Cellular &Molecular Immunology最新文献

{"title":"Reply to 'Comment on: Glycogen synthase kinase 3 controls T-cell exhaustion by regulating NFAT activation'.","authors":"Yubing Fu, Wen-Hsien Liu","doi":"10.1038/s41423-025-01280-z","DOIUrl":"10.1038/s41423-025-01280-z","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":"559-562"},"PeriodicalIF":21.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the brain: microglia-like cells regulate peripheral neuronal soma size.","authors":"Siling Du, Jonathan Kipnis","doi":"10.1038/s41423-025-01276-9","DOIUrl":"10.1038/s41423-025-01276-9","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":"466-467"},"PeriodicalIF":21.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor cells that resist neutrophil anticancer cytotoxicity acquire a prometastatic and innate immune escape phenotype.","authors":"Jagoda Agnieszka Szlachetko, Francisca Hofmann-Vega, Bettina Budeus, Lara-Jasmin Schröder, Claudia Alexandra Dumitru, Mathias Schmidt, Eric Deuss, Sebastian Vollmer, Eva-Maria Hanschmann, Maike Busch, Jan Kehrmann, Stephan Lang, Nicole Dünker, Timon Hussain, Sven Brandau","doi":"10.1038/s41423-025-01283-w","DOIUrl":"10.1038/s41423-025-01283-w","url":null,"abstract":"<p><p>In the tumor host, neutrophils may exhibit protumor or antitumor activity. It is hypothesized that in response to host-derived or therapy-induced factors, neutrophils adopt diverse functional states to ultimately execute these differential functions. Here, we provide an alternative scenario in which the response of an individual tumor cell population determines the overall protumor versus antitumor outcome of neutrophil‒tumor interactions. Experimentally, we show that human neutrophils, which are sequentially stimulated with bacteria and secreted factors from tumor cells, kill a certain proportion of tumor target cells. However, the majority of the tumor cells remained resistant to this neutrophil-mediated killing and underwent a functional, phenotypic and transcriptomic switch that was reminiscent of partial epithelial‒to-mesenchymal transition. This cell biological switch was associated with physical escape from NK-mediated killing and resulted in enhanced metastasis to the lymph nodes in a preclinical orthotopic mouse model. Mechanistically, we identified the antimicrobial neutrophil granule proteins neutrophil elastase (NE) and matrix metalloprotease-9 (MMP-9) as the molecular mediators of this functional switch. We validated these data in patients with head and neck cancer and identified bacterially colonized intratumoral niches that were enriched for mesenchymal tumor cells and neutrophils expressing NE and MMP-9. Our data reveal the parallel execution of tumor cytotoxic and prometastatic activity by activated neutrophils and identify NE and MMP-9 as mediators of lymph node metastasis. The identified mechanism explains the functional dichotomy of tumor-associated neutrophils at the level of the tumor target cell response and has implications for superinfected cancers and the dysbiotic tumor microenvironment.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":"527-540"},"PeriodicalIF":21.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol homeostasis and lipid raft dynamics at the basis of tumor-induced immune dysfunction in chronic lymphocytic leukemia.","authors":"Chaja F Jacobs, Fleur S Peters, Elena Camerini, Gaspard Cretenet, Joanne Rietveld, Bauke V Schomakers, Michel van Weeghel, Nico Hahn, Sanne G S Verberk, Jan Van den Bossche, Mirjam Langeveld, Fleur Kleijwegt, Eric Eldering, Noam Zelcer, Arnon P Kater, Helga Simon-Molas","doi":"10.1038/s41423-025-01262-1","DOIUrl":"10.1038/s41423-025-01262-1","url":null,"abstract":"<p><p>Autologous T-cell therapies show limited efficacy in chronic lymphocytic leukemia (CLL), where acquired immune dysfunction prevails. In CLL, disturbed mitochondrial metabolism has been linked to defective T-cell activation and proliferation. Recent research suggests that lipid metabolism regulates mitochondrial function and differentiation in T cells, yet its role in CLL remains unexplored. This comprehensive study compares T-cell lipid metabolism in CLL patients and healthy donors, revealing critical dependence on exogenous cholesterol for human T-cell expansion following TCR-mediated activation. Using multi-omics and functional assays, we found that T cells present in viably frozen samples of patients with CLL (CLL T cells) showed impaired adaptation to cholesterol deprivation and inadequate upregulation of key lipid metabolism transcription factors. CLL T cells exhibited altered lipid storage, with increased triacylglycerols and decreased cholesterol, and inefficient fatty acid oxidation (FAO). Functional consequences of reduced FAO in T cells were studied using samples from patients with inherent FAO disorders. Reduced FAO was associated with lower T-cell activation but did not affect proliferation. This implicates low cholesterol levels as a primary factor limiting T-cell proliferation in CLL. CLL T cells displayed fewer and less clustered lipid rafts, potentially explaining the impaired immune synapse formation observed in these patients. Our findings highlight significant disruptions in lipid metabolism as drivers of functional deficiencies in CLL T cells, underscoring the pivotal role of cholesterol in T-cell proliferation. This study suggests that modulating cholesterol metabolism could enhance T-cell function in CLL, presenting novel immunotherapeutic approaches to improve outcome in this challenging disease.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":"485-500"},"PeriodicalIF":21.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPNMB disrupts SNARE complex assembly to maintain bacterial proliferation within macrophages.","authors":"Zhenzhen Yan, Jinghong Han, Zihao Mi, Zhenzhen Wang, Yixuan Fu, Chuan Wang, Ningning Dang, Hong Liu, Furen Zhang","doi":"10.1038/s41423-025-01272-z","DOIUrl":"10.1038/s41423-025-01272-z","url":null,"abstract":"<p><p>Xenophagy plays a crucial role in restraining the growth of intracellular bacteria in macrophages. However, the machinery governing autophagosome‒lysosome fusion during bacterial infection remains incompletely understood. Here, we utilize leprosy, an ideal model for exploring the interactions between host defense mechanisms and bacterial infection. We highlight the glycoprotein nonmetastatic melanoma protein B (GPNMB), which is highly expressed in macrophages from lepromatous leprosy (L-Lep) patients and interferes with xenophagy during bacterial infection. Upon infection, GPNMB interacts with autophagosomal-localized STX17, leading to a reduced N-glycosylation level at N296 of GPNMB. This modification promotes the degradation of SNAP29, thus preventing the assembly of the STX17-SNAP29-VAMP8 SNARE complex. Consequently, the fusion of autophagosomes with lysosomes is disrupted, resulting in inhibited cellular autophagic flux. In addition to Mycobacterium leprae, GPNMB deficiency impairs the proliferation of various intracellular bacteria in human macrophages, suggesting a universal role of GPNMB in intracellular bacterial infection. Furthermore, compared with their counterparts, Gpnmb^fl/fl Lyz2-Cre mice presented decreased Mycobacterium marinum amplification. Overall, our study reveals a previously unrecognized role of GPNMB in host antibacterial defense and provides insights into its regulatory mechanism in SNARE complex assembly.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":"512-526"},"PeriodicalIF":21.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The intrinsic expression of NLRP3 in Th17 cells promotes their protumor activity and conversion into Tregs.","authors":"Théo Accogli, Christophe Hibos, Lylou Milian, Mannon Geindreau, Corentin Richard, Etienne Humblin, Romain Mary, Sandy Chevrier, Elise Jacquin, Antoine Bernard, Fanny Chalmin, Catherine Paul, Berhard Ryffel, Lionel Apetoh, Romain Boidot, Mélanie Bruchard, François Ghiringhelli, Frédérique Vegran","doi":"10.1038/s41423-025-01281-y","DOIUrl":"10.1038/s41423-025-01281-y","url":null,"abstract":"<p><p>Th17 cells can perform either regulatory or inflammatory functions depending on the cytokine microenvironment. These plastic cells can transdifferentiate into Tregs during inflammation resolution, in allogenic heart transplantation models, or in cancer through mechanisms that remain poorly understood. Here, we demonstrated that NLRP3 expression in Th17 cells is essential for maintaining their immunosuppressive functions through an inflammasome-independent mechanism. In the absence of NLRP3, Th17 cells produce more inflammatory cytokines (IFNγ, Granzyme B, TNFα) and exhibit reduced immunosuppressive activity toward CD8+ cells. Moreover, the capacity of NLRP3-deficient Th17 cells to transdifferentiate into Treg-like cells is lost. Mechanistically, NLRP3 in Th17 cells interacts with the TGF-β receptor, enabling SMAD3 phosphorylation and thereby facilitating the acquisition of immunosuppressive functions. Consequently, the absence of NLRP3 expression in Th17 cells from tumor-bearing mice enhances CD8 + T-cell effectiveness, ultimately inhibiting tumor growth.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":"541-556"},"PeriodicalIF":21.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"γδ T cells as sensors of ectopically expressed intracellular proteins","authors":"Dieter Kabelitz,&nbsp;Jaydeep Bhat","doi":"10.1038/s41423-025-01269-8","DOIUrl":"10.1038/s41423-025-01269-8","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 4","pages":"456-458"},"PeriodicalIF":21.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-025-01269-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NLRP3 inflammasome in neuroinflammation and central nervous system diseases","authors":"Wen Xu,&nbsp;Yi Huang,&nbsp;Rongbin Zhou","doi":"10.1038/s41423-025-01275-w","DOIUrl":"10.1038/s41423-025-01275-w","url":null,"abstract":"Neuroinflammation plays an important role in the pathogenesis of various central nervous system (CNS) diseases. The NLRP3 inflammasome is an important intracellular multiprotein complex composed of the innate immune receptor NLRP3, the adaptor protein ASC, and the protease caspase-1. The activation of the NLRP3 inflammasome can induce pyroptosis and the release of the proinflammatory cytokines IL-1β and IL-18, thus playing a central role in immune and inflammatory responses. Recent studies have revealed that the NLRP3 inflammasome is activated in the brain to induce neuroinflammation, leading to further neuronal damage and functional impairment, and contributes to the pathological process of various neurological diseases, such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and stroke. In this review, we summarize the important role of the NLRP3 inflammasome in the pathogenesis of neuroinflammation and the pathological course of CNS diseases and discuss potential approaches to target the NLRP3 inflammasome for the treatment of CNS diseases.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 4","pages":"341-355"},"PeriodicalIF":21.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-025-01275-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fueling defense: PPARα enhances macrophage inflammatory responses","authors":"Marten A. Hoeksema","doi":"10.1038/s41423-025-01265-y","DOIUrl":"10.1038/s41423-025-01265-y","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 4","pages":"461-462"},"PeriodicalIF":21.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the origin of neutrophils","authors":"Leo Koenderman,&nbsp;Kiki Tesselaar,&nbsp;Nienke Vrisekoop","doi":"10.1038/s41423-025-01270-1","DOIUrl":"10.1038/s41423-025-01270-1","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 4","pages":"459-460"},"PeriodicalIF":21.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}