement and lectin pathways were included. The results revealed significant differences, as well as some similarities. Tie-2, VEGFs, C1s/C1INHc appear to play a role in all AE types regardless of whether they are bradykinin- or histamine-mediated. Furthermore, evidence was found for a role of IL-17, eosinophil, and neutrophil chemotactic factors, and the activation of these granulocytes was found. MASP-1/C1-INHc indicated early activation of the lectin pathway in ACEi-AE and HistAE, but not in C1-INH-HAE. C1s/C1-INHc and MASP-1/C1INHc ratio was able to discriminate C1-INH-HAE from controls and the other AE types. Future investigations in C1-INH-HAE, ACEi-AE, and Hist-AE should not only focus on complement activation but also the interaction with granulocytes.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666458","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

Homeobox Transcription Factor HOXB4 Distinctly Modulates Th2 and Th9 Cell Differentiation 同源盒转录因子HOXB4明显调节Th2和Th9细胞分化

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-07-20 DOI: 10.1002/eji.202451752

Shagnik Chattopadhyay, Sayantee Hazra, Biswajit Biswas, Ritobrata Goswami

{"title":"Homeobox Transcription Factor HOXB4 Distinctly Modulates Th2 and Th9 Cell Differentiation","authors":"Shagnik Chattopadhyay, Sayantee Hazra, Biswajit Biswas, Ritobrata Goswami","doi":"10.1002/eji.202451752","DOIUrl":"https://doi.org/10.1002/eji.202451752","url":null,"abstract":"<div>\u0000 \u0000 CD4+ T helper cells are involved in multiple biological processes ranging from pathogen clearance to immune tolerance. Differentiation of CD4+ T cells into varied subsets is dependent on transcription factors, cytokines, micronutrients, and epigenetic modifications. Here, we report the molecular mechanisms imparted by the homeobox transcription factor HOXB4 in modulating Th2 and Th9 cell differentiation. We found that Hoxb4 induction in T helper cells was TGF-β-dependent. In Th9 cells, HOXB4 overexpression significantly increased IL-9 secretion, while in Th2 cells, HOXB4 could alter only IL-10 secretion among other type 2 cytokines. Promoter activity analyses revealed that HOXB4 was able to transactivate the Il9 and Il10 proximal promoters, while the Il4 and Il13 promoters were differentially modulated. We observed that HOXB4 could physically interact with the transcription factor PU.1 but not GATA3, and directly bind PU.1 response element on the DNA in Th9 cells. The recruitment of HOXB4 was found to be significantly increased in regulatory regions including cECR and CNS1 (Il9 promoter). Collectively, our findings suggest that HOXB4 works downstream of the TGF-β signalling pathway, associates with PU.1, binds the regulatory regions, and distinctly regulates both Th2 and Th9 cell differentiation.\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666455","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

Teriflunomide Inhibits Human FOXP3+ Regulatory T Cell Function by Interference With Mitochondrial Respiration 特立氟米特通过干扰线粒体呼吸抑制人FOXP3+调节性T细胞功能

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-07-20 DOI: 10.1002/eji.202451260

Aleksandra Dyczko, Beatriz F. Côrte-Real, Ibrahim Hamad, Ralf A. Linker, Markus Kleinewietfeld

{"title":"Teriflunomide Inhibits Human FOXP3+ Regulatory T Cell Function by Interference With Mitochondrial Respiration","authors":"Aleksandra Dyczko, Beatriz F. Côrte-Real, Ibrahim Hamad, Ralf A. Linker, Markus Kleinewietfeld","doi":"10.1002/eji.202451260","DOIUrl":"https://doi.org/10.1002/eji.202451260","url":null,"abstract":"<div>\u0000 \u0000 Regulatory FOXP3+ T cells (Tregs) have been characterized with unique metabolic demands, preferentially relying on fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS). Several studies have indicated that Treg mitochondrial fitness is crucial for maintaining their stability and suppressive activity with an emphasis on complex-III of the electron transport chain (ETC). Dysfunctional Tregs isolated from patients with autoimmunity like multiple sclerosis (MS) show diminished mitochondrial respiration and the induction of a T helper (Th)1-like phenotype, characterized by increased production of interferon (IFN)-γ. Teriflunomide reduces the proliferation of activated T and B lymphocytes by inhibition of de novo pyrimidine synthesis, providing therapy for patients with autoimmune diseases. Recent data demonstrated that teriflunomide further inhibited complex-III activity in line with hampered mitochondrial respiration in T cells. Considering the essential role of OXPHOS and complex-III activity for Tregs, we therefore thought to investigate with this study the effects of teriflunomide on immunometabolism and function in human Tregs. Interestingly, teriflunomide impaired the mitochondrial function of human Tregs and further induced a Th1-like phenotype in line with defective suppressive activity. Our findings suggest that teriflunomide may potentially exert distinct effects on pro- versus anti-inflammatory T cell subsets, indicating the need for further detailed evaluation.\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666456","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 Tumour Glyco-Code: Sialylation as a Mediator of Stromal Cell Immunosuppression in the Tumour Microenvironment 肿瘤糖密码：唾液酰化作为肿瘤微环境中基质细胞免疫抑制的中介

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-07-16 DOI: 10.1002/eji.70000

Aoise O'Neill, Norashikin Zakaria, Hannah Egan, Oliver Treacy, Aisling M. Hogan, Michael O'Dwyer, Sean O. Hynes, Aideen E. Ryan

{"title":"The Tumour Glyco-Code: Sialylation as a Mediator of Stromal Cell Immunosuppression in the Tumour Microenvironment","authors":"Aoise O'Neill, Norashikin Zakaria, Hannah Egan, Oliver Treacy, Aisling M. Hogan, Michael O'Dwyer, Sean O. Hynes, Aideen E. Ryan","doi":"10.1002/eji.70000","DOIUrl":"https://doi.org/10.1002/eji.70000","url":null,"abstract":"The tumour microenvironment (TME) comprises a complex interplay of tumour cells, nonmalignant cells (including endothelial, immune, and stromal cells), and secreted factors within the extracellular matrix (ECM). Immunosuppression within the TME significantly hinders the efficacy of cancer immunotherapies. Stromal-rich TMEs, characterised by an abundance of mesenchymal stromal cells (MSCs) and cancer-associated fibroblasts (CAFs), are particularly immunosuppressive and associated with poor responses to conventional and immune-based therapies. Glycans, carbohydrate structures on cell surfaces, are dynamically regulated during tumourigenesis and mediate crucial cell–cell communications through receptor–ligand interactions. Sialylation, the addition of sialic acids to glycans, forms sialoglycans that can engage inhibitory Siglec receptors expressed on immune cells and promote immunosuppressive signalling. Emerging evidence implicates aberrant sialylation in the TME as a key driver of immunosuppression. More recently, sialylation of stromal cells in the TME has been shown to suppress anti-tumor immunity. This review explores the role of sialylation within stromal-rich, immunosuppressive TMEs, focusing on how specific sialic acid/Siglec interactions dictate innate and adaptive immune responses. We discuss the potential of targeting glycoimmune checkpoints to overcome stromal-mediated resistance and enhance anti-tumour immunity.","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.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634978","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

Fever-Induced Heat Shock Protein-70 Regulates Macrophage IL-1β and IL-10 Secretion During Mycobacterium tuberculosis Infection 热休克蛋白70调控结核分枝杆菌感染时巨噬细胞IL-1β和IL-10的分泌

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-07-16 DOI: 10.1002/eji.202551963

Deborah L. W. Chong, Sajeel A. Shah, Julia Kutschenreuter, Ramla Cusman, Meena Murugananden Pillai, Daniela E. Kirwan, Robert H. Gilman, Jon S. Friedland

{"title":"Fever-Induced Heat Shock Protein-70 Regulates Macrophage IL-1β and IL-10 Secretion During Mycobacterium tuberculosis Infection","authors":"Deborah L. W. Chong, Sajeel A. Shah, Julia Kutschenreuter, Ramla Cusman, Meena Murugananden Pillai, Daniela E. Kirwan, Robert H. Gilman, Jon S. Friedland","doi":"10.1002/eji.202551963","DOIUrl":"https://doi.org/10.1002/eji.202551963","url":null,"abstract":"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 Mycobacterium tuberculosis (Mtb)-induced macrophage inflammatory responses. Human monocyte-derived macrophages (MDM) were infected with Mtb at 37°C or 40°C to mimic febrile conditions. Fever suppresses Mtb-induced IL-1β and IL-10 gene expression and secretion from MDM, but enhances Mtb-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 Mtb-induced IL-1β secretion during febrile conditions but has no significant effect on IL-10 secretion. Pretreatment of MDM with recombinant HSP70 significantly increases Mtb-induced IL-1β at 37°C. Finally, extracellular HSP70 negatively regulates further HSP70 secretion from MDM during Mtb 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.","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}

引用次数: 0

T Cell Response Evaluation After A Fifth Dose of an Inactivated SARS-CoV-2 Vaccine Using Multiparametric Flow Cytometry 使用多参数流式细胞术评估第五剂灭活疫苗后的T细胞反应

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-07-16 DOI: 10.1002/eji.202551848

Francisca Román, Antonia Reyes, Cristián Gutiérrez, Linmar Rodríguez-Guilarte, Constanza Méndez, Daniela Moreno-Tapia, Mariana Ríos, Alex Cabrera, Leandro J. Carreño, Pablo A. González, Susan M. Bueno, Alexis M. Kalergis, Hernán F. Peñaloza

引用次数: 0

Innate Lymphoid Cells in Reproductive Health and Disease 先天淋巴样细胞在生殖健康和疾病中的作用

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-07-14 DOI: 10.1002/eji.70007

Francesco Colucci, Marco Botta

引用次数: 0

Human Type-I Interferon Omega Holds Potent Antiviral Properties and Promotes Cytolytic CD8+ T Cell Responses 人类i型干扰素Omega具有有效的抗病毒特性并促进细胞溶解CD8+ T细胞反应

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-07-14 DOI: 10.1002/eji.70003

Hoang Oanh Nguyen, Patricia Recordon Pinson, Marie-Line Andreola, Laura Papagno, Victor Appay

{"title":"Human Type-I Interferon Omega Holds Potent Antiviral Properties and Promotes Cytolytic CD8+ T Cell Responses","authors":"Hoang Oanh Nguyen, Patricia Recordon Pinson, Marie-Line Andreola, Laura Papagno, Victor Appay","doi":"10.1002/eji.70003","DOIUrl":"https://doi.org/10.1002/eji.70003","url":null,"abstract":"<div>\u0000 \u0000 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 in vitro. Moreover, IFN-ω enhances the effector functions of antigen-specific CD8+ T cells primed de novo 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.\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}

引用次数: 0

AK2-Deficient Mice Recapitulate Impaired Lymphopoiesis of Reticular Dysgenesis Patients, but Also Lack Erythropoiesis ak2缺陷小鼠重现网状发育不良患者的淋巴生成受损，但也缺乏红细胞生成

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-07-14 DOI: 10.1002/eji.202451466

Rebekka Waldmann, Franziska Werner, Alpaslan Tasdogan, Felix Immanuel Maier, Ursula Kohlhofer, Irene Gonzalez-Menendez, Leticia Quintanilla de Fend, Amrit Kaur Puarr, Ruth Maree Arkell, Anselm Enders, Manfred Hoenig, Hubert Schrezenmeier, Hans Joerg Fehling, Klaus Schwarz, Ulrich Pannicke

{"title":"AK2-Deficient Mice Recapitulate Impaired Lymphopoiesis of Reticular Dysgenesis Patients, but Also Lack Erythropoiesis","authors":"Rebekka Waldmann, Franziska Werner, Alpaslan Tasdogan, Felix Immanuel Maier, Ursula Kohlhofer, Irene Gonzalez-Menendez, Leticia Quintanilla de Fend, Amrit Kaur Puarr, Ruth Maree Arkell, Anselm Enders, Manfred Hoenig, Hubert Schrezenmeier, Hans Joerg Fehling, Klaus Schwarz, Ulrich Pannicke","doi":"10.1002/eji.202451466","DOIUrl":"https://doi.org/10.1002/eji.202451466","url":null,"abstract":"Reticular dysgenesis (RD) is a rare genetic disorder caused by mutations in the adenylate kinase 2 (AK2) gene. It is characterized by a T−B− severe combined immunodeficiency, agranulocytosis, and sensorineural deafness. We established and characterized a haematopoiesis-specific conditional Ak2-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 Ak2-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.","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}

引用次数: 0

Cover Story: Eur. J. Immunol. 7'25 封面故事：欧元。[j] .免疫学杂志。7'25 .

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-07-10 DOI: 10.1002/eji.70005

引用次数: 0