Immunology最新文献

{"title":"Characterising the Transcriptomic Response to Interferon and Infection in European Domestic Ferret Respiratory Tissues Using Long-Read RNA Sequencing.","authors":"Rubaiyea Farrukee, Jessie J-Y Chang, Jianshu Zhang, James B Barnes, Shu Xin Zhang, Sher Maine Tan, Patrick C Reading, Lachlan J M Coin","doi":"10.1111/imm.70042","DOIUrl":"https://doi.org/10.1111/imm.70042","url":null,"abstract":"<p><p>The European domestic ferret (Mustela putorius furo) is considered the gold standard small animal model for studying human and avian influenza virus infections. However, experimental characterisation of the transcriptomic response to interferon (IFN) stimulation and/or influenza virus infection has been limited, particularly in defining the induction of interferon-stimulated genes (ISGs), with most being computationally predicted. In this study, we present a comprehensive transcriptome-wide assessment of the ferret transcriptome following IFN-α treatment of a ferret lung (FRL) cell line, as well as in nasal turbinates from influenza A virus (IAV)-infected ferrets using long-read RNA sequencing. We have identified a panel of ferret genes orthologous to human ISGs that are upregulated both in response to IFN-α stimulation in vitro and IAV infection in vivo. We have also identified novel IFN-stimulated genes and transcripts. Furthermore, we observed elongation of the poly(A) tails of genes in the ribosome and Coronavirus Disease-19 pathways in response to IFN-α treatment in vitro, suggesting a relationship between poly(A) elongation and the antiviral responses of the host. These results illuminate the dynamics of the transcriptional innate immune response of the domestic ferret and provide an important resource for better utilising ferrets as a small animal model to study influenza virus infections.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244547","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":"Antibody Polyreactivity: A Challenger of Immune Paradigms.","authors":"Anastas D Pashov, Jordan D Dimitrov","doi":"10.1111/imm.70048","DOIUrl":"https://doi.org/10.1111/imm.70048","url":null,"abstract":"<p><p>Polyreactivity refers to the ability of antibodies to bind multiple unrelated antigens, encompassing polyspecificity and promiscuity. Here, we discuss the diverse molecular mechanisms underlying polyreactivity, including conformational dynamics, sequence- and structural characteristics of antigen-binding sites. The importance of polyreactive antibodies in immune defence and immune homeostasis is highlighted as well as their potential pathological consequences. Polyreactivity is seen as a continuum rather than a discrete property so that ultimately all antibodies possess some degree of polyreactivity. The challenges in defining antibody specificity are examined, and a shift towards quantitative thinking in antibody research is suggested. This would foster the adoption of novel methodologies to study complex antibody-antigen interactions at a systems level. Finally, the deeper understanding of polyreactivity's potential implications for the current antibody paradigm is critically evaluated.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225243","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":"Mechanism of Tumour-Associated Macrophage-Derived Exosomes in Chemo-Sensitivity of Laryngeal Cancer by Regulating Aerobic Glycolysis via WTAP/GLUT-1.","authors":"Xingmei Luo, Guodong Li, Yu Chen, Tongli Li","doi":"10.1111/imm.70039","DOIUrl":"https://doi.org/10.1111/imm.70039","url":null,"abstract":"<p><p>Laryngeal cancer (LC) is a condition characterised by cancerous cell development in laryngeal tissues. This article focuses on the mechanism of tumour-associated macrophage-derived exosomes (TAM-Exos) in LC chemosensitivity by mediating Wilms' tumour 1-associating protein (WTAP)/glucose transporter-1 (GLUT-1). Human peripheral blood mononuclear cells (PBMCs) were cultured in vitro. Macrophage colony-stimulating factor (M-CSF) was used to induce the differentiation of PBMCs into human peripheral blood macrophages (M0), which were further induced into tumour-associated macrophages-educated macrophages (TAMEMs^C-h) by 20% human recombinant protein cocktail and transfected with sh-WTAP. TU686 cells were treated with TAMEMs^C-h derived Exos, cisplatin (DDP), 2-deoxyglucose, and small-interfering-GLUT-1, with TAMEMs^C-h morphology and phenotype assessed. Finally, nude mice were treated with DDP and Exos for in vivo verification. TAMEMs^C-h-derived Exos promoted aerobic glycolysis and reduced LC cell sensitivity to DDP. TAMEMs^C-h-derived Exos increased glucose uptake, lactic acid, lactate dehydrogenase, and adenosine triphosphate levels, facilitated aerobic glycolysis, viability, and invasion, and decreased apoptotic rate by mediating WTAP, thus reducing DDP sensitivity in TU686 cells. But the effect of TAM-Exos was reversed in response to aerobic glycolysis suppression or GLUT-1 knockdown. TAM-Exos carrying WTAP increased GLUT-1 N6-methyladenosine (m6A) modification and GLUT-1 messenger RNA (mRNA) stability, hence boosting GLUT-1 expression. TAM-Exos boosted aerobic glycolysis by mediating WTAP/GLUT-1, thus decreasing DDP sensitivity and enhancing tumour growth. TAM-Exos promoted the m6A modification of GLUT-1 through WTAP, and improved GLUT-1 mRNA stability and expression, thereby promoting aerobic glycolysis and reducing the chemo-sensitivity of LC.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212475","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":"Exhaustion-Resistant CD8⁺ T Cells in Ankylosing Spondylitis: A Proposed Three-Axis Model.","authors":"Xuhong Zhang, Lu Jia, Xueni Lin, Lamei Zhou","doi":"10.1111/imm.70044","DOIUrl":"https://doi.org/10.1111/imm.70044","url":null,"abstract":"<p><p>Ankylosing spondylitis (AS) is a chronic immune-mediated disease marked by sustained joint inflammation and aberrant bone remodelling. Although chronic antigen exposure usually enforces terminal exhaustion, emerging evidence indicates that a subset of CD8⁺ T cells in AS evades canonical exhaustion programmes while expressing programmed cell death protein 1 (PD-1). These exhaustion-resistant cells retain effector function and likely contribute to persistent tissue inflammation and structural damage. In this review, we dissect the cellular and molecular basis of exhaustion resistance in AS CD8⁺ T cells and focus on the convergence of intermittent T cell receptor (TCR) stimulation, metabolic adaptation that preserves mitochondrial fitness, and co-stimulatory inputs from interleukin-15 (IL-15) and CD28. We propose an integrated three-axis model governing CD8⁺ T cell fate and functional persistence in the AS context shaped by human leukocyte antigen-B27 (HLA-B27) and the gut-joint axis. Clarifying these mechanisms refines current views of T cell dysfunction in chronic inflammation and highlights therapeutic strategies aimed at reprogramming pathogenic immunity in AS.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212491","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":"β-Glucan Protects Against Sepsis-Induced Kupffer Cell Loss by Inhibiting Pyroptosis and Promoting Self-Renewal.","authors":"Joseph Adams, Tingting Li, Peilin Zhu, Chloe Garbe, Fei Tu, Jared Casteel, Valentin Yakubenko, David L Williams, Chuanfu Li, Xiaohui Wang","doi":"10.1111/imm.70043","DOIUrl":"https://doi.org/10.1111/imm.70043","url":null,"abstract":"<p><p>Sepsis is a life-threatening condition characterised by a dysregulated host response to infection, resulting in systemic inflammation, immune dysfunction, and multi-organ failure. Kupffer cells (KCs), the largest population of tissue-resident macrophages in the body, are essential for pathogen clearance, endotoxin detoxification, and maintaining hepatic immune homeostasis during sepsis. However, sepsis induces substantial KC depletion, contributing to increased bacterial burden and mortality. In this study, we demonstrate that β-glucan treatment effectively protects against sepsis-induced KC loss and reduces circulating bacterial load. Mechanistically, β-glucan attenuates KC death by suppressing NLRP3 and gasdermin D (GSDMD)-mediated pyroptosis triggered by bacterial infections. Notably, we identify a previously unrecognised function of β-glucan in markedly enhancing KC self-renewal during sepsis through downregulation of the transcriptional repressors c-Maf and MafB, which are known to inhibit macrophage proliferation. This discovery reveals a novel mechanism of hepatic macrophage regeneration and supports β-glucan as a promising immunomodulatory therapy to preserve liver immune integrity, enhancing antibacterial defence, and reducing the risk of secondary infections in immunocompromised septic hosts.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212558","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":"Challenge Specific Modulation of Responses to Adjuvant-Induced Innate Immune Memory.","authors":"Samuel T Pasco, Itziar Martín-Ruiz, Sarai Araujo-Aris, Diego Barriales, Janire Castelo, Leire Egia-Mendikute, Monika Gonzalez, Jose Ezequiel Martin, Elena Molina, Maitane Mugica, Ainhoa Palacios, Iratxe Seoane, Naiara Gutiez, Estibaliz Atondo, Eneko Santos Fernández, Maddi Oyanguren, Borja Jimenez-Lasheras, Ainize Peña-Cearra, Ana M Aransay, Asis Palazon, Aize Pellón, Leticia Abecia, Hector Rodriguez, Natalia Elguezabal, Juan Anguita","doi":"10.1111/imm.70047","DOIUrl":"https://doi.org/10.1111/imm.70047","url":null,"abstract":"<p><p>Understanding the innate immune memory induced by adjuvants provides an opportunity to improve vaccine efficacy by inducing nonspecific secondary responses alongside the intended adaptive defence against the target antigen. To understand the consequences of adjuvant-induced immune training, we treated mice with commercially available Sigma Adjuvant System (SAS) and performed functional assays of bone marrow-derived innate immune cells, assessed its functional consequences in vivo, determined the resulting haematopoietic stem and progenitor cell (HSPC) phenotypes, and extensively analyzed the HSPC transcriptome. SAS induced temporal shifts in HSPC frequencies, alterations in the circulating blood profile, and lowered proinflammatory output by macrophages. SAS-induced training caused disparate outcomes in models of inflammation and acute infection. Further, SAS enhanced antibody responses after primary immunisation, that were profoundly altered upon a secondary dose. Integrated transcriptional analysis revealed shifts in HSPCs defined by altered transcription factor activity and lineage-specific shifts in metabolic, epigenetic, myeloid, and kinase genes, resulting in enhanced antimicrobial neutrophil responsiveness and revealing regulators of central training. Together, these results contribute to the understanding of the plasticity and limitations of innate immune training.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206469","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":"Isogenic Immune Cells From T-iPSCs for Studying T Cell-Macrophage Interactions.","authors":"Ludwig Englmeier, Alexandra Lucaciu","doi":"10.1111/imm.70041","DOIUrl":"https://doi.org/10.1111/imm.70041","url":null,"abstract":"","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199176","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":"γδ T Cell Infiltration Predicts the Prognosis of Lumbar Disc Herniation.","authors":"Huijuan Wan, Bing Liu, Qian Zhang, Qiang Hua, Chunping Chen, Meixiang Lan, Xiaoying Wen, Wanbin Cai, Yongjun Chen, Ning Zhang, Qing Liang, Kejia Wang","doi":"10.1111/imm.70040","DOIUrl":"https://doi.org/10.1111/imm.70040","url":null,"abstract":"<p><p>Lumbar disc herniation (LDH) is a common degenerative spinal disorder traditionally attributed to mechanical compression. However, growing evidence suggests that the immune system plays a crucial role in its pathogenesis. The role of alterations in the T cell receptor (TCR) clonal repertoire in LDH and their correlation with neurological recovery was investigated in this study. Immunohistochemical analysis was performed to assess T cell infiltration in nucleus pulposus tissue from patients with LDH, while TCR immune repertoire sequencing was conducted on peripheral blood mononuclear cells to examine TCR clonal diversity and gene rearrangement patterns. The results revealed a significant reduction in TCR clonal diversity in patients with LDH, with selective expansion of specific V, J, and VDJ gene segments indicating abnormal clonal proliferation of certain T cell subsets. Furthermore, local CD3⁺ (r = 0.5193; p = 0.0039) and TCRγδ⁺ (r = 0.6137; p < 0.001) T cell densities were positively correlated with Japanese Orthopaedic Association (JOA) scores, whereas white blood cell (r = -0.3861; p = 0.0351) and neutrophil counts (r = -0.4243; p = 0.0194) were negatively correlated with JOA scores. This study highlights the immunological characteristics of TCR repertoire alterations in LDH and suggests that TCR clonal profiling could serve as a potential biomarker for personalized immunotherapy.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137385","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":"Correction to \"A Novel Polymersome Nanocarrier Promotes Anti-Tumour Immunity by Improved Priming of CD8⁺ T Cells\".","authors":"","doi":"10.1111/imm.70005","DOIUrl":"https://doi.org/10.1111/imm.70005","url":null,"abstract":"","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130144","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":"Mitochondrial Activity Regulates Human T Helper 17 Differentiation and Function.","authors":"Xinlai Chen, Theodoros Ioannis Papadimitriou, Anne H G van Essen, Britt van Brunschot, Monique M Helsen, Annet Sloetjes, Elly L Vitters, Werner J H Koopman, Peter M van der Kraan, Arjan P M van Caam, Marije I Koenders","doi":"10.1111/imm.70037","DOIUrl":"https://doi.org/10.1111/imm.70037","url":null,"abstract":"<p><p>Immunometabolism plays a pivotal role in T cell fate decisions, yet its specific contribution to human Th17 differentiation remains incompletely understood. Th17 cells, a subset of CD4⁺ T cells, are central to autoimmune pathogenesis through their secretion of pro-inflammatory cytokines. Elucidating the metabolic drivers of Th17 differentiation may reveal novel therapeutic targets. We investigated the role of mitochondrial activity in Th17 differentiation using an in vitro model with naïve human CD4⁺ T cells. Single-cell metabolic profiling and functional assays were used to characterise metabolic changes during differentiation. Th17 cells exhibited a hyperpolarised mitochondrial membrane potential (ΔΨ) compared to non-Th17 cells. Hyperpolarised ΔΨ cells displayed increased metabolic activity and enhanced differentiation capacity. Metabolic profiling at 48 h revealed an early reliance on glycolysis, followed by a shift toward increased dependence on oxidative phosphorylation (OXPHOS) by 96 h. Gene expression analysis indicated early upregulation of TEFM, a mitochondrial transcription regulator, at 48 h. By 96 h, ΔΨ hyperpolarised cells exhibited a downregulation of DRP1 and MFN2, genes responsible for mitochondrial fission and fusion. Functionally, ΔΨ hyperpolarised cells expressed elevated activation markers (CD69, CD25) but also showed increased exhaustion markers (TIGIT, PD-1), indicating a link between high metabolic activity and exhaustion. Additionally, these cells triggered weaker NF-κB and AP-1 signalling and secreted lower levels of effector molecules (IFN-γ, Granzyme B) than ΔΨ depolarised cells. In conclusion, mitochondrial activity critically shapes Th17 differentiation. Although hyperpolarised ΔΨ cells exhibit greater activation, they are more prone to exhaustion and reduced effector function. These findings offer insights into Th17 metabolic regulation and its therapeutic potential in autoimmune diseases.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075238","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}