Immunology最新文献

{"title":"Flagellins as Vaccine Adjuvants and Cancer Immunotherapy: Recent Advances and Future Prospects.","authors":"Asma Talukder, Md Mijanur Rahman, Md Sifat Rahi, Dean L Pountney, Ming Q Wei","doi":"10.1111/imm.70001","DOIUrl":"https://doi.org/10.1111/imm.70001","url":null,"abstract":"<p><p>Flagellin, an essential structural protein of bacterial flagella, has emerged as a potent modulator of both specific and nonspecific immunity, demonstrating significant potential as a vaccine adjuvant and carrier. By inducing the release of pro-inflammatory cytokines like IL-1β, TNF-α, IL-6, IL-8, and IL-12, flagellin activates the innate immune system, enhancing antigen-specific adaptive immune responses mediated by tumour-specific type 1 helper T cells and cytotoxic T cells, thus positioning it as a valuable adjuvant or complementary therapy for various cancers and infectious diseases. This review explores recent strategies, innovations, and clinical applications of flagellin-based immunotherapies, particularly in the context of infectious diseases and cancers. Flagellin from Salmonella typhimurium has been extensively studied as a vaccine adjuvant for diseases like HIV, influenza, dengue, West Nile virus, poultry cholera, and bursal diseases and shows promise in treating lung metastasis, melanoma, colon, and prostate cancers. It has also proven effective against multidrug-resistant bacteria, including Pseudomonas aeruginosa and S. typhimurium. Notably, S. typhimurium flagellin-based vaccines for influenza have progressed to clinical trials. Additionally, flagellins from S. typhi, S. enteritidis, P. aeruginosa, and Escherichia coli are being evaluated as vaccine candidates for plague, malaria, and infections caused by P. aeruginosa and E. coli. In cancer therapy, flagellin-based treatments, especially when combined with tumour antigens, have exhibited the ability to enhance anti-tumour immunity and improve patient outcomes. Other flagellin-based vaccines derived from S. Dublin, S. munchen, and Vibrio vulnificus have been employed in the treatment of prostate, lung, liver, breast, cervical, and colorectal cancers, as well as lymphoma, melanoma, and radiation-induced mucositis. Mobilan, a recombinant non-replicating adenovirus vector expressing Salmonella flagellin, is currently in a phase Ib clinical trial for prostate cancer. Overall, bacterial flagellin treatments are generally safe, well-tolerated, and associated with minimal side effects, making them a promising option for managing infectious diseases and cancers.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257930","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":"Inflammation Perfect Storm: Cancer, Climate and Polarisation.","authors":"Claudio Vieira da Silva","doi":"10.1111/imm.70000","DOIUrl":"https://doi.org/10.1111/imm.70000","url":null,"abstract":"<p><p>Chronic systemic inflammation is increasingly recognised as a central pathological state driving the global burden of non-communicable diseases, most notably cancer, and significantly exacerbated by environmental stressors linked to climate change. This review elucidates the intricate and synergistic relationship between chronic inflammation and cancer, further amplified by the compounding effects of climate change and contemporary sociopolitical polarisation. We examine how biological, environmental and psychosocial factors converge to worsen chronic inflammation and increase cancer risk. Addressing this \"perfect storm\" of converging health threats necessitates a holistic and integrated approach that considers biological vulnerabilities, environmental degradation, the socioeconomic burden of health inequities, and the profound societal impacts of political polarisation to effectively mitigate this escalating global health crisis and promote health equity.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266083","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":"Pannexin-1 Aggravates Inflammatory Bowel Disease via Unbalancing Macrophage Polarisation and Triggering Ferroptosis in Mice.","authors":"Qingfan Zheng, Yunfeng Qiu","doi":"10.1111/imm.13948","DOIUrl":"https://doi.org/10.1111/imm.13948","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is characterised by chronic inflammation in the gastrointestinal tract resulting from dysregulated immune responses to gut microflora. Intestinal macrophages play important roles in the pathogenesis of IBD. The progression of IBD is often associated with increased M1-like macrophages, whereas M2-like macrophages are linked to tissue repair and resolution of inflammation. Ferroptosis in macrophages is potentially involved in IBD pathogenesis. However, the mechanisms underlying the involvement of macrophages and ferroptosis in IBD remain incompletely understood. Here, we established a dextran sodium sulphate (DSS)-induced murine colitis model to recapitulate human IBD. We observed elevated Pannexin-1 (Panx1) expression and an increased M1/M2 macrophage ratio in colonic tissues of DSS-treated mice. Depletion of Panx1 improved DSS-induced colitis via promoting macrophage polarisation into the M2-like phenotype. Furthermore, Panx1 depletion significantly enhanced M2-like macrophage polarisation and moderately inhibited M1-like macrophage polarisation. We further found that depletion of Panx1 reduced ferroptosis in intestinal macrophages from DSS-treated mice, and Glutathione peroxidase 4 (GPX4), a suppressor of ferroptosis, was upregulated in M2-like macrophages rather than M1-like macrophages by Panx1 depletion. In vitro assays showed that depletion of Panx1 inhibited ferroptosis in bone marrow-derived macrophage (BMDM)-derived macrophages. Further analysis showed that Wilms' tumour 1-associating protein (WTAP) inhibited Panx1 expression. Collectively, Panx1 aggravates IBD by shifting macrophage polarisation towards a pro-inflammatory phenotype and enhancing ferroptosis. Our study provides a novel mechanism of IBD pathogenesis and suggests potential therapeutic targets such as Panx1 and macrophage polarisation for IBD.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247720","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":"Cytoplasmic Histone Is a Marker of Pro-Inflammatory CD4⁺ T Cells.","authors":"Bohan Xu, Guanglong Liu, Yifang Peng, Chuxi Chen, Bingsong Li, Tianning Zhu, Nan Huang, Jianyun Zhong, Kang Zhang, Zhizhang Wang","doi":"10.1111/imm.13956","DOIUrl":"https://doi.org/10.1111/imm.13956","url":null,"abstract":"<p><p>Although extranuclear histones have been identified for a long time, their role in lymphocytes, particularly cytoplasmic histones, remains elusive. In this study, we conducted a visual and quantitative analysis of cytoplasmic histones in CD4⁺ T cells and discovered that effector CD4⁺ T cells contain higher levels of cytoplasmic histones compared to naïve T cells. We observed a significant increase in cytoplasmic histones following T cell receptor (TCR) activation, with further elevation during the differentiation of Th1 and Th17 cells. Interestingly, double-stranded RNA (dsRNA) specifically enhanced cytoplasmic histones in Th17, but not in Th1 cells. Additionally, we confirmed that cytoplasmic H2B-positive Th17 cells exhibited increased expression of inflammatory molecules, including pro-inflammatory cytokines. Data are available via ProteomeXchange with identifier PXD063335. Importantly, CD4⁺ T cells from peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) presented elevated levels of cytoplasmic histones. These findings define cytoplasmic histones as markers of proinflammatory CD4⁺ T cells and suggest their potential as biomarkers for autoimmune disease.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225295","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":"Distinct Activation and Functional Features of CD307c⁺ T Lymphocytes in Peripheral Blood as Diagnostic and Prognostic Markers in Breast Cancer.","authors":"Ziqi Xiong, Zhenxue Li, Zhao Guan, Sen Zhou, Yiming Zhao, Ming Zhao, Xiancan Ma, Yiming Gao, Zhonghui Zhang, Pingzhang Wang, Chen Liu","doi":"10.1111/imm.13960","DOIUrl":"https://doi.org/10.1111/imm.13960","url":null,"abstract":"<p><p>This study aims to investigate the expression and role of CD307c in the breast cancer (BC) microenvironment, T lymphocytes of peripheral blood, particularly in BC patients at various stages, and assess its potential as a clinical diagnostic biomarker. Bioinformatics analysis was performed to investigate CD307c expression. As experimental validation, a total of 54 BC patients and 44 healthy controls (HCs) were enrolled. Flow cytometry was used to analyse CD307c expression in CD4⁺ and CD8⁺ T cells, alongside markers of T cell activation and function, such as PD-1, Ki-67, CD25, CD62L, GZMB and GZMK. Ex vivo T cell stimulation with anti-CD3 and anti-CD28 was performed to assess CD307c expression after activation. Statistical analyses, including receiver operating characteristic (ROC) curve analysis, were used to evaluate the diagnostic value of CD307c⁺ T cell subsets. Bioinformatics analysis revealed that CD307c was significantly upregulated in BC tissues compared to adjacent normal tissues, and that CD307c was mainly expressed in lymphocytes, such as B cells, T_regs, CD8⁺ T cells and NKs in the tumour microenvironment. In peripheral blood, CD307c expression was significantly higher in CD4⁺ T cells compared to CD8⁺ T cells. CD307c⁺ T cells exhibited elevated levels of Ki-67, PD-1, CD25 and CD62L, indicating increased activation and potential for immune exhaustion. Additionally, CD307c⁺ CD8⁺ T cells showed higher expression of granzyme B (GZMB) and granzyme K (GZMK), markers of cytotoxicity. In BC patients, CD307c expression was significantly higher in both CD4⁺ and CD8⁺ T cells compared to HCs, and the proportion of CD307c⁺ cells varied across cancer stages. CD307c expression in T lymphocytes is elevated in early-stage BC. CD307c⁺ T cells show enhanced activation, suggesting its potential role as a useful biomarker for early BC diagnosis and a potential therapeutic target.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225296","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":"Neutrophils in the Bone Marrow Express DEC205, Guiding Their Migration to Inflamed Tissues.","authors":"Shiying Jin, Xuan Lei, Sonali Singh, Alexander Enk, Karsten Mahnke","doi":"10.1111/imm.13958","DOIUrl":"https://doi.org/10.1111/imm.13958","url":null,"abstract":"<p><p>The surface molecule DEC205 (CD205) is well-characterised in murine dendritic cells (DCs) as an antigen uptake receptor. However, recent studies have also identified its expression in other leukocytes, including B cells and neutrophils. In B cells, DEC205 functions as an endocytic receptor, similar to its role in DCs. Since neutrophils are not professional antigen-presenting cells, we sought to investigate the functions of DEC205 beyond endocytosis. Analysis of cell surface expression of DEC205 in neutrophils at different maturation stages and anatomical locations revealed its downregulation upon in vitro activation and during tissue infiltration, such as in skin inflammation and thioglycolate-induced peritonitis. In DEC205-deficient (DEC205^-/-) mice, neutrophils exhibited reduced migration in Boyden chamber assays and impaired accumulation in the peritoneum, along with decreased adhesion to extracellular matrix proteins. These findings suggest that, beyond its established role as an antigen uptake receptor in antigen-presenting cells, DEC205 may serve as a marker for early-stage neutrophils with the capacity to migrate and infiltrate tissues.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225297","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":"Loss of ALK3 Ameliorates Acute but Aggravates Chronic Lung Inflammation In Vivo.","authors":"Mathias Hochgerner, Yamei Jiang, Shenfei Sun, Fujing Huang, Leigh M Marsh, Xinhua Lin, Xiaofang Tang","doi":"10.1111/imm.13957","DOIUrl":"https://doi.org/10.1111/imm.13957","url":null,"abstract":"<p><p>ALK3 (BMPR1a) is a type-1 receptor of the TGF-β receptor superfamily. It translates signals mainly from bone morphogenetic proteins, but also from TGF-β1. Previously, we showed that specific deletion of ALK3 in antigen-presenting cells (APCs) led to increased inflammation in the skin. It is unknown whether the regulation of ALK3 in APCs is specific to the skin or generally involved in multiple tissues. Therefore, we investigated the role of ALK3 in APCs in the lung. We used mice with a specific deletion of ALK3 under the CD11c promoter as well as pharmacological blockade of ALK3-signalling with DMH-1 in vivo in Bleomycin- and LPS-induced lung inflammation, as well as follow-up in vitro experiments. Lung inflammation was analysed via histology, flow cytometry and single-cell-RNA-sequencing. Deletion or blockade of ALK3 aggravated Bleomycin-induced and long-term LPS-induced lung inflammation. Interestingly, acute LPS-induced lung inflammation was ameliorated. ALK3 blockade did not reduce recruitment of immune cells to the lung but changed gene expression in neutrophils, downregulating inflammation-associated genes. In vitro, DMH-1 did not directly affect neutrophils but did affect DCs, macrophages and AT-2 cells. The aggravation of longer-lasting lung inflammation matches our previous data from the skin, down to reduced numbers of T_REG. Unexpectedly, that same loss/blockade of ALK3 ameliorates acute lung inflammation. Our results suggest that ALK3 is an important receptor in APCs, enhancing their ability to activate a fast, neutrophilic inflammation as well as to counteract longer-lasting inflammations. Thus, ALK3 has (at least) two different functions at different stages of inflammation. With deeper understanding, ALK3 could be an important target for modulating acute and chronic lung inflammation.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208450","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":"PI3Kγ in Tumour Inflammation: Bridging Immune Response and Cancer Progression-A Mini-Review.","authors":"Anghesom Ghebremedhin, Judith A Varner","doi":"10.1111/imm.13959","DOIUrl":"https://doi.org/10.1111/imm.13959","url":null,"abstract":"<p><p>Phosphatidylinositol 3-kinase gamma (PI3Kγ), a class I PI3K family member, plays a critical role in modulating inflammation and immune responses within the tumour microenvironment. Emerging evidence suggests that PI3Kγ promotes myeloid cell trafficking and transcription, leading to tumour progression and metastasis. This review explores the multifaceted roles of PI3Kγ in tumour-associated inflammation, highlighting its involvement in immune cell polarisation, cytokine production, and the dynamic interaction between tumour cells and the surrounding stromal environment. We also discuss the potential therapeutic implications of targeting PI3Kγ to modulate inflammation and inhibit tumour growth. Given its pivotal role in immune response and tumour progression, PI3Kγ represents a promising target for future cancer therapies to reduce inflammation-driven tumorigenesis.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158424","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":"Delineation of the Human Germinal Centre Immune Landscape Using Multiplex Imaging Analysis.","authors":"Spiros Georgakis, Michail Orfanakis, Craig Fenwick, Cloe Brenna, Simon Burgermeister, Helen Lindsay, Giuliana Xavier de Medeiros, Fernanda Romano Bruno, Susan Pereira Ribeiro, Raphael Gottardo, Giuseppe Pantaleo, Constantinos Petrovas","doi":"10.1111/imm.13955","DOIUrl":"https://doi.org/10.1111/imm.13955","url":null,"abstract":"<p><p>Given the role of follicular immune dynamics, especially the germinal centre, for the development of pathogen-specific antibodies, their in situ characterisation is of great importance. We have developed a multiplex immunofluorescence imaging pipeline that allows the analysis of human follicular adaptive and innate immune cell subsets. Our data revealed the in situ phenotypic heterogeneity and differential localisation of follicular helper CD4 T (T_FH) cell subsets across follicular areas in tonsils and reactive lymph nodes (LNs). Cell clustering analysis identified specific T_FH subsets with differential prevalence between tonsils and LNs. Further, a multiplex RNAscope/protein imaging assay revealed the functional heterogeneity of T_FH cells. No significant differences in follicular innate immune cell densities were found between tonsils and LNs. In conclusion, we present a combinatory experimental approach that provides a comprehensive analysis of human follicular and/or germinal centre immune dynamics and could be used to further understand the pathogenesis of diseases such as HIV and lymphomas.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150371","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":"IFN-λ: Unleashing Its Potential in Disease Therapies From Acute Inflammation Regulation to Cancer Immunotherapy.","authors":"Benfeng Tang, Zhihong Liu, Huabao Xiong, Junfeng Zhang, Jun Dai","doi":"10.1111/imm.13954","DOIUrl":"https://doi.org/10.1111/imm.13954","url":null,"abstract":"<p><p>Type III interferons (IFN-λ), which include IFN-λ1 (or interleukin [IL]-29), IFN-λ2 (IL-28A), IFN-λ3 (IL-28B) and IFN-λ4, exert their effects through a unique receptor complex composed of interferon lambda receptor 1 (IFNLR1) and IL-10 receptor subunit beta (IL-10R2). Studies have highlighted their critical role in modulating immune response, particularly in the context of autoimmune diseases, viral infections and cancer. Unlike type I IFNs, which are broadly expressed, IFN-λ displays a more tissue-specific expression pattern, predominantly acting on epithelial cells and certain immune cell types, such as neutrophils and B cells. This specificity allows IFN-λ to play a pivotal role in mucosal immunity, particularly at barrier sites, such as the respiratory and gastrointestinal tracts. Emerging evidence suggests that IFN-λ has a dual role in both enhancing antiviral immunity and regulating inflammation, thus offering a promising therapeutic strategy for diseases like systemic lupus erythematosus, rheumatoid arthritis, asthma and various cancers. However, the precise mechanisms by which IFN-λ influence immune modulation and disease progression remain an area of active investigation. This review aims to provide an overview of the structure, function and signalling pathways of IFN-λ, exploring their role in immune-related diseases and discussing potential avenues for therapeutic intervention.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150372","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}