European Journal of Immunology最新文献

{"title":"Metabolic Reprogramming of Fibroblastic Reticular Cells in Immunity and Tolerance.","authors":"Dejun Kong, Marina WillsonShirkey, Wenji Piao, Long Wu, Shunqun Luo, Allision Kensiski, Jing Zhao, Young Lee, Reza Abdi, Hong Zheng, Jonathan S Bromberg","doi":"10.1002/eji.202451321","DOIUrl":"https://doi.org/10.1002/eji.202451321","url":null,"abstract":"<p><p>Fibroblastic reticular cells (FRCs) are pivotal stromal components that maintain the structure of secondary lymphoid tissues and modulate the immune responses within the lymphoid microenvironment. In response to specific immune or inflammatory stimuli, such as infection or autoimmune triggers, FRCs undergo significant metabolic reprogramming. This process, originally characterized in cancer research, involves the regulation of key metabolic enzymes, pathways, and metabolites, resulting in functional transformations of these cells. Specifically, viruses stimulate FRCs to enhance the tricarboxylic acid cycle, while rheumatoid arthritis and sepsis prompt FRCs to increase oxidative phosphorylation. These changes enable FRCs to adapt their functions, such as proliferation or cytokine secretion, thereby effectively regulating the immune microenvironment to meet the dynamic needs of the immune system. This review provides a comprehensive update on the metabolic reprogramming of FRCs, highlighting how these changes support immune tolerance and response under varied physiological conditions.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451321"},"PeriodicalIF":4.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646277","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}

{"title":"Cytokine Autoantibodies Alter Gene Expression Profiles of Healthy Donors.","authors":"Jakob Hjorth von Stemann, Florian Dubois, Violaine Saint-André, Vincent Bondet, Celine Posseme, Bruno Charbit, Lluis Quintana-Murci, Morten Bagge Hansen, Sisse Rye Ostrowski, Darragh Duffy","doi":"10.1002/eji.202451211","DOIUrl":"https://doi.org/10.1002/eji.202451211","url":null,"abstract":"<p><p>Autoantibodies against cytokines (c-aAb) have been implicated in the pathophysiology of autoimmune diseases, and a variety of infections. In addition, several independent studies have detected elevated titers of c-aAb in the circulation of healthy individuals. To further understand their impact on immune responses, we measured c-aAb against IFN-α, IFN-γ, CSF2, IL-1α, IL-6, and IL-10 in the plasma of 1000 healthy individuals of the Milieu Intérieur (MI) cohort. Focusing on donors above a defined positive cut-off we observed significant age effects for c-aAb against IL-1α, but no major environmental or lifestyle associated factors were identified. Using TruCulture stimulation data from the MI cohort, we observed a strong association between induced IL-1α and c-aAb levels after LPS stimulation. For several other stimuli, c-aAb against IL-1α and IL-10 were associated with decreased or increased proinflammatory gene expression, respectively. Finally, TruCulture assays supplemented with plasma containing high-titer c-aAb showed a strong influence of anti-IFN-α and anti-IL-6 c-aAb on both baseline and induced gene expression. In summary, this study shows a widespread prevalence of anti-cytokine autoantibodies in healthy donors with impacts on diverse immune responses, suggesting a significant contribution of c-aAb to interindividual immune heterogeneity.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451211"},"PeriodicalIF":4.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646207","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}

{"title":"Neural Crest-Derived Mesenchymal Cells Support Thymic Reconstitution After Lethal Irradiation.","authors":"Doris Narki Tetteh, Kana Isono, Mari Hikosaka-Kuniishi, Hidetoshi Yamazaki","doi":"10.1002/eji.202451305","DOIUrl":"https://doi.org/10.1002/eji.202451305","url":null,"abstract":"<p><p>Reconstitution of the thymus is essential for assessing thymic function following injury. However, the currently employed cytoreductive regimes unvaryingly affect the thymic microenvironment, thereby impeding the recovery of T lymphopoiesis. The thymic stroma is composed of epithelial and mesenchymal cells. Thymic mesenchymal cells originate from the Neural crest (NC) and mesoderm and contribute to thymus organogenesis, yet their role in thymic regeneration is unclear. In this study, using transgenic mice expressing NC-specific Cre and Cre-driven DT receptors, we investigated the role of NC-derived mesenchymal cells in thymic regeneration following total body irradiation. We revealed that NC-derived mesenchymal cells have reduced susceptibility to irradiation and induce the upregulation of hematopoietic factors that promote thymus regeneration after irradiation. Additionally, using adult thymic organ culture and renal capsule transplantation, depletion of NC-derived mesenchymal cells resulted in a reduction of DN1-like early T-cell progenitors (ETP) and impaired thymic regeneration. Furthermore, among the numerous factors upregulated by NC-derived mesenchymal cells, Periostin and Flt3L were markedly increased after irradiation and promoted abundance of DN1-like ETPs during thymic reconstitution. Collectively, these findings highlight the importance of NC-derived mesenchymal cells in thymic regeneration.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451305"},"PeriodicalIF":4.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643548","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}

{"title":"The Microbiome Modifies Manifestations of Hemophagocytic Lymphohistiocytosis in Perforin-Deficient Mice.","authors":"Jasmin Mann, Solveig Runge, Christoph Schell, Katja Gräwe, Gudrun Thoulass, Jessica Lao, Sandra Ammann, Sarah Grün, Christoph König, Sarah A Berger, Benedikt Hild, Peter Aichele, Stephan P Rosshart, Stephan Ehl","doi":"10.1002/eji.202451061","DOIUrl":"https://doi.org/10.1002/eji.202451061","url":null,"abstract":"<p><p>Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by inborn errors of cytotoxicity. Patients with biallelic PRF1 null mutations (encoding perforin) usually develop excessive immune cell activation, hypercytokinemia, and life-threatening immunopathology in the first 6 months of life, often without an apparent infectious trigger. In contrast, perforin-deficient (PKO) mice only develop HLH after systemic infection with lymphocytic choriomeningitis virus (LCMV). We hypothesized that restricted microbe-immune cell interactions due to specific pathogen-free (SPF) housing might explain the need for this specific viral trigger in PKO mice. To investigate the influence of a \"wild\" microbiome in PKO mice, we fostered PKO newborns with Wildling microbiota ('PKO-Wildlings') and monitored them for signs of HLH. PKO-Wildlings survived long-term without spontaneous disease. Also, systemic infection with vaccinia virus did not reach the threshold of immune activation required to trigger HLH in PKO-Wildlings. Interestingly, after infection with LCMV, PKO-Wildlings developed an altered HLH pattern. This included lower IFN-γ serum levels along with improved IFN-γ-driven anemia, but more elevated levels of IL-17 and increased liver inflammation compared with PKO-SPF mice. Thus, wild microbiota alone is not sufficient to trigger HLH in PKO mice, but host-microbe interactions shape inflammatory cytokine patterns, thereby influencing manifestations of HLH immunopathology.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451061"},"PeriodicalIF":4.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643549","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}

{"title":"Type I Interferon Drives a Cellular State Inert to TCR-Stimulation and Could Impede Effective T-Cell Differentiation in Cancer.","authors":"Dillon Corvino, Martin Batstone, Brett G M Hughes, Tim Kempchen, Susanna S Ng, Nazhifah Salim, Franziska Schneppenheim, Denise Rommel, Ananthi Kumar, Sally Pearson, Jason Madore, Lambross T Koufariotis, Lisa Maria Steinheuer, Dilan Pathirana, Kevin Thurley, Michael Hölzel, Nicholas Borcherding, Matthias Braun, Tobias Bald","doi":"10.1002/eji.202451371","DOIUrl":"https://doi.org/10.1002/eji.202451371","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) is linked to human papillomavirus (HPV) infection. HPV-positive and HPV-negative HNSCC exhibit distinct molecular and clinical characteristics. Although checkpoint inhibitors have shown efficiency in recurrent/metastatic HNSCC, response variability persists regardless of HPV status. This study aimed to explore the CD8⁺ T-cell landscape in HPV-negative HNSCC.</p><p><strong>Methods: </strong>We performed simultaneous single-cell RNA and TCR sequencing of CD8⁺ tumor-infiltrating lymphocytes (TILs) from treatment-naïve HPV-negative HNSCC patients. Additionally, cells were stimulated ex vivo, which allowed for the tracking of clonal transcriptomic responses.</p><p><strong>Results: </strong>Our analysis identified a subset of CD8⁺ TILs highly enriched for interferon-stimulated genes (ISG). TCR analysis revealed ISG cells are clonally related to a population of granzyme K (GZMK)-expressing cells. However, unlike GZMK cells, which exhibited rapid effector-like phenotypes following stimulation, ISG cells were transcriptionally inert. Additionally, ISG cells showed specific enrichment within tumor and were found across multiple tumor entities.</p><p><strong>Conclusions: </strong>ISG-enriched CD8⁺ TILs are a consistent feature of various tumor entities. These cells are poorly understood but possess characteristics that may impact antitumor immunity. Understanding the unique properties and functionality of ISG cells could offer innovative treatment approaches to improve patient outcomes in HPV-negative HNSCC and other cancer types.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451371"},"PeriodicalIF":4.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613195","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}

{"title":"B Cells With Complementary B Cell Receptors Can Kill Each Other.","authors":"Ramakrishna Prabhu Gopalakrishnan, Marius Sigurdsson Østrøm, Frode Miltzow Skjeldal, Oddmund Bakke, Bjarne Bogen, Peter Csaba Huszthy","doi":"10.1002/eji.202350890","DOIUrl":"https://doi.org/10.1002/eji.202350890","url":null,"abstract":"<p><p>B cells differentiate from hematopoietic stem cells in the bone marrow (BM) and migrate as transitional cells to the spleen where final maturation takes place. Due to the enormous diversity in variable (V) regions of B cell receptors for antigen (BCR), B cells with complementary BCRs are likely to be generated. These could encounter each other in the BM or in secondary lymphoid organs. The outcome of such an event is unknown. To study this issue, we used two strains of gene-modified mice whose B cells display complementary BCRs. B cells of one strain express an idiotype⁺ (Id⁺) BCR while B cells of the other strain display an anti-idiotypic (αId) BCR. In vitro, B cells with complementary BCRs killed each other in a mechanism that required physical binding between BCR V-regions. In contrast, killing was unilateral in vivo: αId B cells with a follicular (FO) B cell phenotype were expanded, while Id⁺ B cells with a marginal zone (MZ) phenotype became deleted. The results show that B cells with complementary BCRs can recognize and regulate each other in vivo. This mechanism should be taken into account in theories for idiotypic regulation of the immune system.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202350890"},"PeriodicalIF":4.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613193","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}

{"title":"Issue Information: Eur. J. Immunol. 11'24","authors":"","doi":"10.1002/eji.202470112","DOIUrl":"https://doi.org/10.1002/eji.202470112","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202470112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640552","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}

{"title":"Cover Story: Eur. J. Immunol. 11'24","authors":"","doi":"10.1002/eji.202470111","DOIUrl":"https://doi.org/10.1002/eji.202470111","url":null,"abstract":"<p>Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI's Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared by flow cytometry and immunology research experts from around the world.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202470111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142641562","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}

{"title":"Impressum","authors":"","doi":"10.1002/eji.202470113","DOIUrl":"10.1002/eji.202470113","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589806","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}

{"title":"Blood transcriptome profiling reveals distinct gene networks induced by mRNA vaccination against COVID-19","authors":"Lennart Riemann,&nbsp;Leonie M. Weskamm,&nbsp;Leonie Mayer,&nbsp;Ivan Odak,&nbsp;Swantje Hammerschmidt,&nbsp;Inga Sandrock,&nbsp;Michaela Friedrichsen,&nbsp;Inga Ravens,&nbsp;Janina Fuss,&nbsp;Gesine Hansen,&nbsp;Marylyn M. Addo,&nbsp;Reinhold Förster","doi":"10.1002/eji.202451236","DOIUrl":"10.1002/eji.202451236","url":null,"abstract":"<p>Messenger RNA (mRNA) vaccines represent a new class of vaccines that has been shown to be highly effective during the COVID-19 pandemic and that holds great potential for other preventative and therapeutic applications. While it is known that the transcriptional activity of various genes is altered following mRNA vaccination, identifying and studying gene networks could reveal important scientific insights that might inform future vaccine designs. In this study, we conducted an in-depth weighted gene correlation network analysis of the blood transcriptome before and 24 h after the second and third vaccination with licensed mRNA vaccines against COVID-19 in humans, following a prime vaccination with either mRNA or ChAdOx1 vaccines. Utilizing this unsupervised gene network analysis approach, we identified distinct modular networks of co-varying genes characterized by either an expressional up- or downregulation in response to vaccination. Downregulated networks were associated with cell metabolic processes and regulation of transcription factors, while upregulated networks were associated with myeloid differentiation, antigen presentation, and antiviral, interferon-driven pathways. Within this interferon-associated network, we identified highly connected hub genes such as <i>STAT2</i> and <i>RIGI</i> and associated upstream transcription factors, potentially playing important regulatory roles in the vaccine-induced immune response. The expression profile of this network significantly correlated with S1-specific IgG levels at the follow-up visit in vaccinated individuals. Those findings could be corroborated in a second, independent cohort of mRNA vaccine recipients. Collectively, results from this modular gene network analysis enhance the understanding of mRNA vaccines from a systems immunology perspective. Influencing specific gene networks could lead to optimized vaccines that elicit augmented vaccine responses.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454215","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}