European Journal of Immunology最新文献_第2页

Loss of PI3Kδ Activity Drives Autoimmune Colitis by Impairing Extrathymic Treg Differentiation PI3Kδ活性的丧失通过损害胸腺外Treg分化驱动自身免疫性结肠炎。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-10-06 DOI: 10.1002/eji.70069

Ee Lyn Lim, Yamin Qian, Fuminori Sugihara, Atsushi Tanaka, Shimon Sakaguchi

{"title":"Loss of PI3Kδ Activity Drives Autoimmune Colitis by Impairing Extrathymic Treg Differentiation","authors":"Ee Lyn Lim, Yamin Qian, Fuminori Sugihara, Atsushi Tanaka, Shimon Sakaguchi","doi":"10.1002/eji.70069","DOIUrl":"10.1002/eji.70069","url":null,"abstract":"Peripherally derived regulatory T cells (pTregs) have a prominent role in maintaining intestinal immune homeostasis. In cases of phosphoinositide-3-kinase δ (PI3Kδ) inactivation, such as in patients receiving PI3Kδ inhibitor idelalisib as a cancer treatment, breakdown of intestinal immune tolerance occurs frequently in the form of diarrhea and colon inflammation. In a mouse model of systemic PI3Kδ inactivation, both enhancement of antitumor immunity and colitis have been described as a result of Treg impairment. However, in view of the critical role for Tregs in the prevention of systemic autoimmunity, the basis for such tissue-restricted breach of immune tolerance upon loss of PI3Kδ function is not yet understood. We report here that mice lacking PI3Kδ activity do not suffer a general defect in Treg immunosuppression, but specifically fail to develop Helios− pTregs in the colon. We demonstrate reduced extrathymic Treg induction, in vitro and in vivo, from naïve CD4+ T cells with inactive PI3Kδ, along with dysregulation of a tissue-resident phenotype. These results suggest a nonredundant role for PI3Kδ-dependent pTreg differentiation in maintaining tolerance to commensal microbial antigens in the gut.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237466","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

Imaging Mass Cytometry-Based Immune Profiling of Human Peyer's Patches in Patients with Crohn's Disease 克罗恩病患者Peyer's斑块的成像细胞计数免疫分析

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-10-06 DOI: 10.1002/eji.70071

Adrian Huck, Yasmina Rodriguez-Sillke, Christian Bojarski, Désirée Kunkel, Anja A. Kühl, Malte Lehmann, Philip Bischoff, Ulrich Steinhoff, Britta Siegmund, Rainer Glauben

{"title":"Imaging Mass Cytometry-Based Immune Profiling of Human Peyer's Patches in Patients with Crohn's Disease","authors":"Adrian Huck, Yasmina Rodriguez-Sillke, Christian Bojarski, Désirée Kunkel, Anja A. Kühl, Malte Lehmann, Philip Bischoff, Ulrich Steinhoff, Britta Siegmund, Rainer Glauben","doi":"10.1002/eji.70071","DOIUrl":"10.1002/eji.70071","url":null,"abstract":"Lymphoid follicles in the human gut are critical immune hubs, yet their role in Crohn's disease pathogenesis remains poorly understood. Here, we apply multiplexed imaging mass cytometry to spatially profile Peyer's patches and lymphoid follicles in biopsies from healthy controls and Crohn's disease patients with ileitis, isolated colonic involvement, or in remission. Despite tissue heterogeneity, our optimized preprocessing pipeline enabled robust tissue annotation, single-cell phenotyping, and neighbourhood-level analysis. While conventional analysis based on cell frequencies did not distinguish disease states, spatial analysis revealed disease-associated remodelling of lymphoid architecture. Biopsies from colonic Crohn's disease patients showed, within follicles, increased frequencies of activated CD8⁺ T cells and a reduction in naïve T cells, alongside enrichment of B cell–T cell interaction neighbourhoods. These alterations were most pronounced in smaller B-cell patches, suggesting more functionally dynamic immune-cell interactions in compact lymphoid structures. In contrast, Crohn's disease ileitis samples closely resembled healthy tissue, with minimal structural or immune cell perturbations. Our data support a model in which Peyer's patches and lymphoid follicles undergo structural and functional remodelling in response to colonic inflammation. These findings underscore the value of spatially resolved immune profiling to uncover tissue-specific immune dynamics in inflammatory bowel disease.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237475","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

Issue Information: Eur. J. Immunol. 10'25 发行信息：欧元。[j] .免疫学杂志，2010

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-10-03 DOI: 10.1002/eji.70075

引用次数: 0

Cover Story: Eur. J. Immunol. 10'25 封面故事：欧元。[j] .免疫学杂志，2010

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-10-03 DOI: 10.1002/eji.70074

引用次数: 0

Low-Input Assay for Transposase-Accessible Chromatin Identifies Epigenetic Signatures of Liver Group 1 Innate Lymphoid Cells 转座酶可及染色质的低输入试验鉴定肝脏1组先天淋巴样细胞的表观遗传特征。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-10-03 DOI: 10.1002/eji.70066

Kevin Schmid, Robin P. Schenk, Gabriela M. Wiedemann

引用次数: 0

LILRA5 Functions to Induce ROS Production on Innate Immune Cells. LILRA5诱导先天免疫细胞产生ROS的功能

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-10-01 DOI: 10.1002/eji.70079

Zuyi Fu, Matevž Rumpret, Irina Kube-Golovin, Mykola Lyndin, Vera Solntceva, Yuxi Zhao, Anastasia Konieva, Na Liu, Adrian T Press, Stefanie B Flohé, Michael Bauer, Gunther Wennemuth, Bernhard B Singer, Alex J McCarthy

{"title":"LILRA5 Functions to Induce ROS Production on Innate Immune Cells.","authors":"Zuyi Fu, Matevž Rumpret, Irina Kube-Golovin, Mykola Lyndin, Vera Solntceva, Yuxi Zhao, Anastasia Konieva, Na Liu, Adrian T Press, Stefanie B Flohé, Michael Bauer, Gunther Wennemuth, Bernhard B Singer, Alex J McCarthy","doi":"10.1002/eji.70079","DOIUrl":"10.1002/eji.70079","url":null,"abstract":"Activating immune receptors provides mechanisms for phagocytes to elicit important effector functions that promote the killing of microbes. Leukocyte immunoglobulin-like receptor A5 (LILRA5), an orphan immune receptor expressed by human phagocytes and co-localising with FcRγ, remains poorly characterised. To address this, we developed a highly specific anti-LILRA5 monoclonal antibody that has agonistic properties. We show LILRA5 expression on naïve monocytes and neutrophils, and that ligation of LILRA5 stimulates ROS production. While increased LILRA5 transcripts have been associated with sepsis, we also observed increased levels in patients with systemic infection but without sepsis complications. Ex vivo bacterial infection of whole blood did not alter surface LILRA5 expression, but LPS stimulation changed expression levels, indicating that surface LILRA5 expression is dynamic and likely regulated post-transcriptionally, changing responses to different stimuli or over time. Soluble (s)LILRA5 was enhanced in sera from sepsis patients and in supernatants of monocytes that were LPS-stimulated, indicating that shedding of LILRA5 from cell surfaces or that expression of sLILRA5 isoforms provides a mechanism to regulate surface LILRA5 expression levels. Finally, we show that altered surface LILRA5 expression influences LILRA5-induced ROS production capacity. Thus, LILRA5 is a dynamically regulated activating receptor expressed on phagocytes that stimulates ROS production.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 10","pages":"e70079"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145335968","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

Identification and Functional Validation of Novel Pathogenic Variants in Primary Immunodeficiencies. 原发性免疫缺陷新致病变异的鉴定和功能验证。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-10-01 DOI: 10.1002/eji.70057

Arvinden Vr, Geeta Madathil Govindaraj, Aditya Ramdas Iyer, Sangita Paul, Athulya Edavazhippurath, Abhinav Jain, Pragya Gupta, Gauspasha Yusuf Deshmukh, Shivani Singh, Vinodh Saravanakumar, Juhi Bhardwaj, Srishti Sharma, Tancia P Benny, Priya Saravanan, Rahul C Bhoyar, Mohamed Imran, Vigneshwar Senthivel, Mohit Kumar Divakar, Harie Vignesh, Bani Jolly, Aparna Dalvi, Umair Ahmed Bargir, Manisha Madkaikar, Binukumar Bk, Sridhar Sivasubbu, Sivaprakash Ramalingam, Vinod Scaria

{"title":"Identification and Functional Validation of Novel Pathogenic Variants in Primary Immunodeficiencies.","authors":"Arvinden Vr, Geeta Madathil Govindaraj, Aditya Ramdas Iyer, Sangita Paul, Athulya Edavazhippurath, Abhinav Jain, Pragya Gupta, Gauspasha Yusuf Deshmukh, Shivani Singh, Vinodh Saravanakumar, Juhi Bhardwaj, Srishti Sharma, Tancia P Benny, Priya Saravanan, Rahul C Bhoyar, Mohamed Imran, Vigneshwar Senthivel, Mohit Kumar Divakar, Harie Vignesh, Bani Jolly, Aparna Dalvi, Umair Ahmed Bargir, Manisha Madkaikar, Binukumar Bk, Sridhar Sivasubbu, Sivaprakash Ramalingam, Vinod Scaria","doi":"10.1002/eji.70057","DOIUrl":"https://doi.org/10.1002/eji.70057","url":null,"abstract":"Primary immunodeficiency diseases (PIDs) are inherited disorders caused by genetic defects affecting immune function, leading to recurrent infections, autoimmunity, and malignancies. Many PIDs remain genetically uncharacterized, largely due to rare variants with unclear pathogenicity, which complicates the process of establishing an accurate diagnosis. Next-generation sequencing (NGS) technology enables the identification of molecular defects, improving the diagnosis of PIDs. Functional validation of genetic variants identified through PID-related gene screenings is crucial for determining their clinical significance. In this study, we identified five novel variants in PID-related genes in six families using whole-exome sequencing. These variants include FCHO1 (E44K), NCF2 (A206P), NCF2 (c.174 + 1G > A), STAT1 (L199F), and a copy number deletion in LRBA (exon 9-17). Functional validation was performed for four of these variants: STAT1 (L199F) using pSTAT1 assay, NCF2 (A206P and c.174 + 1G > A) by DHR assay, and FCHO1 (E44K) using CRISPR-mediated genome editing. Overall, the present study expands the knowledge of previously unreported variants in primary immunodeficiency.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 10","pages":"e70057"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145335954","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

CD16A Shedding Regulates Innate Cell Engager-Induced Serial Killing by Natural Killer Cells. CD16A脱落调节先天细胞接合物诱导的自然杀伤细胞连环杀伤。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-10-01 DOI: 10.1002/eji.70078

Chiara Zambarda, Karolin Guldevall, Christian Breunig, Damien Toullec, Patrick A Sandoz, Valentina Carannante, Shanshan Xu, Patrick Ross, Kyra Kuhnigk, Niklas Sandström, Jacopo Fontana, Susanne Wingert, Sheena Pinto, Julia Knoch, Alamdar Hussain, Arnika K Wagner, Jens Pahl, Evren Alici, Joachim Koch, Björn Önfelt

{"title":"CD16A Shedding Regulates Innate Cell Engager-Induced Serial Killing by Natural Killer Cells.","authors":"Chiara Zambarda, Karolin Guldevall, Christian Breunig, Damien Toullec, Patrick A Sandoz, Valentina Carannante, Shanshan Xu, Patrick Ross, Kyra Kuhnigk, Niklas Sandström, Jacopo Fontana, Susanne Wingert, Sheena Pinto, Julia Knoch, Alamdar Hussain, Arnika K Wagner, Jens Pahl, Evren Alici, Joachim Koch, Björn Önfelt","doi":"10.1002/eji.70078","DOIUrl":"10.1002/eji.70078","url":null,"abstract":"Natural killer (NK) cells can protect from tumor-transformed cells using a fine-tuned machinery of activating and inhibiting receptors. An important activating receptor is Fc gamma receptor IIIa (FcγRIIIA or CD16A), which can trigger antibody-dependent cellular cytotoxicity (ADCC) when recognizing antibody-opsonized target cells. One strategy to boost ADCC responses may be achieved by inhibiting activation-induced shedding of CD16A from the NK cell surface. However, previous preclinical studies have shown contrasting results regarding the effectiveness and limitations of this approach. Here, microchip-based live cell-imaging was used to assess the consequences of CD16A shedding inhibition on the dynamics of NK cell cytotoxicity. The bispecific innate cell engager acimtamig (AFM13) was superior to IgG1 monoclonal antibodies in ADCC and in increasing the fraction of cytotoxic NK cells and serial killers. Under conditions where CD16A shedding was inhibited, acimtamig still triggered ADCC; however, the ability to promote serial killing was reduced and associated with impaired NK cell detachment from target cells. These results demonstrate that CD16A shedding represents an intrinsic feature of NK cell biology that is critical to sustain the antitumoral cytotoxicity of NK cells. This has implications for CD16A engineering of NK cell products and their combination with CD16A-directed NK cell engagers.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 10","pages":"e70078"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336012","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

Administration of the NOD2 Agonist MDP Reduces Cryptosporidium parvum Infection in Neonatal Mice Through IL-22 Involvement. NOD2激动剂MDP通过参与IL-22减少新生小鼠小隐孢子虫感染

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-10-01 DOI: 10.1002/eji.70080

Mégane Fernandez, Tiffany Pezier, Julien Pichon, Yves Le Vern, Catherine Werts, Sonia Lacroix-Lamandé

{"title":"Administration of the NOD2 Agonist MDP Reduces Cryptosporidium parvum Infection in Neonatal Mice Through IL-22 Involvement.","authors":"Mégane Fernandez, Tiffany Pezier, Julien Pichon, Yves Le Vern, Catherine Werts, Sonia Lacroix-Lamandé","doi":"10.1002/eji.70080","DOIUrl":"10.1002/eji.70080","url":null,"abstract":"At birth, the mucosal immune system of neonates is not fully developed, making them more susceptible to respiratory and intestinal diseases. Previously described host-directed therapies using toll-like receptor (TLR) activation-based strategies have proven effective in controlling neonatal diseases, including cryptosporidiosis. In this study, we investigated the effect of nucleotide-binding oligomerization domain (NOD) receptors stimulation on the control of enteric infection by the protozoan Cryptosporidium parvum in neonatal mice. NOD2 stimulation by intraperitoneal injection of muramyl dipeptide (MDP) resulted in a rapid reduction in the parasite burden. The protective effect was associated with increased pro-inflammatory cytokine and antimicrobial peptide gene expression and a rapid influx of neutrophils to the site of infection, whereas NOD1 stimulation did not show a protective effect. The protective mechanism did not involve microbiota participation but involved IFN-γ and IL-22 cytokines and was associated with increased intestinal epithelium renewal in infected neonates. Our findings showed that stimulating neonatal mice with the bacterial ligand MDP, which targets the NOD2 receptor, actively contributes to the nonspecific clearance of C. parvum infection by eliminating or renewing infected epithelial cells.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 10","pages":"e70080"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12538031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336313","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

TNF Production or TNFR2 Expression Characterize Distinct States of Regulatory T Cells that Cooperate in Treg Expansion in Cancer and Chronic Inflammation 肿瘤坏死因子的产生或TNFR2的表达在肿瘤和慢性炎症中协同Treg扩增的调节性T细胞的不同状态

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-09-21 DOI: 10.1002/eji.70062

Gloria Tucci, Ilenia Pacella, Alessandra Pinzon Grimaldos, Alessandra Rossi, Ilenia Cammarata, Marta Zagaglioni, Giovanna Peruzzi, Valentina Tirelli, Massimo Sanchez, Giuseppe Pietropaolo, Francesca Sozio, Annalisa Del Prete, Valerio Licursi, Vincenzo Barnaba, Silvia Piconese

{"title":"TNF Production or TNFR2 Expression Characterize Distinct States of Regulatory T Cells that Cooperate in Treg Expansion in Cancer and Chronic Inflammation","authors":"Gloria Tucci, Ilenia Pacella, Alessandra Pinzon Grimaldos, Alessandra Rossi, Ilenia Cammarata, Marta Zagaglioni, Giovanna Peruzzi, Valentina Tirelli, Massimo Sanchez, Giuseppe Pietropaolo, Francesca Sozio, Annalisa Del Prete, Valerio Licursi, Vincenzo Barnaba, Silvia Piconese","doi":"10.1002/eji.70062","DOIUrl":"https://doi.org/10.1002/eji.70062","url":null,"abstract":"TNF is a pleiotropic cytokine with immunomodulatory functions mediated by its interaction with the receptor TNFR2, highly expressed by Tregs. However, Tregs can also produce TNF, and an autocrine TNF-TNFR2 loop has been proposed. Here, we describe that both human and mouse Tregs produce TNF in physiological conditions, in several mouse organs, and in mouse models of chronic inflammation and cancer. However, TNF production and TNFR2 expression are differentially distributed: indeed, TNFR2+ and TNFR2− Treg subsets are, respectively, poor and strong TNF producers. The two subsets of TNFR2+ and TNFR2− Tregs partially maintain their different ability to produce TNF when separately stimulated ex vivo. However, when cocultured, the TNFR2+ cells greatly outnumber the TNFR2− counterpart and induce in TNFR2− cells the upregulation of Foxp3 and TNFR2, in association with the transfer of cytoplasmic material. Functionally, TNFR2+ Tregs display superior suppressive activity and survival in vitro, both related to an improved resistance to oxidative stress. Overall, our data indicate that Tregs exist in two states, respectively committed to TNF production or TNF sensing through TNFR2, which cooperate in promoting the suppressive function of the whole Treg pool.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 9","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111107","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