European Journal of Immunology最新文献_第3页

A New Immunofluorescence Assay Allows the Sensitive Detection of Anti-Cytosolic 5′-Nucleotidase 1A Autoantibodies 一种新的免疫荧光法可以灵敏地检测抗胞质5′-核苷酸酶1A自身抗体。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-03-29 DOI: 10.1002/eji.70181

Fleur N. Brinkman, Isa G. A. Verlangen, Filine Swets, Ger J. M. Pruijn

引用次数: 0

Post-Acute Sequelae Patients with Severe COVID-19 History Show a Prolonged Inflammatory, Vascular Injury Pattern 有严重COVID-19病史的急性后后遗症患者表现为长期炎症、血管损伤模式。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-03-29 DOI: 10.1002/eji.70169

Louisa Ruhl, Isabell Pink, Evgeny Chichelnitskiy, Nora Drick, Andrea Sauer, Lennart Boblitz, Kerstin Beushausen, Jana Keil, Anna-Lena Ullrich, Julius Schmidt, Marius M. Hoeper, Tobias Welte, Jenny F. Kühne, Christine S. Falk

{"title":"Post-Acute Sequelae Patients with Severe COVID-19 History Show a Prolonged Inflammatory, Vascular Injury Pattern","authors":"Louisa Ruhl, Isabell Pink, Evgeny Chichelnitskiy, Nora Drick, Andrea Sauer, Lennart Boblitz, Kerstin Beushausen, Jana Keil, Anna-Lena Ullrich, Julius Schmidt, Marius M. Hoeper, Tobias Welte, Jenny F. Kühne, Christine S. Falk","doi":"10.1002/eji.70169","DOIUrl":"10.1002/eji.70169","url":null,"abstract":"SARS-CoV-2 infection can lead to persistent symptoms (i.e., long/post-COVID), especially in unvaccinated individuals. Little is known about the sustained impact of acute severe COVID-19 on immune signatures and long/post-COVID symptoms, often associated with cardiovascular events and pulmonary impairment. The longitudinal cohort (LC) was obtained from N = 46 patients with previous severe COVID-19 and prior to SARS-CoV-2 vaccination, collected over 5 visits up to 12 months after discharge (n = 139). Long/post-COVID status was assessed by lung function and fatigue scores. Blood was analysed regarding immune cell profiles, SARS-CoV-2 antibodies, and autoantigens. LC patients were compared with 39 acute severe COVID-19 ICU patients and 28 unexposed pre-pandemic donors (UE) and correlated with clinical parameters. LC patients exhibited long-term decreased CD4+/CD8+ T cell ratio, differentiation from naïve to TEMRA, CD57+CCR7− memory, and HLA-DR+CD38+ activated CD4+ and CD8+ T cells. LC plasma profiles displayed elevated levels of markers for chronic inflammation and endothelial injury. Chronic inflammatory chemokines and cardiovascular markers remained high. These markers and autoantibodies against centromere structures negatively correlated with lung function. At 1-year post-discharge, LC patients with a COVID-19 ICU history displayed sustained significant changes in their immune profile at cellular and inflammatory levels, revealing signatures of persistent inflammation and endothelial injury.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571474","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

Irgm1 Restrains CD8+ T Cell Cytokine Production and Apoptosis via Cell-Extrinsic Regulation of Type I Interferon Signaling Irgm1通过I型干扰素信号的细胞外源性调节抑制CD8+ T细胞细胞因子的产生和凋亡

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-03-29 DOI: 10.1002/eji.70113

Caitlyn T. Molloy, Yazan Alwarawrah, Jonathan A. Cohen, Brian E. Fee, Jason K. Whitmire, Gregory A. Taylor, Nancie J. MacIver

{"title":"Irgm1 Restrains CD8+ T Cell Cytokine Production and Apoptosis via Cell-Extrinsic Regulation of Type I Interferon Signaling","authors":"Caitlyn T. Molloy, Yazan Alwarawrah, Jonathan A. Cohen, Brian E. Fee, Jason K. Whitmire, Gregory A. Taylor, Nancie J. MacIver","doi":"10.1002/eji.70113","DOIUrl":"10.1002/eji.70113","url":null,"abstract":"<div>\u0000 \u0000 Immunity-related GTPases (IRGs) are a family of proteins that maintain cellular homeostasis by promoting autophagy and mitophagy. Mutations in human IRGM and genetic deletion of mouse Irgm1 have been linked to increased severity of inflammatory bowel disease, cancer, sepsis, and various infections. While IRGM/Irgm1 are known cell-intrinsic regulators of inflammation, their roles in T cell function remain poorly understood. We previously demonstrated that Irgm1 deficiency leads to increased production of proinflammatory mediators, including Granzyme B and interferon-γ, and increased apoptosis in CD8+ T cells. Here, we show that Irgm1 deficiency also alters Granzyme B production and impairs virus-specific CD8+ T cell responses during lymphocytic choriomeningitis virus (LCMV) infection. Using T cell-specific Irgm1 knockout mice and adoptive transfer experiments, we unexpectedly found that Irgm1 regulates CD8+ T cell responses through a cell-extrinsic mechanism. Transcriptomic and genetic analyses identified type I interferons (IFNs) as key mediators of this effect. These findings reveal a previously unrecognized, cell-extrinsic role for Irgm1 in regulating CD8+ T cell survival and function by modulating the inflammatory environment. Our results suggest that IRGM/Irgm1 acts as a critical immune rheostat, restraining pathological inflammation and modulating T cell responses in infection and autoimmunity.\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571496","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

Selective Depletion of Autoreactive Plasma Cells as a Novel Strategy to Treat Acetylcholine Receptor Antibody-Positive Myasthenia Gravis 选择性消耗自身反应性浆细胞作为治疗乙酰胆碱受体抗体阳性重症肌无力的新策略。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-03-29 DOI: 10.1002/eji.70166

Laleh Khodadadi, Deborah Puppe, Dilara S. Cirillo, Carolina Martinez-Cingolani, Jens Klotsche, Andreas Pelz, Siegfried Kohler, Qingyu Cheng, Konstantinos Lazaridis, Michael Fichtner, Jan Pille, Andrey Kruglov, Marina Bondareva, Tobias Alexander, Andreas Radbruch, Andreas Meisel, Falk Hiepe

{"title":"Selective Depletion of Autoreactive Plasma Cells as a Novel Strategy to Treat Acetylcholine Receptor Antibody-Positive Myasthenia Gravis","authors":"Laleh Khodadadi, Deborah Puppe, Dilara S. Cirillo, Carolina Martinez-Cingolani, Jens Klotsche, Andreas Pelz, Siegfried Kohler, Qingyu Cheng, Konstantinos Lazaridis, Michael Fichtner, Jan Pille, Andrey Kruglov, Marina Bondareva, Tobias Alexander, Andreas Radbruch, Andreas Meisel, Falk Hiepe","doi":"10.1002/eji.70166","DOIUrl":"10.1002/eji.70166","url":null,"abstract":"Myasthenia gravis (MG) is a chronic autoimmune disease mediated by autoantibodies targeting the neuromuscular junction and leading to muscle weakness. Although there are autoantibodies of different specificities, most MG patients have autoantibodies directed against the nicotinic acetylcholine receptor (AChR), in particular against the extracellular domain of the α1 subunit (αECD), containing the main immunogenic region (MIR). Here, we demonstrate an original approach to selectively deplete plasma cells secreting autoantibodies targeting αECD. An antibody-mediated cytotoxicity-engager (ACE) consisting of an anti-hCD38-antibody conjugated to hAChR αECD (αECD) was used to deplete hAChR αECD-specific cells selectively in vivo. The reduction of pathogenic cells was accompanied by lower antibody titers, a reduction of MG disease score, protection of grip strength, and maintenance of body weight. Notably, antibody-secreting cells that are nonspecific for hAChR αECD were not affected. The resulting amelioration of MG pathology in ACE-treated animals highlights the decisive role of αECD-antibodies in the pathogenesis of MG and the clinical relevance of the novel therapeutic strategy.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571487","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

Systemic Type I Interferon Blockade Mitigates Insulin Resistance in a Preclinical Model of Psoriasis 全身性I型干扰素阻断减轻银屑病临床前模型中的胰岛素抵抗。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-03-29 DOI: 10.1002/eji.70160

Bishnu Prasad Sinha, Purbita Bandopadhyay, Md. Asmaul Hoque, Chinky Shiu Chen Liu, Suravi Mukherjee, Ranit D'Rozario, Shreya Roy, Rituparna Jana, Shrestha Pattanayak, Jafar Sarif, Dipyaman Ganguly

{"title":"Systemic Type I Interferon Blockade Mitigates Insulin Resistance in a Preclinical Model of Psoriasis","authors":"Bishnu Prasad Sinha, Purbita Bandopadhyay, Md. Asmaul Hoque, Chinky Shiu Chen Liu, Suravi Mukherjee, Ranit D'Rozario, Shreya Roy, Rituparna Jana, Shrestha Pattanayak, Jafar Sarif, Dipyaman Ganguly","doi":"10.1002/eji.70160","DOIUrl":"10.1002/eji.70160","url":null,"abstract":"<div>\u0000 \u0000 Psoriasis is a cutaneous autoimmune disease with worldwide prevalence. In situ activation of skin-infiltrating plasmacytoid dendritic cells (pDCs) leading to local induction of type I interferons (IFNs) is a crucial innate initiation event in psoriasis. Psoriatic patients also have notable susceptibility to the development of metabolic syndrome, especially systemic insulin resistance. Interestingly, a crucial role of systemic and metabolic tissue-restricted induction of type I IFNs is now established in metabolic syndrome. We aimed at exploring whether systemic type I IFN abundance contributes to metabolic derangements in psoriatic patients as well. We developed a preclinical murine model of chronic psoriasis that develops systemic insulin resistance, accompanied by a chronic low-grade systemic inflammation. Then we showed that systemic ablation of type I IFN signaling, using a monoclonal antibody against type I IFN receptor IFNAR1, can mitigate the metabolic dysregulation in this preclinical model of psoriasis-associated insulin resistance. Thus, we report a hitherto unknown role of systemic type I IFN abundance in driving systemic insulin resistance and metabolic dysregulations in psoriasis.\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571552","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

Depletion of Neonatal Neutrophilic Cells Worsens the Outcome of E. coli Sepsis in Newborn Mice 新生儿中性粒细胞耗竭恶化新生儿小鼠大肠杆菌败血症的结局。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-03-29 DOI: 10.1002/eji.70171

Julian Schwarz, Janine Hebel, Stefanie Dietz-Ziegler, Jessica Rühle, Trim Lajqi, Thorsten Orlikowsky, Christian F. Poets, Christian Gille, Natascha Köstlin-Gille

{"title":"Depletion of Neonatal Neutrophilic Cells Worsens the Outcome of E. coli Sepsis in Newborn Mice","authors":"Julian Schwarz, Janine Hebel, Stefanie Dietz-Ziegler, Jessica Rühle, Trim Lajqi, Thorsten Orlikowsky, Christian F. Poets, Christian Gille, Natascha Köstlin-Gille","doi":"10.1002/eji.70171","DOIUrl":"10.1002/eji.70171","url":null,"abstract":"Neonates are particularly susceptible to infections because of a reduced ability to fight bacterial pathogens while simultaneously exhibiting enhanced inflammatory damage. Neonatal neutrophilic cells (NNC) are a heterogeneous population of innate immune cells, which differ substantially from adults. They display functional deficits in pro-inflammatory responses and include a suppressive subpopulation known as myeloid-derived suppressor cells (MDSC). It remains unclear whether pro- or anti-inflammatory properties of NNC predominate immediately after birth. This study aimed to clarify the role of neutrophilic cells in neonatal murine sepsis. We established a neonatal mouse model of E. coli-sepsis and depleted NNC using an anti-Ly6G antibody to assess mortality, bacterial load, cytokine responses, and immune cell composition. A dose of 30,000 CFU E. coli resulted in a 67% survival rate in neonatal mice with litters of 5–6 pups, while mortality increased in larger litters. NNC-depletion significantly increased mortality and systemic inflammation during neonatal sepsis, whereas bacterial load was only minimally affected. Other immune cell populations remained unchanged. E. coli sepsis induced pronounced neutrophil infiltration into organs of adults, whereas neonates exhibit reduced numbers of NNC in affected organs. Overall, our findings suggest that NNC-mediated control of inflammation may protect neonates from lethal sepsis.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571534","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

Deletion of Lymphatic PD-L1 Protects Mice From Severe Autoimmune Encephalitis 淋巴PD-L1缺失保护小鼠免受严重自身免疫性脑炎

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-03-29 DOI: 10.1002/eji.70175

Ziyuan Wang, Elèni Meuffels, Christian Ashworth, Emma Reynaud, Shruthi Hemanna, Burkhard Becher, Michael Detmar, Sarah Mundt, Lothar C. Dieterich

引用次数: 0

Prophylactic Inhaled Pattern Recognition Receptor Agonists Reprogram Lung Epithelial Response and Prevent Type 2 Allergic Inflammation 预防性吸入模式识别受体激动剂重编程肺上皮反应和预防2型过敏性炎症。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-03-27 DOI: 10.1002/eji.70172

Mbaya Ntita, Celine Shuet Lin Kong, Dalia Hassan, Richa Nayak, Jezreel Pantaleón García, Yongxing Wang, Jichao Chen, Scott E. Evans

{"title":"Prophylactic Inhaled Pattern Recognition Receptor Agonists Reprogram Lung Epithelial Response and Prevent Type 2 Allergic Inflammation","authors":"Mbaya Ntita, Celine Shuet Lin Kong, Dalia Hassan, Richa Nayak, Jezreel Pantaleón García, Yongxing Wang, Jichao Chen, Scott E. Evans","doi":"10.1002/eji.70172","DOIUrl":"10.1002/eji.70172","url":null,"abstract":"Prophylactic inhalation of the synergistic agents ODN M362 and Pam2CSK4 (“Pam2ODN”) protects mice against allergic lung disease, including allergic inflammation caused by house dust mite (HDM). By preventing sensitization, Pam2ODN reduces HDM-induced eosinophilic and lymphocytic inflammation. How Pam2ODN affects interactions among lung epithelial cells, dendritic cells, and T cells to prevent eosinophilic lung inflammation remains unclear. In the present study, we show that a single inhaled dose of Pam2ODN before HDM sensitization reduces airway Th2 polarization without affecting Th1 or Treg responses. Furthermore, Pam2ODN pretreatment inhibits the recruitment of lung monocyte-derived dendritic cells (moDCs) and conventional Type 2 dendritic cells (DC2s), while preventing the HDM-induced decrease in conventional Type 1 dendritic cells (DC1s). Bulk RNA-seq of the whole lung reveals that Pam2ODN pretreatment restricts the expression of proinflammatory transcripts induced by HDM sensitization. This tolerogenic effect is also reflected at the single-cell level in lung epithelial cells, where proinflammatory transcripts, pathways, and chromatin accessibility are inhibited. These results indicate that Pam2ODN reprograms lung epithelial cells to attenuate allergen-induced Th2-promoting cytokines and DCs while maintaining the population of protective DC1s. These findings suggest a strategy to mitigate chronic allergic lung diseases.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13022946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147525084","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

No Correlation Between Interferon Signaling and Cytosolic Mitochondrial DNA/RNA Leakage in Cultured Skin Fibroblasts of Patients With Mitochondrial Diseases 线粒体疾病患者皮肤成纤维细胞中干扰素信号与胞质线粒体DNA/RNA泄漏的相关性研究

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-03-27 DOI: 10.1002/eji.70176

Manon Marchais, Alessandra Pennisi, Alexandre Pierga, Alice Lepelley, Nicolas Cagnard, Christine Bole, Patrick Nitschke, Mohamed Hamici, Frédéric Rieux-Laucat, Manuel Schiff, Arnold Munnich, Agnès Rötig

{"title":"No Correlation Between Interferon Signaling and Cytosolic Mitochondrial DNA/RNA Leakage in Cultured Skin Fibroblasts of Patients With Mitochondrial Diseases","authors":"Manon Marchais, Alessandra Pennisi, Alexandre Pierga, Alice Lepelley, Nicolas Cagnard, Christine Bole, Patrick Nitschke, Mohamed Hamici, Frédéric Rieux-Laucat, Manuel Schiff, Arnold Munnich, Agnès Rötig","doi":"10.1002/eji.70176","DOIUrl":"10.1002/eji.70176","url":null,"abstract":"Mitochondria have long been known to be involved in the regulation of innate immune response. We questioned whether cultured skin fibroblasts of patients suffering from mitochondrial diseases are valuable biological resources for the study of interferon signaling. Expression of interferon-stimulated genes was measured in control cells supplemented with interferon and in cultured fibroblasts of patients carrying pathogenic variants in mitochondrial disease-causing genes. Control fibroblasts showed a strong expression of interferon-stimulated genes in response to interferon, but only 43% of patients’ fibroblasts displayed increased interferon stimulated genes scores. Cytosolic mitochondrial DNA and RNA were quantified by immunofluorescence and confocal microscopy. No correlation between elevated interferon response and cytosolic mitochondrial DNA or RNA release could be established. We found that cultured skin fibroblasts represent a valuable biological resource for the investigation of interferon signaling, but that abnormal interferon signaling is not always observed in patients with mitochondrial diseases. At variance to gene silencing in control fibroblasts, the lack of correlation between elevated interferon response and cytosolic mitochondrial DNA or RNA leakage in patients’ fibroblasts questions the relevance of cellular models as illustrators of pathological situations in humans.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13022800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147525098","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. 4'26 封面故事：欧元。[j] .免疫学杂志

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-03-27 DOI: 10.1002/eji.70184

引用次数: 0