European Journal of Immunology最新文献

Characterization of Human CD8αβ Interaction With Classical and Unconventional MHC Molecules.

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-20 DOI: 10.1002/eji.202451230

Ben de Wet, Robert Alan Simmons, Richard J Suckling, Rita Szoke-Kovacs, Salah Mansour, Marco Lepore, David K Cole, Jakub Jaworski, Alexandra L Chapman, Milos Aleksic

{"title":"Characterization of Human CD8αβ Interaction With Classical and Unconventional MHC Molecules.","authors":"Ben de Wet, Robert Alan Simmons, Richard J Suckling, Rita Szoke-Kovacs, Salah Mansour, Marco Lepore, David K Cole, Jakub Jaworski, Alexandra L Chapman, Milos Aleksic","doi":"10.1002/eji.202451230","DOIUrl":"https://doi.org/10.1002/eji.202451230","url":null,"abstract":"The CD8 co-receptor exists as both an αα homodimer, expressed on subsets of specialized lymphoid cells, and as an αβ heterodimer, which is the canonical co-receptor on cytotoxic T-cells, tuning TCR thymic selection and antigen-reactivity in the periphery. However, the biophysical parameters governing human CD8αβ interactions with classical MHC class I (MHCI) and unconventional MHC-like molecules have not been determined. Using hetero-dimerized Fc-fusions to generate soluble human CD8αβ, we demonstrate similar weak binding affinity to multiple different MHCI alleles compared with CD8αα. We observed that both forms of CD8 bound to certain alleles with stronger affinity than others and found that the affinity of thymically selected TCRs was inversely associated with the affinity of the CD8 co-receptor for the different alleles. We further demonstrated the binding of CD8αα and CD8αβ to the unconventional MHC-like molecule, MHCI-related protein 1, with a similar affinity as for classical MHCI, but no interaction was observed for the other unconventional MHC-like molecules, CD1a, b, c, or d. In summary, this is the first characterization of human CD8αβ binding to MHCI and MHC-like molecules that revealed an intriguing relationship between CD8 binding affinity for different MHCI alleles and the selection of TCRs in the thymus.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451230"},"PeriodicalIF":4.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862655","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

Half-Life Extension of the IgG-Degrading Enzyme (IdeS) Using Fc-Fusion Technology.

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-20 DOI: 10.1002/eji.202451264

Victoria Daventure, Melissa Bou-Jaoudeh, Emna Hannachi, Alejandra Reyes-Ruiz, Amélia Trecco, Sandrine Delignat, Sébastien Lacroix-Desmazes, Claire Deligne

{"title":"Half-Life Extension of the IgG-Degrading Enzyme (IdeS) Using Fc-Fusion Technology.","authors":"Victoria Daventure, Melissa Bou-Jaoudeh, Emna Hannachi, Alejandra Reyes-Ruiz, Amélia Trecco, Sandrine Delignat, Sébastien Lacroix-Desmazes, Claire Deligne","doi":"10.1002/eji.202451264","DOIUrl":"https://doi.org/10.1002/eji.202451264","url":null,"abstract":"Imlifidase (IdeS) is a bacterial protease that hydrolyzes human IgG in their hinge region, decreasing their half-life and abrogating their Fc-mediated properties. It is now successfully used in therapy to prevent graft rejection during kidney transplants and is being clinically evaluated in several IgG-mediated autoimmune diseases. IdeS short half-life however limits its clinical use, particularly in the case of chronic diseases that would request repeated administrations. Here, we developed IdeS-Fc fusion proteins as a divalent homodimer (IdeS-Fcdiv) or a monovalent heterodimer (IdeS-Fcmonov), in order to extend the IgG-depleting action of IdeS over time. Both IdeS-Fc efficiently separated monoclonal and polyclonal human IgG into F(ab')2 and Fc fragments, although with slower kinetics than their native counterpart. IdeS-Fcmonov exhibited a seven-fold half-life extension in vivo as compared with IdeS, and a significantly better residual cleavage of human IgG at later time points after injection. Our results provide proof of concept for the use of an IdeS with extended IgG-hydrolyzing functions in vivo that could rapidly translate to the clinic.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451264"},"PeriodicalIF":4.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862698","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

The Efficiency of Brain-Derived Neurotrophic Factor Secretion by mRNA-Electroporated Regulatory T Cells Is Highly Impacted by Their Activation Status.

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-19 DOI: 10.1002/eji.202451005

Jasper Van den Bos, Ibo Janssens, Morgane Vermeulen, Amber Dams, Hans De Reu, Stefanie Peeters, Carole Faghel, Yousra El Ouaamari, Inez Wens, Nathalie Cools

{"title":"The Efficiency of Brain-Derived Neurotrophic Factor Secretion by mRNA-Electroporated Regulatory T Cells Is Highly Impacted by Their Activation Status.","authors":"Jasper Van den Bos, Ibo Janssens, Morgane Vermeulen, Amber Dams, Hans De Reu, Stefanie Peeters, Carole Faghel, Yousra El Ouaamari, Inez Wens, Nathalie Cools","doi":"10.1002/eji.202451005","DOIUrl":"https://doi.org/10.1002/eji.202451005","url":null,"abstract":"Genetic engineering of regulatory T cells (Tregs) presents a promising avenue for advancing immunotherapeutic strategies, particularly in autoimmune diseases and transplantation. This study explores the modification of Tregs via mRNA electroporation, investigating the influence of T-cell activation status on transfection efficiency, phenotype, and functionality. For this CD45RA+ Tregs were isolated, expanded, and modified to overexpress brain-derived neurotrophic factor (BDNF). Kinetics of BDNF expression and secretion were explored. Treg activation state was assessed by checking the expression of activation markers CD69, CD71, and CD137. Our findings show that only activated Tregs secrete BDNF post-genetic engineering, even though both activated and resting Tregs express BDNF intracellularly. Notably, the mTOR pathway and CD137 are implicated in the regulation of protein secretion in activated Tregs, indicating a complex interplay of signalling pathways. This study contributes to understanding the mechanisms governing protein expression and secretion in engineered Tregs, offering insights for optimizing cell-based therapies and advancing immune regulation strategies.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451005"},"PeriodicalIF":4.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862699","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

BAFF Blockade Attenuates B Cell MALT Formation in Conditional Nlrc5-Deficient Mice With Helicobacter felis Infection.

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-17 DOI: 10.1002/eji.202451355

Dongmei Tong, Yuqi He, Shambel Araya Haile, Zoe Lee, Lena H M Le, Jack Emery, Georgie Wray-McCan, Michelle Chonwerawong, Dana J Philpott, Paul J Hertzog, Pascal Schneider, Richard L Ferrero, Le Ying

{"title":"BAFF Blockade Attenuates B Cell MALT Formation in Conditional Nlrc5-Deficient Mice With Helicobacter felis Infection.","authors":"Dongmei Tong, Yuqi He, Shambel Araya Haile, Zoe Lee, Lena H M Le, Jack Emery, Georgie Wray-McCan, Michelle Chonwerawong, Dana J Philpott, Paul J Hertzog, Pascal Schneider, Richard L Ferrero, Le Ying","doi":"10.1002/eji.202451355","DOIUrl":"https://doi.org/10.1002/eji.202451355","url":null,"abstract":"Helicobacter infection is a key cause of gastric B cell mucosa-associated lymphoid tissue (MALT) lymphoma. This study examined the role of B cell-activating factor (BAFF), a major driver of B cell proliferation and many B cell disorders, in this malignancy using a model in which conditional knockout mice for NOD-like receptor family CARD domain-containing 5 (Nlrc5) are infected with Helicobacter felis. Gastric BAFF production was significantly increased in H. felis-infected Nlrc5mø-KO mice compared to wild-type. Blocking BAFF signalling, before or after the onset of Helicobacter-induced gastritis, significantly reduced MALT development, with fewer gastric B cell follicles and reduced gland hyperplasia. BAFF blockade also reshaped the immune cell landscape in the stomach, resulting in fewer CD4+ T cells, Tregs, macrophages and dendritic cells. Using a cell culture model, we identified the protein-coding BAFF transcripts that are upregulated in NLRC5-deficient macrophages stimulated with either H. felis or the NLRC5 agonist, lipopolysaccharide. Among the upregulated variants, TNFSF13B (BAFF)-206 acts as a transcription factor and is reported to enhance BAFF production in autoimmune diseases and cancer. Altogether, these findings implicate the NLRC5-BAFF signalling axis in Helicobacter-induced B cell MALT lymphoma, highlighting BAFF inhibition as a potential therapeutic approach.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451355"},"PeriodicalIF":4.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833398","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.

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

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

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.

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.

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

Guidelines for preparation and flow cytometry analysis of human nonlymphoid tissue DC. 人类非淋巴组织 DC 的制备和流式细胞术分析指南。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-12 DOI: 10.1002/eji.202250325

Diana Dudziak, Lukas Heger, William W Agace, Joyce Bakker, Tanja D de Gruijl, Regine J Dress, Charles-Antoine Dutertre, Thomas M Fenton, Marieke F Fransen, Florent Ginhoux, Oded Heyman, Yael Horev, Florian Hornsteiner, Vinitha Kandiah, Paz Kles, Ruth Lubin, Gabriel Mizraji, Anastasia Prokopi, Or Saar, Sieghart Sopper, Patrizia Stoitzner, Helen Strandt, Martina M Sykora, Elisa C Toffoli, Christoph H Tripp, Kim van Pul, Rieneke van de Ven, Asaf Wilensky, Simon Yona, Claudia Zelle-Rieser

{"title":"Guidelines for preparation and flow cytometry analysis of human nonlymphoid tissue DC.","authors":"Diana Dudziak, Lukas Heger, William W Agace, Joyce Bakker, Tanja D de Gruijl, Regine J Dress, Charles-Antoine Dutertre, Thomas M Fenton, Marieke F Fransen, Florent Ginhoux, Oded Heyman, Yael Horev, Florian Hornsteiner, Vinitha Kandiah, Paz Kles, Ruth Lubin, Gabriel Mizraji, Anastasia Prokopi, Or Saar, Sieghart Sopper, Patrizia Stoitzner, Helen Strandt, Martina M Sykora, Elisa C Toffoli, Christoph H Tripp, Kim van Pul, Rieneke van de Ven, Asaf Wilensky, Simon Yona, Claudia Zelle-Rieser","doi":"10.1002/eji.202250325","DOIUrl":"https://doi.org/10.1002/eji.202250325","url":null,"abstract":"This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs, and various nonlymphoid tissues. Within this article, detailed protocols are presented that allow for the generation of single-cell suspensions from human nonlymphoid tissues including lung, skin, gingiva, intestine as well as from tumors and tumor-draining lymph nodes with a subsequent analysis of dendritic cells by flow cytometry. Further, prepared single-cell suspensions can be subjected to other applications including cellular enrichment procedures, RNA sequencing, functional assays, etc. While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer-reviewed by leading experts and approved by all co-authors, making it an essential resource for basic and clinical DC immunologists.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2250325"},"PeriodicalIF":4.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816629","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