European Journal of Immunology最新文献_第2页

SHIP-1 Differentially Regulates IgE-Induced IL-10 and Antiviral Responses in Human Monocytes.

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.

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.

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.

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

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

High Extracellular K⁺ Skews T-Cell Differentiation Towards Tumour Promoting Th2 and T_reg Subsets.

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-09 DOI: 10.1002/eji.202451440

Brandon Han Siang Wong, Zhi Sheng Poh, James Tan Chia Wei, Kottaiswamy Amuthavalli, Ying Swan Ho, Shuwen Chen, Shi Ya Mak, Xuezhi Bi, Richard D Webster, Vishalkumar G Shelat, K George Chandy, Navin Kumar Verma

{"title":"High Extracellular K+ Skews T-Cell Differentiation Towards Tumour Promoting Th2 and Treg Subsets.","authors":"Brandon Han Siang Wong, Zhi Sheng Poh, James Tan Chia Wei, Kottaiswamy Amuthavalli, Ying Swan Ho, Shuwen Chen, Shi Ya Mak, Xuezhi Bi, Richard D Webster, Vishalkumar G Shelat, K George Chandy, Navin Kumar Verma","doi":"10.1002/eji.202451440","DOIUrl":"https://doi.org/10.1002/eji.202451440","url":null,"abstract":"Potassium ions (K+) released from dying necrotic tumour cells accumulate in the tumour microenvironment (TME) and increase the local K+ concentration to 50 mM (high-[K+]e). Here, we demonstrate that high-[K+]e decreases expression of the T-cell receptor subunits CD3ε and CD3ζ and co-stimulatory receptor CD28 and thereby dysregulates intracellular signal transduction cascades. High-[K+]e also alters the metabolic profiles of T-cells, limiting the metabolism of glucose and glutamine, consistent with functional exhaustion. These changes skew T-cell differentiation, favouring Th2 and iTreg subsets that promote tumour growth while restricting antitumour Th1 and Th17 subsets. Similar phenotypes were noted in T-cells present within the necrosis-prone core versus the outer zones of hepatocellular carcinoma (HCC)/colorectal carcinoma (CRC) tumours as analysed by GeoMx digital spatial profiling and flow-cytometry. Our results thus expand the understanding of the contribution of high-[K+]e to the immunosuppressive milieu in the TME.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451440"},"PeriodicalIF":4.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798898","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

Cover Story: Eur. J. Immunol. 12'24

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-09 DOI: 10.1002/eji.202470121

引用次数: 0

Impressum 印象深刻

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-09 DOI: 10.1002/eji.202470123

引用次数: 0

Probing TCR Specificity Using Artificial In Vivo Diversification of CDR3 Regions.

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-02 DOI: 10.1002/eji.202451434

Orlando B Giorgetti, Annette Haas-Assenbaum, Thomas Boehm

{"title":"Probing TCR Specificity Using Artificial In Vivo Diversification of CDR3 Regions.","authors":"Orlando B Giorgetti, Annette Haas-Assenbaum, Thomas Boehm","doi":"10.1002/eji.202451434","DOIUrl":"https://doi.org/10.1002/eji.202451434","url":null,"abstract":"The T-cell receptor sequences expressed on cells recognizing a specific peptide in the context of a given MHC molecule can be explored for common features that might explain their antigen specificity. However, despite the development of numerous experimental and bioinformatic strategies, the specificity problem remains unresolved. To address the need for additional experimental paradigms, we report here on an in vivo experimental strategy designed to artificially diversify a transgenic TCR by CRISPR/Cas9-mediated mutagenesis of Tcra and Tcrb chain genes. In this system, an initially monoclonal repertoire of known specificity is converted into an oligoclonal pool of TCRs of altered antigen reactivity. Tracking the fate of individual clonotypes during the intrathymic differentiation process illuminates the strong selective pressures that shape the repertoire of naïve T cells. Sequence analyses of the artificially diversified repertoires identify key amino acid residues in the CDR3 regions required for antigen recognition, indicating that artificial diversification of well-characterized TCR transgene sequences helps to reduce the complexities of learning the rules of antigen recognition.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451434"},"PeriodicalIF":4.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764914","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

Function and Spatial Organization of Tumor-Invasive Human γδ T Cells-What Do We Know?

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-02 DOI: 10.1002/eji.202451075

Kilian Wistuba-Hamprecht, Hans-Heinrich Oberg, Daniela Wesch

{"title":"Function and Spatial Organization of Tumor-Invasive Human γδ T Cells-What Do We Know?","authors":"Kilian Wistuba-Hamprecht, Hans-Heinrich Oberg, Daniela Wesch","doi":"10.1002/eji.202451075","DOIUrl":"https://doi.org/10.1002/eji.202451075","url":null,"abstract":"Human gammadelta (γδ) T cells not only infiltrate or reside in healthy tissues but also enter solid cancers. A large body of evidence suggests that γδ T cells can exert potent anti-tumor effects, although conflicting or unfavorable effects have been reported in some cancer entities. Infiltration patterns are key to understanding the complexity of the tumor microenvironment (TME) and its interplay with γδ T cells. The limited data available describe different γδ T cell subsets that are located in different areas around and within tumors. Tumor-infiltrating γδ lymphocytes (γδ TIL) exert cytotoxicity, for example, via the CD95- or TRAIL-axis, produce high amounts of granzymes, and after their activation, tumor necrosis factor (TNF)-α or IFN-γ and express immune checkpoint receptors. Under certain conditions, γδ T cell subsets can express low amounts of IL-17 and seem to contribute to immune regulation/suppression. A polarization of γδ T cells can be influenced by the TME. Inflammatory cytokines, growth factors, or tumor promoters can suppress γδ T cell functionality or even push them toward tumor promotion. To avoid this and to exploit the unique features of γδ T cell-mediated anti-cancer and immune-orchestrating capabilities in future immune therapy approaches, a growing body of preclinical but also clinical studies can be observed.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451075"},"PeriodicalIF":4.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764913","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