Cellular &Molecular Immunology最新文献

{"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":"https://doi.org/10.1038/s41423-025-01276-9","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid droplets restrict phagosome formation in antifungal immunity.","authors":"Wanwei Sun, Han Wu, Guimin Zhao, Qing Shui, Lei Zhang, Xiaoxi Luan, Tian Chen, Feng Liu, Yi Zheng, Wei Zhao, Xiaopeng Qi, Bingyu Liu, Chengjiang Gao","doi":"10.1038/s41423-025-01282-x","DOIUrl":"https://doi.org/10.1038/s41423-025-01282-x","url":null,"abstract":"<p><p>Lipid droplets (LDs) are intracellular organelles that can be induced and interact with phagosomes during the process of pathogen phagocytosis in macrophages. However, the function of LDs in phagocytosis remains elusive. Here, we unveil the role of LDs in modulating phagosome formation via a fungal infection model. Specifically, LD accumulation restricted the degree of phagosome formation and protected macrophages from death. Mechanistically, LD formation competitively consumed the intracellular endoplasmic reticulum membrane and altered RAC1 translocation and GTPase activity, which resulted in limited phagosome formation in macrophages during fungal engulfment. Mice with Hilpda-deficient macrophages were more susceptible to the lethal sequelae of systemic infection with C. albicans. Notably, administration of the ATGL inhibitor atglistatin improved host outcomes in disseminated fungal infections. Taken together, our study elucidates the mechanism by which LDs control phagosome formation to prevent immune cell death and offers a potential drug target for the treatment of C. albicans infections.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802591","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":"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":"https://doi.org/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":""},"PeriodicalIF":21.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: Glycogen synthase kinase 3 controls T-cell exhaustion by regulating NFAT activation.","authors":"Bastien Moës, Christopher E Rudd","doi":"10.1038/s41423-025-01277-8","DOIUrl":"https://doi.org/10.1038/s41423-025-01277-8","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771490","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":"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":"https://doi.org/10.1038/s41423-025-01280-z","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saturated fatty acid-induced neutrophil extracellular traps contribute to exacerbation and biologic therapy resistance in obesity-related psoriasis.","authors":"Yuting Xia, Jiajia Lan, Jing Yang, Shijie Yuan, Xiaorong Xie, Qiuyang Du, Hongyao Du, Wenjia Nie, Biling Jiang, Liang Zhao, Zhen Cai, Xin Zhang, Yan Xiong, Yan Li, Ran He, Juan Tao","doi":"10.1038/s41423-025-01278-7","DOIUrl":"10.1038/s41423-025-01278-7","url":null,"abstract":"<p><p>Psoriasis patients who are obese tend to have serious clinical manifestations and poor responses to various biological agents in most cases. However, the mechanisms by which obesity exacerbates psoriasis remain enigmatic. In this study, we found that the abundance of systemic and localized cutaneous neutrophil extracellular traps (NETs) associated with the obesity-induced aggravation of psoriasis was positively correlated with disease severity and that the inhibition of NETs alleviated psoriatic dermatitis in obese mice. Mechanistically, we found that changes in fatty acid composition in obese subjects resulted in the deposition of saturated fatty acids (SFAs), which promoted the release of NETs via the TLR4-MD2/ROS signaling pathway. We further revealed that NETs potentiate IL-17 inflammation, especially γδT17-mediated immune responses, in obesity-exacerbated psoriasis patients. Moreover, SFAs induced a decreased response to anti-IL17A treatment in psoriasis-like mice, whereas the inhibition of NETs improved the beneficial effects of anti-IL17A in psoriasis-like mice with lipid metabolism disorders. Our findings collectively suggest that SFA-induced NETs play a critical role in the exacerbation of obesity-related psoriasis and provide potential new strategies for the clinical treatment of refractory psoriasis patients with lipid metabolism disorders.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762518","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":"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":""},"PeriodicalIF":21.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Electric power boost\" for CAR-T-cell potency.","authors":"Yadan Bai, Wanlu Liu, Lie Wang, Linrong Lu","doi":"10.1038/s41423-025-01279-6","DOIUrl":"https://doi.org/10.1038/s41423-025-01279-6","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676590","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":"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}