European Journal of Immunology最新文献_第3页

Sustained Lung Inflammation Post-SARS-CoV-2 Infection in Mice Is Associated with Increased Pulmonary T Cells 小鼠感染sars - cov -2后持续肺部炎症与肺T细胞增加有关

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-08-24 DOI: 10.1002/eji.70043

Sophie Y. Guan, Patricia P. Ogger, Ana Farias, Minerva Garcia Martín, Joy Nakawesi, Olivia Bedard, Candice Baker, Nadia Rosenthal, Cecilia Johansson

{"title":"Sustained Lung Inflammation Post-SARS-CoV-2 Infection in Mice Is Associated with Increased Pulmonary T Cells","authors":"Sophie Y. Guan, Patricia P. Ogger, Ana Farias, Minerva Garcia Martín, Joy Nakawesi, Olivia Bedard, Candice Baker, Nadia Rosenthal, Cecilia Johansson","doi":"10.1002/eji.70043","DOIUrl":"https://doi.org/10.1002/eji.70043","url":null,"abstract":"Many SARS-CoV-2 patients experience chronic pulmonary symptoms and long-term inflammation despite viral clearance. While these clinical manifestations have been linked to the dysregulation of the adaptive immune response, the underlying immunopathology remains poorly understood due to a lack of suitable animal models. To investigate long-term pulmonary consequences of SARS-CoV-2 infection, we used a genetic cross of 129 mice and C57BL/6 (B6)-K18-hACE2 transgene mice, a model previously shown to survive infection. 129xB6-K18-hACE2 mice or littermate controls were infected with a low dose (5 × 102 PFU) of ancestral SARS-CoV-2. Complete viral clearance and full recovery from weight loss occurred by day 8 post-infection. However, prolonged inflammation in the lung and airways persisted up to day 28 post-infection and was associated with the presence of CD4+ and CD8+ T cells, particularly CD8+ effector T cells. This model may therefore prove valuable for further understanding of drivers of long-term lung inflammation and for testing therapeutic strategies and clinically relevant interventions that can target long-term pulmonary inflammation following SARS-CoV-2 infection.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894139","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

SOCS Proteins: Key Players in Immune Regulation During SARS-CoV-2 Infection SOCS蛋白：SARS-CoV-2感染期间免疫调节的关键参与者

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-08-22 DOI: 10.1002/eji.202451645

Juber Herrera-Uribe, Nigel J. Stevenson

引用次数: 0

Mast Cell Phenotypic Heterogeneity Impacts the Interplay with Pathogenic Salmonella Typhimurium Bacteria 肥大细胞表型异质性影响致病性鼠伤寒沙门菌的相互作用

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-08-21 DOI: 10.1002/eji.70040

Christopher von Beek, Grisna I. Prensa, Julia H. M. Andersson, Gunnar Pejler, Mikael E. Sellin

{"title":"Mast Cell Phenotypic Heterogeneity Impacts the Interplay with Pathogenic Salmonella Typhimurium Bacteria","authors":"Christopher von Beek, Grisna I. Prensa, Julia H. M. Andersson, Gunnar Pejler, Mikael E. Sellin","doi":"10.1002/eji.70040","DOIUrl":"https://doi.org/10.1002/eji.70040","url":null,"abstract":"Mast cells (MCs) lodge within barrier tissues and respond to infectious microbes. Recent work demonstrated that MCs differentiate their cytokine response to extracellular versus invasive Gram-negative enterobacteria by a two-step activation mechanism that integrates Toll-like-receptor (TLR) sensing with signals elicited by type-III-secretion-system (TTSS) effectors during bacterial invasion. However, multiple MC subtypes exist, and it remains unclear how their phenotypic heterogeneity impacts microbial interactions. We find that murine MCs maintained in IL-3, or differentiated toward a connective-tissue phenotype (CT-MCs), respond potently to the enteropathogen Salmonella enterica Typhimurium (S.Tm) through two-step activation, with the TLR component explained by functional TLR4 and TLR2. By contrast, murine mucosal mast cells (M-MCs) express insignificant levels of these TLRs, therefore being unresponsive to extracellular S.Tm, but still mounting a response to invasive bacteria. Following invasion, MC granule maintenance by serglycin restricts S.Tm vacuolar and cytosolic colonization. Notably, this has no impact on the cytokine release from infected MCs, thus uncoupling S.Tm´s intracellular life-cycle from the MC cytokine response. Finally, human LUVA MCs employ a variant of two-step activation where TLR2/6 signaling combines with the TTSS-elicited signals. Together, this study explains how MC subtypes can respond differently to S.Tm-infection depending on their TLR expression and granule features.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881121","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

TLR9-Driven S-Palmitoylation in Dendritic Cells Reveals Immune and Metabolic Protein Targets 树突状细胞中tlr9驱动的s -棕榈酰化揭示了免疫和代谢蛋白靶点

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-08-19 DOI: 10.1002/eji.70039

Juan N. Quiroz, Malte Sielaff, Daria Kondrateva, Fatima Boukhallouk, Gloria J. Godoy, Cecilia R. Molina, Brecht Moonen, Claudia C. Motran, Jeroen Bogie, Hugo D. Luján, Stefan Tenzer, Tim Sparwasser, Luciana Berod

{"title":"TLR9-Driven S-Palmitoylation in Dendritic Cells Reveals Immune and Metabolic Protein Targets","authors":"Juan N. Quiroz, Malte Sielaff, Daria Kondrateva, Fatima Boukhallouk, Gloria J. Godoy, Cecilia R. Molina, Brecht Moonen, Claudia C. Motran, Jeroen Bogie, Hugo D. Luján, Stefan Tenzer, Tim Sparwasser, Luciana Berod","doi":"10.1002/eji.70039","DOIUrl":"https://doi.org/10.1002/eji.70039","url":null,"abstract":"Dendritic cells (DCs) rely on Toll-like receptor 9 (TLR9) to detect unmethylated CpG motifs in microbial DNA, triggering essential immune responses. While the downstream signaling pathways of TLR9 activation are well characterized, their impact on S-palmitoylation is unknown. S-palmitoylation, involving the reversible attachment of palmitic acid to cysteine residues, plays a crucial role in regulating protein function and is catalyzed by the ZDHHC family of palmitoyl-acyltransferases (PATs). In this study, we investigated the S-palmitoylated proteome of bone marrow-derived GM-CSF DCs (GM-DCs) at resting and following TLR9 activation with CpGB. Using the click-chemistry-compatible analog 17-octadecynoic acid (17-ODYA) and mass spectrometry (MS)-based proteomics, we characterized dynamic remodeling of S-palmitoylation in response to TLR9 activation. This included enrichment of targets involved in immune and metabolic pathways. Transcriptomic analysis of mice and human DCs revealed TLR9-driven modulation of PAT-encoding genes. Subsequently, we explored the contribution of Zdhhc9 expression to the regulation of S-palmitoylation in DCs. Using gene knockout approaches, we identified candidate protein targets potentially linked to ZDHHC9 activity. Interestingly, modulation of Zdhhc9 expression alone did not influence DC maturation, suggesting that other PATs might compensate for its activity. Together, our findings reveal a novel layer of regulation in TLR9 signaling mediated by S-palmitoylation.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869601","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

Human T Cell Responses to Flavivirus Vaccines 人类T细胞对黄病毒疫苗的反应

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-08-17 DOI: 10.1002/eji.70027

David Wullimann, Hans-Gustaf Ljunggren

{"title":"Human T Cell Responses to Flavivirus Vaccines","authors":"David Wullimann, Hans-Gustaf Ljunggren","doi":"10.1002/eji.70027","DOIUrl":"https://doi.org/10.1002/eji.70027","url":null,"abstract":"Flaviviruses are major human pathogens that continue to pose a global health threat, and vaccination is an effective strategy to protect against disease from several flaviviruses. Flavivirus vaccines are believed to confer protection primarily through antibody responses; however, the role of T cells in vaccine immunity remains less explored despite demonstrated contribution in the response to natural infection. This review examines T cell responses induced by licensed or developing flavivirus vaccines, their contribution to protection, and key findings highlighting the importance of cellular immunity. We discuss the role of memory T cells, including CD4+ and CD8+ subsets, in flavivirus vaccine-induced immunity and compare the immunogenicity of live attenuated versus inactivated vaccines. We also discuss the significance of T cell immunity, cross-reactivity, and vaccine platform design in shaping durable and broad protection. Additionally, we broaden the discussion toward other human RNA viruses, including the influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A better understanding of the role of T cell immunity will be essential for optimizing the use of current flavivirus vaccines and developing next-generation approaches capable of providing long-lasting immunity against emerging and re-emerging flavivirus threats.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861933","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

BMP Signaling Alleviates Allergic Airway Inflammation by Controlling Group 2 Innate Lymphoid Cells Homeostasis BMP信号通过控制2组先天淋巴样细胞稳态减轻过敏性气道炎症

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-08-17 DOI: 10.1002/eji.70038

Shan Yue, Huihui Li, Zhiqiang Yan, Mengying Xie, Mengyuan Dai, Mingying Zhang, Wei Xu

{"title":"BMP Signaling Alleviates Allergic Airway Inflammation by Controlling Group 2 Innate Lymphoid Cells Homeostasis","authors":"Shan Yue, Huihui Li, Zhiqiang Yan, Mengying Xie, Mengyuan Dai, Mingying Zhang, Wei Xu","doi":"10.1002/eji.70038","DOIUrl":"https://doi.org/10.1002/eji.70038","url":null,"abstract":"<div>\u0000 \u0000 Recent studies have highlighted the important role of bone morphogenetic proteins (BMPs) in immunoregulation. Our earlier work identified the expression of BMP receptors on lymphoid progenitors and group 2 innate lymphoid cells (ILC2s) in the bone marrow. However, the precise function of BMP signaling in the development and activity of ILC2s remains unclear. This study aimed to investigate whether BMP signaling regulates the generation of ILC2s and their effector functions during lung airway inflammation. We generated BMP receptor 2 (BMPR2) conditional knockout (CKO) mice to analyze ILC2 development and function. We found that BMPR2 deficiency led to an increased number of ILC2s in the lung at steady state, primarily due to enhanced cell proliferation. This expansion resulted in aggravation of early type 2 response in a papain-induced allergic airway inflammation model. BMP4 restrained the proliferation of ILC2s in vitro and in vivo through activation of the canonical BMP signaling pathway. Administration of BMP4 alleviated papain-induced airway inflammation in control mice, whereas this therapeutic effect was abolished in BMPR2 conditional knockout mice. In conclusion, our study demonstrated that BMP signaling regulates allergic airway inflammation by controlling ILC2s homeostasis.\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861935","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

Booster Injection with Birch Pollen Extract Activates B-Cellular Memory Responses in Patients Having Completed Allergen Immunotherapy 桦树花粉提取物增强注射激活患者完成过敏原免疫治疗的b细胞记忆反应

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-08-17 DOI: 10.1002/eji.70034

Carolin Baum, Christian Möbs, Wolfgang Pfützner

{"title":"Booster Injection with Birch Pollen Extract Activates B-Cellular Memory Responses in Patients Having Completed Allergen Immunotherapy","authors":"Carolin Baum, Christian Möbs, Wolfgang Pfützner","doi":"10.1002/eji.70034","DOIUrl":"https://doi.org/10.1002/eji.70034","url":null,"abstract":"Allergen immunotherapy (AIT) of patients with IgE-mediated allergy results in the synthesis of blocking IgG antibodies mediating allergen tolerance. However, as antibody concentrations wane after stopping AIT, tolerance may be lost. The impact of a single booster allergen application on B-cellular memory in AIT-treated birch pollen (BP)-allergic patients was investigated. Twenty-five patients with BP allergy who finished AIT 3–12 years ago received one allergen injection approximately 4 months prior to the next BP season. We determined peripheral Bet v 1-specific IgG-secreting cells (ASC) by ELISPOT analysis and BP-specific IgG, IgG4, and IgE serum antibodies by ImmunoCAP, and the allergen-blocking capacity of IgG/IgG4 antibodies by ELIFAB assay. Clinical responses were assessed by visual analog scales. Immunological findings were compared with the primary B cell response of 12 BP-allergic patients receiving conventional AIT. Bet v 1-specific ASC significantly increased 2–4 weeks after BP-injection, accompanied by enhanced levels of both BP-specific IgG/IgG4 antibodies and allergen-blocking serum activity. Compared with conventional up-dosing, a single booster vaccination led to a markedly stronger B cell response after 4 weeks. Allergen booster injection activates B-cellular memory associated with blocking IgG/IgG4 antibodies, pointing to reinforcement of allergen tolerance after completion of AIT.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861934","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

Mast Cells Are Not Essential for Pubertal Mammary Gland Branching 肥大细胞不是青春期乳腺分支所必需的

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-08-17 DOI: 10.1002/eji.70036

Simran Kapoor, Clara M. Munz, Jimmy Marsden, Cyril Carvalho, Holly Tinsley, Marlene Magalhaes Pinto, Bert Malengier-Devlies, Solvig Becker, Guillaume Seuzaret, Katelyn Patatsos, Ramazan Akyol, Amy B. Pederson, Gillian Wilson, Marc Dalod, Rebecca Gentek

{"title":"Mast Cells Are Not Essential for Pubertal Mammary Gland Branching","authors":"Simran Kapoor, Clara M. Munz, Jimmy Marsden, Cyril Carvalho, Holly Tinsley, Marlene Magalhaes Pinto, Bert Malengier-Devlies, Solvig Becker, Guillaume Seuzaret, Katelyn Patatsos, Ramazan Akyol, Amy B. Pederson, Gillian Wilson, Marc Dalod, Rebecca Gentek","doi":"10.1002/eji.70036","DOIUrl":"https://doi.org/10.1002/eji.70036","url":null,"abstract":"Mast cells are long-lived, tissue-resident immune cells of the myeloid lineage with cardinal functions in allergy and atopic disease. They are now increasingly recognized also for protective roles, for example against infections and venoms. Other functions originally assigned to mast cells in development and physiology, however, have been refuted, and for yet others, the true contribution of mast cells remains uncertain. Mast cells have been implicated in promoting ductal branching in the pubertal mammary gland, the organ that produces and secretes milk in mammals, but these findings are based on mouse models that are not mast cell-specific. In this study, we therefore re-addressed the impact of mast cells on mammary gland branching using several complementary genetic models, including a newly generated transgenic mouse line (Ms4a2lsl-hDTR). We report that neither constitutive deficiency of mast cells, nor their conditional ablation induced at puberty affects mammary gland branching. Our results thus dispute that mast cells promote this process in mice, at least in a unique and non-redundant manner. This study adds to a growing body of work clarifying the biological roles of mast cells and further expands the toolbox available to the field of mast cell research.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861936","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

The Streptomyces Metabolite Thiostrepton Inhibits Regulatory T Cell Differentiation and Function to Boost Antitumor Immune Responses 链霉菌代谢物硫链顿抑制调节性T细胞分化和增强抗肿瘤免疫反应的功能

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-08-17 DOI: 10.1002/eji.70035

Luana Silva, Luís Almeida, Fatima Al-Naimi, Daniele Carvalho Nascimento, Aleksandra Lopez Krol, Luis Eduardo Alves Damasceno, Hakim Echchannaoui, José Carlos Alves-Filho, Luciana Berod, Tim Sparwasser

{"title":"The Streptomyces Metabolite Thiostrepton Inhibits Regulatory T Cell Differentiation and Function to Boost Antitumor Immune Responses","authors":"Luana Silva, Luís Almeida, Fatima Al-Naimi, Daniele Carvalho Nascimento, Aleksandra Lopez Krol, Luis Eduardo Alves Damasceno, Hakim Echchannaoui, José Carlos Alves-Filho, Luciana Berod, Tim Sparwasser","doi":"10.1002/eji.70035","DOIUrl":"https://doi.org/10.1002/eji.70035","url":null,"abstract":"Regulatory T cells (Tregs) are associated with enhanced tumor progression and reduced therapy response rates. Therefore, overcoming the Treg-mediated immunosuppressive barrier within the tumor to enhance antitumor immune responses is of central interest to advance cancer immunotherapy. To date, no tools exist that can be exploited to dampen Treg function and differentiation in vivo. Here, we show for the first time that the antibiotic thiostrepton exerts a potent inhibitory effect on Tregs. Mechanistically, thiostrepton disrupts Treg differentiation, reduces the expression of Treg activation markers, and inhibits Treg suppressive functions. Accordingly, using an MC38 tumor model, we demonstrate that thiostrepton treatment reduces the number of intratumoral Foxp3+ Treg cells and prevents tumor growth. These effects are conserved in human T cells, as thiostrepton also inhibits the differentiation of human Tregs. Our findings highlight thiostrepton as a promising Treg-targeting immunomodulatory compound with the potential to enhance antitumor immune responses.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861932","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

Neuro-ILC Interactions in Host Physiology and Defence 神经- ilc在宿主生理和防御中的相互作用

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-08-11 DOI: 10.1002/eji.70037

Cristina Godinho-Silva, Miguel Rendas, Henrique Veiga-Fernandes

引用次数: 0