European Journal of Immunology最新文献_第3页

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

IL1R2 Acts as a Negative Regulator of Monocyte Recruitment During Inflammation.

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-11-28 DOI: 10.1002/eji.202451468

Adeline Cros, Elodie Segura

引用次数: 0

Distinct Requirements for CD4⁺ T Cell Help for Immune Responses Induced by mRNA and Adenovirus-Vector SARS-CoV-2 Vaccines. mRNA 和腺病毒载体 SARS-CoV-2 疫苗诱导的免疫应答对 CD4+ T 细胞帮助的不同要求

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-11-27 DOI: 10.1002/eji.202451142

Lyn Yong, Claire Hutchings, Eleanor Barnes, Paul Klenerman, Nicholas M Provine

{"title":"Distinct Requirements for CD4+ T Cell Help for Immune Responses Induced by mRNA and Adenovirus-Vector SARS-CoV-2 Vaccines.","authors":"Lyn Yong, Claire Hutchings, Eleanor Barnes, Paul Klenerman, Nicholas M Provine","doi":"10.1002/eji.202451142","DOIUrl":"https://doi.org/10.1002/eji.202451142","url":null,"abstract":"CD4+ T cells have been established as central orchestrators of cellular and humoral immune responses to infection or vaccination. However, the need for CD4+ T cell help to generate primary CD8+ T cell responses is variable depending on the infectious agent or vaccine and yet consistently required for the recall of CD8+ T cell memory responses or antibody responses. Given the deployment of new vaccine platforms such as nucleoside-modified mRNA vaccines, we sought to elucidate the requirement for CD4+ T cell help in the induction of cellular and antibody responses to mRNA and adenovirus (Ad)-vectored vaccines against SARS-CoV-2. Using antibody-mediated depletion of CD4+ T cells in a mouse immunization model, we observed that CD4+ T cell help was dispensable for both primary and secondary CD8+ T cell responses to the BNT162b2 and mRNA-1273 mRNA vaccines but required for the AZD1222 Ad-vectored vaccine. Nonetheless, CD4+ T cell help was needed by both mRNA and Ad-vectored vaccine platforms for the generation of antibodies, demonstrating the centrality of CD4+ T cells in vaccine-induced protective immunity against SARS-CoV-2. Ultimately, this highlights the shared and distinct regulation of humoral and cellular responses induced by these vaccine platforms.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451142"},"PeriodicalIF":4.5,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737901","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

Differential Characteristics on TCR Embedding Landscape Among Immune Checkpoint Blockade Responders Versus Non-Responders Against Non-Small Cell Lung Carcinoma. 免疫检查点阻断剂治疗非小细胞肺癌的应答者与非应答者在 TCR 嵌入景观上的差异特征

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-11-27 DOI: 10.1002/eji.202451374

Peiling Tsou, Chang-Jiun Wu

引用次数: 0

Crafting an MSCA PhD Masterpiece: Guiding Students on the Verge of Discovery. 打造 MSCA 博士杰作：指导学生走向发现的边缘。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-11-26 DOI: 10.1002/eji.202451659

Lisa Dratva, Alice Driessen, Igor Filippov, Stéphane Guillaume, Lisa Hoenicke, Jean-Christophe Lone

引用次数: 0

Memory Phenotype Tfh Cells Develop Without Overt Infection and Support Germinal Center Formation and B Cell Responses to Viral Infection. 记忆表型 Tfh 细胞在没有明显感染的情况下发育，支持生殖中心的形成和 B 细胞对病毒感染的反应。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-11-20 DOI: 10.1002/eji.202451291

Alistair L J Symonds, Zabreen Busharat, Mengmeng Du, Tizong Miao, Suling Li, Xiujuan Hou, Ping Wang

{"title":"Memory Phenotype Tfh Cells Develop Without Overt Infection and Support Germinal Center Formation and B Cell Responses to Viral Infection.","authors":"Alistair L J Symonds, Zabreen Busharat, Mengmeng Du, Tizong Miao, Suling Li, Xiujuan Hou, Ping Wang","doi":"10.1002/eji.202451291","DOIUrl":"https://doi.org/10.1002/eji.202451291","url":null,"abstract":"Pathogen-induced memory Tfh cells are important to maintain high-affinity antibodies against pathogens. We have now discovered Tfh cells with a similar memory phenotype (MP) that develop in pathogen-free conditions. These MP Tfh cells are similar to pathogen-induced memory Tfh in both phenotype and function. They express FR4 and Egr2, which are both found in pathogen-induced memory Tfh cells. FR4+Egr2+ CD4 MP cells express genes involved in the development of Tfh cells and homeostatic proliferation, as well as key metabolic pathways discovered in pathogen-induced memory Tfh cells. MP Tfh cells can support B cell-mediated IgG production in vitro and induce germinal center formation and anti-viral antibodies in response to virus infection. These mouse MP Tfh cells share a similar phenotype to human circulating Tfh cells that are increased in Sjögren's syndrome patients. Although Foxp3-positive circulating T follicular regulatory (Tfr) cells are normal, a proportion of circulating Tfh cells from patients express increased levels of T-bet, which is associated with high levels of inflammatory pathology. Thus, although they do not require overt infection for their development, MP Tfh cells are important for protective immune responses, and dysregulated MP Tfh responses may play a role in autoimmunity.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451291"},"PeriodicalIF":4.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680027","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

Metabolic Reprogramming of Fibroblastic Reticular Cells in Immunity and Tolerance. 免疫和耐受中成纤维网细胞的代谢重编程

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-11-18 DOI: 10.1002/eji.202451321

Dejun Kong, Marina WillsonShirkey, Wenji Piao, Long Wu, Shunqun Luo, Allision Kensiski, Jing Zhao, Young Lee, Reza Abdi, Hong Zheng, Jonathan S Bromberg

{"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":"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.","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}

引用次数: 0

Cytokine Autoantibodies Alter Gene Expression Profiles of Healthy Donors. 细胞因子自身抗体改变了健康捐献者的基因表达谱。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-11-17 DOI: 10.1002/eji.202451211

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

{"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":"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.","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}

引用次数: 0

Neural Crest-Derived Mesenchymal Cells Support Thymic Reconstitution After Lethal Irradiation. 神经冠衍生间充质细胞支持致命照射后胸腺的重建

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-11-16 DOI: 10.1002/eji.202451305

Doris Narki Tetteh, Kana Isono, Mari Hikosaka-Kuniishi, Hidetoshi Yamazaki

{"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":"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.","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}

引用次数: 0

The Microbiome Modifies Manifestations of Hemophagocytic Lymphohistiocytosis in Perforin-Deficient Mice. 微生物组改变穿孔素缺陷小鼠嗜血细胞淋巴组织细胞增多症的表现形式

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-11-16 DOI: 10.1002/eji.202451061

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

{"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":"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.","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}

引用次数: 0