European Journal of Immunology最新文献_第4页

TOX Does Not Drive Sepsis-Induced T-Cell Exhaustion. 毒素不会导致败血症诱导的 T 细胞耗竭

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-15 DOI: 10.1002/eji.202451395

Yingyu Qin, Yilin Qian, Shengqiu Liu, Rong Chen

{"title":"TOX Does Not Drive Sepsis-Induced T-Cell Exhaustion.","authors":"Yingyu Qin, Yilin Qian, Shengqiu Liu, Rong Chen","doi":"10.1002/eji.202451395","DOIUrl":"https://doi.org/10.1002/eji.202451395","url":null,"abstract":"The immune system undergoes profound dysregulation in sepsis, characterized by hyperinflammation in the acute phase followed by long-lasting immunosuppression. T-cell exhaustion has been proposed as one facet of sepsis-related immunosuppression, which is characterized by impaired effector function and continuous expression of PD1. However, the current analysis of T-cell exhaustion in the post-sepsis is inadequate. Our current study has identified a progressive increase in the frequency of CD44+CD11a+ memory T cells during the post-sepsis phase, accompanied by the upregulation of exhaustion markers (PD-1, Lag3, and Tim3) and functional impairments in these cells. TOX is traditionally recognized as a key regulator driving CD8+ T-cell exhaustion in cancer and chronic infection. However, we demonstrate that TOX does not play a critical role in T-cell exhaustion during chronic sepsis but rather is involved in T-cell effector function. Both knockout and \"knockdown\" of TOX failed to alleviate sepsis-induced T-cell exhaustion. Instead, deletion of TOX impaired the effector function of T cells in chronic sepsis, contradicting its impact on short-term TCR engagement. Our study provides a novel insight into sepsis-induced T-cell exhaustion, highlighting the distinct characteristics of T-cell exhaustion programmed by sepsis.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451395"},"PeriodicalIF":4.5,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826999","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

Distinct Tissue-Dependent Composition and Gene Expression of Human Fetal Innate Lymphoid Cells. 人胎儿先天淋巴样细胞的不同组织依赖性组成和基因表达。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-15 DOI: 10.1002/eji.202451150

Inga E Rødahl, Martin A Ivarsson, Liyen Loh, Jeff E Mold, Magnus Westgren, Danielle Friberg, Jenny Mjösberg, Niklas K Björkström, Nicole Marquardt, Douglas F Nixon, Jakob Michaëlsson

引用次数: 0

KIRA6 is an Effective and Versatile Mast Cell Inhibitor of IgE-mediated Activation. KIRA6 是一种有效的多用途肥大细胞抑制剂，能抑制 IgE 介导的活化。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-15 DOI: 10.1002/eji.202451348

Veronika Wunderle, Thomas Wilhelm, Shatha Boukeileh, Jonas Goßen, Michael A Margreiter, Roman Sakurov, Sandro Capellmann, Maike Schwoerer, Nabil Ahmed, Gina Bronneberg, Michel Arock, Christian Martin, Thomas Schubert, Francesca Levi-Schaffer, Giulia Rossetti, Boaz Tirosh, Michael Huber

{"title":"KIRA6 is an Effective and Versatile Mast Cell Inhibitor of IgE-mediated Activation.","authors":"Veronika Wunderle, Thomas Wilhelm, Shatha Boukeileh, Jonas Goßen, Michael A Margreiter, Roman Sakurov, Sandro Capellmann, Maike Schwoerer, Nabil Ahmed, Gina Bronneberg, Michel Arock, Christian Martin, Thomas Schubert, Francesca Levi-Schaffer, Giulia Rossetti, Boaz Tirosh, Michael Huber","doi":"10.1002/eji.202451348","DOIUrl":"https://doi.org/10.1002/eji.202451348","url":null,"abstract":"Mast cell (MC)-driven allergic diseases are constantly expanding and require the development of novel pharmacological MC stabilizers. Allergen/antigen (Ag)-triggered activation via crosslinking of the high-affinity receptor for IgE (FcεRI) is fundamentally regulated by SRC family kinases, for example, LYN and FYN, exhibiting positive and negative functions. We report that KIRA6, an inhibitor for the endoplasmic reticulum stress sensor IRE1α, suppresses IgE-mediated MC activation by inhibiting both LYN and FYN. KIRA6 attenuates Ag-stimulated early signaling and effector functions such as degranulation and proinflammatory cytokine production/secretion in murine bone marrow-derived MCs. Moreover, Ag-triggered bronchoconstriction in an ex vivo model and IgE-mediated stimulation of human MCs were repressed by KIRA6. The interaction of KIRA6 with three MC-relevant tyrosine kinases, LYN, FYN, and KIT, and the potential of KIRA6 structure as a pharmacophore for the development of respective single-, dual-, or triple-specificity inhibitors, was evaluated by homology modeling and molecular dynamics simulations. We found that KIRA6 particularly strongly binds the inactive state of LYN, FYN, and KIT with comparable affinities. In conclusion, our data suggest that the chemical structure of KIRA6 as a pharmacophore can be further developed to obtain an effective MC stabilizer.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451348"},"PeriodicalIF":4.5,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826994","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

Human Genetic GLUT1 Deficiency Results in Impaired T Cellular IFN-γ Production. 人类遗传性GLUT1缺乏导致T细胞IFN-γ产生受损。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-13 DOI: 10.1002/eji.202451066

Renske de Jong, Anandhi Rajendiran, Judit Turyne Hriczko, Sudheendra Hebbar Subramanyam, Alina Rein, Martin Häusler, Thorsten Orlikowsky, Norbert Wagner, Daniel Erny, Kim Ohl, Klaus Tenbrock

引用次数: 0

Activation of STAT6 in Intestinal Epithelial Cells Predisposes to Gut Inflammation. 肠上皮细胞中STAT6的激活易导致肠道炎症。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-13 DOI: 10.1002/eji.202451394

Stefanie Westermann, Daniel Radtke, Lisa Kramer, Stefan Wirtz, David Voehringer

{"title":"Activation of STAT6 in Intestinal Epithelial Cells Predisposes to Gut Inflammation.","authors":"Stefanie Westermann, Daniel Radtke, Lisa Kramer, Stefan Wirtz, David Voehringer","doi":"10.1002/eji.202451394","DOIUrl":"https://doi.org/10.1002/eji.202451394","url":null,"abstract":"Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) often associated with a Type 2 immune response. Although previous reports hint at a role for signal transducer and activator of transcription (STAT) 6 signaling in non-immune cells, the contribution of STAT6-activation particularly in intestinal epithelial cells (IECs) is still unknown. Dextran sodium sulfate (DSS)-induced colitis is a model for UC in mice that we applied here on animals with expression of a constitutively active version of STAT6 in IECs (VillinCre_STAT6vt mice). We report increased pathology and mortality due to enhanced and systemic inflammation in these mice. Bulk RNA sequencing of colonic tissue from naïve VillinCre_STAT6vt mice showed differential expression of more than 140 genes compared to control mice. Gene set enrichment analysis revealed STAT6-regulated expression of the unfolded protein response, MTORC- and MYC-signaling, and protein secretion pathways. A comparison of gene expression in the colon of naïve VillinCre_STAT6vt mice and a human single-cell RNA sequencing dataset of a patient cohort with IBD revealed overlapping changes in the epithelial and macrophage compartment compared to corresponding controls. In conclusion, we found that activation of STAT6 in the intestinal epithelium predisposes to exacerbated colitis and gut inflammation.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451394"},"PeriodicalIF":4.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816621","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

SHIP-1 Differentially Regulates IgE-Induced IL-10 and Antiviral Responses in Human Monocytes. SHIP-1差异调控ige诱导的人单核细胞IL-10和抗病毒反应

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-12 DOI: 10.1002/eji.202451065

Siva Kumar Solleti, Bailey E Matthews, Jingyi Wu, Regina K Rowe

{"title":"SHIP-1 Differentially Regulates IgE-Induced IL-10 and Antiviral Responses in Human Monocytes.","authors":"Siva Kumar Solleti, Bailey E Matthews, Jingyi Wu, Regina K Rowe","doi":"10.1002/eji.202451065","DOIUrl":"10.1002/eji.202451065","url":null,"abstract":"IgE-mediated stimulation of monocytes regulates multiple cellular functions including cellular maturation, cytokine release, antiviral responses, and T-cell differentiation. Expression of the high-affinity IgE receptor, FcεRI, is closely linked to serum IgE levels and atopic disease. The signaling molecules regulating FcεRI effector functions have been well studied in mast cells and basophils; however, less is known about the signaling and regulatory mechanisms in monocytes. This study sought to identify regulators of IgE-mediated cytokine release in human monocytes. SHIP-1 was identified as a negative regulator of IgE-induced IL-10 production. It was also determined that IgE-mediated stimulation and SHIP-1 inhibition decreased antiviral IP-10 production after liposomal poly(I:C) stimulation, indicating differential regulation by SHIP-1 in IgE-driven and antiviral response pathways. SHIP-1 and NF-κB were activated following IgE-mediated stimulation of monocytes, and NF-κB activation was related to both SHIP-1 and FcεRIα cellular expression levels. To our knowledge, this is the first study to identify a role for SHIP-1 in regulating IgE-mediated and antiviral responses in human monocytes. Given the importance of monocytes in inflammation and immune responses, a better understanding of the signaling and regulatory mechanisms downstream of the FcεRI receptor could lead to new therapeutic targets in allergic disease.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451065"},"PeriodicalIF":4.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816673","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

Dual Activation-Induced Marker Combinations Efficiently Identify and Discern Antigen-Specific and Bystander-Activated Human CD4⁺ T Cells. 双重激活诱导的标记组合有效地识别和辨别抗原特异性和旁观者激活的人CD4+ T细胞。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-11 DOI: 10.1002/eji.202451404

Maria Grazia Ceraolo, Maristella Leccese, Antonino Cassotta, Sara Triolo, Mauro Bombaci, Elena Coluccio, Daniele Prati, Riccardo Ungaro, Sergio Abrignani, Alessandra Bandera, Federica Sallusto, Antonio Lanzavecchia, Samuele Notarbartolo

{"title":"Dual Activation-Induced Marker Combinations Efficiently Identify and Discern Antigen-Specific and Bystander-Activated Human CD4+ T Cells.","authors":"Maria Grazia Ceraolo, Maristella Leccese, Antonino Cassotta, Sara Triolo, Mauro Bombaci, Elena Coluccio, Daniele Prati, Riccardo Ungaro, Sergio Abrignani, Alessandra Bandera, Federica Sallusto, Antonio Lanzavecchia, Samuele Notarbartolo","doi":"10.1002/eji.202451404","DOIUrl":"https://doi.org/10.1002/eji.202451404","url":null,"abstract":"Identifying activated T lymphocytes and differentiating antigen-specific from bystander T cells is crucial for understanding adaptive immune responses. This study investigates the efficacy of activation-induced markers (AIMs) in distinguishing these cell populations. We measured the expression of commonly used AIMs (CD25, CD38, CD40L, CD69, CD137, HLA-DR, ICOS, and OX40) in an in vitro T-cell activation system and evaluated their sensitivity, specificity, and positive predictive value. We demonstrated that individual AIMs, while specific in detecting activated CD4+ T cells, poorly discriminate between antigen-specific and bystander activation, as assessed by a discriminative capacity (DC) score we developed. Our analysis revealed that dual AIM combinations significantly enhanced the ability to distinguish antigen-specific from bystander-activated T cells, achieving DC scores above 90%. These combinations also improved positive predictive value and specificity with a modest reduction in sensitivity. The CD25hi/ICOShi combination emerged as the most efficient, with an average sensitivity of 84.35%, specificity of 99.7%, and DC score of 90.12%. Validation through T-cell cloning and antigen re-stimulation confirmed the robustness of our predictions. This study provides a practical framework for researchers to optimize strategies for identifying and isolating antigen-specific human CD4+ T lymphocytes and studying their phenotype, function, and T-cell receptor repertoire.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451404"},"PeriodicalIF":4.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811689","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

A Switch Protein Adapter for Anti-LILRB4 CAR-T Cells. 抗lilrb4 CAR-T细胞的开关蛋白适配器

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-11 DOI: 10.1002/eji.202451172

Ryan Huang, Heyu Chen, Jingjing Xie, Qi Lou, Lingxiao Tan, Ningyan Zhang, Zhiqiang An, Samuel John, Cheng Cheng Zhang

引用次数: 0

Tumor-Expressed SPPL3 Supports Innate Antitumor Immune Responses. 肿瘤表达的SPPL3支持先天抗肿瘤免疫反应。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-10 DOI: 10.1002/eji.202451129

Tamara Verkerk, Antonius A de Waard, Sofie J I Koomen, Jasper Sanders, Tineke Jorritsma, Anouk T Pappot, Nordin D Zandhuis, Tao Zhang, Manfred Wuhrer, Arie J Hoogendijk, Floris P J van Alphen, Maartje van den Biggelaar, Hannes S J Stockinger, Klaas P J M van Gisbergen, Robbert M Spaapen, S Marieke van Ham

{"title":"Tumor-Expressed SPPL3 Supports Innate Antitumor Immune Responses.","authors":"Tamara Verkerk, Antonius A de Waard, Sofie J I Koomen, Jasper Sanders, Tineke Jorritsma, Anouk T Pappot, Nordin D Zandhuis, Tao Zhang, Manfred Wuhrer, Arie J Hoogendijk, Floris P J van Alphen, Maartje van den Biggelaar, Hannes S J Stockinger, Klaas P J M van Gisbergen, Robbert M Spaapen, S Marieke van Ham","doi":"10.1002/eji.202451129","DOIUrl":"https://doi.org/10.1002/eji.202451129","url":null,"abstract":"The development of an effective antitumor response relies on the synergistic actions of various immune cells that recognize tumor cells via distinct receptors. Tumors, however, often manipulate receptor-ligand interactions to evade recognition by the immune system. Recently, we highlighted the role of neolacto-series glycosphingolipids (nsGSLs), produced by the enzyme β1,3-N-acetylglucosaminyltransferase 5 (B3GNT5), in tumor immune escape. We previously demonstrated that loss of signal peptide peptidase like 3 (SPPL3), an inhibitor of B3GNT5, results in elevated levels of nsGSLs and impairs CD8 T cell activation. The impact of loss of SPPL3 and an elevated nsGSL profile in tumor cells on innate immune recognition remains to be elucidated. This study investigates the antitumor efficacy of neutrophils, NK cells, and γδ T cells on tumor cells lacking SPPL3. Our findings demonstrate that SPPL3-deficient target cells are less susceptible to trogocytosis by neutrophils and killing by NK cells and γδ T cells. Mechanistically, SPPL3 influences trogocytosis and γδ T cell-instigated killing through modulation of nsGSL expression, whereas SPPL3-mediated reduced killing by NK cells is nsGSL-independent. The nsGSL-dependent SPPL3 sensitivity depends on the proximity of surface receptor domains to the cell membrane and the affinity of receptor-ligand interactions as shown with various sets of defined antibodies. Thus, SPPL3 expression by tumor cells alters crosstalk with immune cells through the receptor-ligand interactome thereby driving escape not only from adaptive but also from innate immunity. These data underline the importance of investigating a potential synergism of GSL synthesis inhibitors with current immune cell-activating immunotherapies.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451129"},"PeriodicalIF":4.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798899","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

Issue Information: Eur. J. Immunol. 12'24 发行信息：欧元。[j] .免疫学杂志。12'24 .

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-09 DOI: 10.1002/eji.202470122

引用次数: 0