Cellular &Molecular Immunology最新文献

{"title":"Author Correction: Genetic and epigenetic influences on the loss of tolerance in autoimmunity","authors":"Peng Zhang, Qianjin Lu","doi":"10.1038/s41423-024-01201-6","DOIUrl":"10.1038/s41423-024-01201-6","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 9","pages":"1082-1082"},"PeriodicalIF":21.8,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01201-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792080","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":"Targeting the glucocorticoid receptor-CCR8 axis mediated bone marrow T cell sequestration enhances infiltration of anti-tumor T cells in intracranial cancers","authors":"Jia Zhang, Yuzhu Shi, Xiaotong Xue, Wenqing Bu, Yanan Li, Tingting Yang, Lijuan Cao, Jiankai Fang, Peishan Li, Yongjing Chen, Zhen Li, Changshun Shao, Yufang Shi","doi":"10.1038/s41423-024-01202-5","DOIUrl":"10.1038/s41423-024-01202-5","url":null,"abstract":"Brain tumors such as glioblastomas are resistant to immune checkpoint blockade therapy, largely due to limited T cell infiltration in the tumors. Here, we show that mice bearing intracranial tumors exhibit systemic immunosuppression and T cell sequestration in bone marrow, leading to reduced T cell infiltration in brain tumors. Elevated plasma corticosterone drives the T cell sequestration via glucocorticoid receptors in tumor-bearing mice. Immunosuppression mediated by glucocorticoid-induced T cell dynamics and the subsequent tumor growth promotion can be abrogated by adrenalectomy, the administration of glucocorticoid activation inhibitors or glucocorticoid receptor antagonists, and in mice with T cell-specific deletion of glucocorticoid receptor. CCR8 expression in T cells is increased in tumor-bearing mice in a glucocorticoid receptor-dependent manner. Additionally, chemokines CCL1 and CCL8, the ligands for CCR8, are highly expressed in bone marrow immune cells in tumor-bearing mice to recruit T cells. These findings suggested that brain tumor-induced glucocorticoid surge and CCR8 upregulation in T cells lead to T cell sequestration in bone marrow, impairing the anti-tumor immune response. Targeting the glucocorticoid receptor-CCR8 axis may offer a promising immunotherapeutic approach for the treatment of intracranial tumors.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 10","pages":"1145-1157"},"PeriodicalIF":21.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751217","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":"GPR34 senses demyelination to promote neuroinflammation and pathologies","authors":"Bolong Lin, Yubo Zhou, Zonghui Huang, Ming Ma, Minghui Qi, Zhongjun Jiang, Guoyang Li, Yueli Xu, Jiaxian Yan, Di Wang, Xiaqiong Wang, Wei Jiang, Rongbin Zhou","doi":"10.1038/s41423-024-01204-3","DOIUrl":"10.1038/s41423-024-01204-3","url":null,"abstract":"Sterile neuroinflammation is a major driver of multiple neurological diseases. Myelin debris can act as an inflammatory stimulus to promote inflammation and pathologies, but the mechanism is poorly understood. Here, we showed that lysophosphatidylserine (LysoPS)-GPR34 axis played a critical role in microglia-mediated myelin debris sensing and the subsequent neuroinflammation. Myelin debris-induced microglia activation and proinflammatory cytokine expression relied on its lipid component LysoPS. Both myelin debris and LysoPS promoted microglia activation and the production of proinflammatory cytokines via GPR34 and its downstream PI3K-AKT and ERK signaling. In vivo, reducing the content of LysoPS in myelin or inhibition of GPR34 with genetic or pharmacological approaches reduced neuroinflammation and pathologies in the mouse models of multiple sclerosis and stroke. Thus, our results identify GPR34 as a key receptor to sense demyelination and CNS damage and promote neuroinflammation, and suggest it as a potential therapeutic target for demyelination-associated diseases.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 10","pages":"1131-1144"},"PeriodicalIF":21.8,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726972","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":"Orchestration of antiviral responses within the infected central nervous system","authors":"Andreas Pavlou, Felix Mulenge, Olivia Luise Gern, Lena Mareike Busker, Elisabeth Greimel, Inken Waltl, Ulrich Kalinke","doi":"10.1038/s41423-024-01181-7","DOIUrl":"10.1038/s41423-024-01181-7","url":null,"abstract":"Many newly emerging and re-emerging viruses have neuroinvasive potential, underscoring viral encephalitis as a global research priority. Upon entry of the virus into the CNS, severe neurological life-threatening conditions may manifest that are associated with high morbidity and mortality. The currently available therapeutic arsenal against viral encephalitis is rather limited, emphasizing the need to better understand the conditions of local antiviral immunity within the infected CNS. In this review, we discuss new insights into the pathophysiology of viral encephalitis, with a focus on myeloid cells and CD8+ T cells, which critically contribute to protection against viral CNS infection. By illuminating the prerequisites of myeloid and T cell activation, discussing new discoveries regarding their transcriptional signatures, and dissecting the mechanisms of their recruitment to sites of viral replication within the CNS, we aim to further delineate the complexity of antiviral responses within the infected CNS. Moreover, we summarize the current knowledge in the field of virus infection and neurodegeneration and discuss the potential links of some neurotropic viruses with certain pathological hallmarks observed in neurodegeneration.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 9","pages":"943-958"},"PeriodicalIF":21.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01181-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141598744","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":"Extramedullary neutrophil progenitors: Quo Vadis?","authors":"Leo Koenderman, Nienke Vrisekoop","doi":"10.1038/s41423-024-01191-5","DOIUrl":"10.1038/s41423-024-01191-5","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 8","pages":"932-934"},"PeriodicalIF":21.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558176","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":"Targeting pro-fibrotic macrophages with bioactive self-assembly peptides to retard kidney fibrosis – know thyself","authors":"Steven O’Reilly","doi":"10.1038/s41423-024-01194-2","DOIUrl":"10.1038/s41423-024-01194-2","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 8","pages":"935-937"},"PeriodicalIF":21.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558177","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":"Food restriction heals darkness-related second brain inflammation","authors":"Vinicius Kannen","doi":"10.1038/s41423-024-01196-0","DOIUrl":"10.1038/s41423-024-01196-0","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 8","pages":"938-940"},"PeriodicalIF":21.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537605","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":"Tissue-resident memory T cells break tolerance to renal autoantigens and orchestrate immune-mediated nephritis","authors":"Frederic Arnold, Laurence Kupferschmid, Philipp Weissenborn, Lukas Heldmann, Jonas F. Hummel, Paulina Zareba,  Sagar, Manuel Rogg, Christoph Schell, Yakup Tanriver","doi":"10.1038/s41423-024-01197-z","DOIUrl":"10.1038/s41423-024-01197-z","url":null,"abstract":"Immune-mediated nephritis is a leading cause of acute kidney injury and chronic kidney disease. While the role of B cells and antibodies has been extensively investigated in the past, the advent of immune-checkpoint inhibitors has led to a reappraisal of the role of T cells in renal immunology. However, it remains elusive how T cells with specificity for renal autoantigens are activated and participate in immune-mediated nephritis. Here, we followed the fate and function of pathogen-activated autoreactive CD8 T cells that are specific for a renal autoantigen. We demonstrate that recently activated splenic CD8 T cells developed a hybrid phenotype in the context of renal autoantigen cross-presentation, combining hallmarks of activation and T cell dysfunction. While circulating memory T cells rapidly disappeared, tissue-resident memory T cells emerged and persisted within the kidney, orchestrating immune-mediated nephritis. Notably, T cells infiltrating kidneys of patients with interstitial nephritis also expressed key markers of tissue residency. This study unveils how a tissue-specific immune response can dissociate from its systemic counterpart driving a compartmentalized immune response in the kidneys of mice and man. Consequently, targeting tissue-resident memory T cells emerges as a promising strategy to control immune-mediated kidney disease.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 9","pages":"1066-1081"},"PeriodicalIF":21.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01197-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497262","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":"Lipid droplet accumulation mediates macrophage survival and Treg recruitment via the CCL20/CCR6 axis in human hepatocellular carcinoma","authors":"Yongchun Wang, Weibai Chen, Shuang Qiao, Hao Zou, Xing-juan Yu, Yanyan Yang, Zhixiong Li, Junfeng Wang, Min-shan Chen, Jing Xu, Limin Zheng","doi":"10.1038/s41423-024-01199-x","DOIUrl":"10.1038/s41423-024-01199-x","url":null,"abstract":"Metabolic changes play a crucial role in determining the status and function of macrophages, but how lipid reprogramming in macrophages contributes to tumor progression is not yet fully understood. Here, we investigated the phenotype, contribution, and regulatory mechanisms of lipid droplet (LD)-laden macrophages (LLMs) in hepatocellular carcinoma (HCC). Enriched LLMs were found in tumor tissues and were associated with disease progression in HCC patients. The LLMs displayed immunosuppressive phenotypes (with extensive expression of TREM2, PD-L1, CD206, and CD163) and attenuated the antitumor activities of CD8+ T cells. Mechanistically, tumor-induced reshuffling of cellular lipids and TNFα-mediated uptake of tumoral fatty acids contribute to the generation of triglycerides and LDs in macrophages. LDs prolong LLM survival and promote CCL20 secretion, which further recruits CCR6+ Tregs to HCC tissue. Inhibiting LLM formation by targeting DGAT1 and DGAT2, which catalyze the synthesis of triglycerides, significantly reduced Treg recruitment, and delayed tumor growth in a mouse hepatic tumor model. Our results reveal the suppressive phenotypes and mechanisms of LLM enrichment in HCC and suggest the therapeutic potential of targeting LLMs for HCC patients.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 10","pages":"1120-1130"},"PeriodicalIF":21.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466539","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":"BAG6 restricts pancreatic cancer progression by suppressing the release of IL33-presenting extracellular vesicles and the activation of mast cells","authors":"Bilal Alashkar Alhamwe, Viviane Ponath, Fahd Alhamdan, Bastian Dörsam, Clara Landwehr, Manuel Linder, Kim Pauck, Sarah Miethe, Holger Garn, Florian Finkernagel, Anna Brichkina, Matthias Lauth, Dinesh Kumar Tiwari, Malte Buchholz, Daniel Bachurski, Sabrina Elmshäuser, Andrea Nist, Thorsten Stiewe, Lisa Pogge von Strandmann, Witold Szymański, Vanessa Beutgen, Johannes Graumann, Julia Teply-Szymanski, Corinna Keber, Carsten Denkert, Ralf Jacob, Christian Preußer, Elke Pogge von Strandmann","doi":"10.1038/s41423-024-01195-1","DOIUrl":"10.1038/s41423-024-01195-1","url":null,"abstract":"Recent studies reveal a critical role of tumor cell-released extracellular vesicles (EVs) in pancreatic cancer (PC) progression. However, driver genes that direct EV function, the EV-recipient cells, and their cellular response to EV uptake remain to be identified. Therefore, we studied the role of Bcl-2-associated-anthanogene 6 (BAG6), a regulator of EV biogenesis for cancer progression. We used a Cre recombinase/LoxP-based reporter system in combination with single-cell RNA sequencing to monitor in vivo EV uptake and tumor microenvironment (TME) changes in mouse models for pancreatic ductal adenocarcinoma (PDAC) in a Bag6 pro- or deficient background. In vivo data were validated using mouse and human organoids and patient samples. Our data demonstrated that Bag6-deficient subcutaneous and orthotopic PDAC tumors accelerated tumor growth dependent on EV release. Mechanistically, this was attributed to mast cell (MC) activation via EV-associated IL33. Activated MCs promoted tumor cell proliferation and altered the composition of the TME affecting fibroblast polarization and immune cell infiltration. Tumor cell proliferation and fibroblast polarization were mediated via the MC secretome containing high levels of PDGF and CD73. Patients with high BAG6 gene expression and high protein plasma level have a longer overall survival indicating clinical relevance. The current study revealed a so far unknown tumor-suppressing activity of BAG6 in PDAC. Bag6-deficiency allowed the release of EV-associated IL33 which modulate the TME via MC activation promoting aggressive tumor growth. MC depletion using imatinib diminished tumor growth providing a scientific rationale to consider imatinib for patients stratified with low BAG6 expression and high MC infiltration.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 8","pages":"918-931"},"PeriodicalIF":21.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466515","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}