Cellular &Molecular Immunology最新文献_第2页

No more LAGging behind PD-1: uncovering the unique role of LAG-3 in T-cell exhaustion. PD-1背后不再有LAG：揭示LAG-3在T细胞衰竭中的独特作用。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-21 DOI: 10.1038/s41423-024-01227-w

Yunju Jo, Hyung-Seung Jin, Yoon Park

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CD30 influences germinal center B-cell dynamics and the expansion of IgG1-switched B cells. CD30 影响生殖中心 B 细胞的动态和 IgG1 开关 B 细胞的扩增。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-17 DOI: 10.1038/s41423-024-01219-w

Yan Wang, Ursula Rambold, Petra Fiedler, Tea Babushku, Claas L Tapken, Kai P Hoefig, Thomas P Hofer, Heiko Adler, Ali Önder Yildirim, Lothar J Strobl, Ursula Zimber-Strobl

{"title":"CD30 influences germinal center B-cell dynamics and the expansion of IgG1-switched B cells.","authors":"Yan Wang, Ursula Rambold, Petra Fiedler, Tea Babushku, Claas L Tapken, Kai P Hoefig, Thomas P Hofer, Heiko Adler, Ali Önder Yildirim, Lothar J Strobl, Ursula Zimber-Strobl","doi":"10.1038/s41423-024-01219-w","DOIUrl":"https://doi.org/10.1038/s41423-024-01219-w","url":null,"abstract":"Initially, identified as a Hodgkin lymphoma marker, CD30 was subsequently detected on a subset of human B cells within and around germinal centers (GCs). While CD30 expression is typically restricted to a few B cells, expansion of CD30-expressing B cells occurs in certain immune disorders and during viral infections. The role of CD30 in B cells remains largely unclear. To address this gap in knowledge, we established a conditional CD30-knockin mouse strain. In these mice, B-cell-specific CD30 expression led to a normal B-cell phenotype in young mice, but most aged mice exhibited significant expansion of B cells, T cells and myeloid cells and increased percentages of GC B cells and IgG1-switched cells. This may be driven by the expansion of CD4+ senescence-associated T cells and T follicular helper cells, which partially express CD30-L (CD153) and may stimulate CD30-expressing B cells. Inducing CD30 expression in antigen-activated B cells accelerates the GC reaction and augments plasma cell differentiation, possibly through the posttranscriptional upregulation of CXCR4. Furthermore, CD30 expression in GC B cells promoted the expansion of IgG1-switched cells, which displayed either a GC or memory-like B-cell phenotype, with abnormally high IgG1 levels compared with those in controls. These findings shed light on the role of CD30 signaling in GC B cells and suggest that elevated CD30+ B-cell numbers lead to pathological lymphocyte activation and proliferation.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459284","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}

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Immunotherapy for glioblastoma: current state, challenges, and future perspectives. 胶质母细胞瘤的免疫疗法：现状、挑战和未来展望。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-15 DOI: 10.1038/s41423-024-01226-x

Yang Liu, Fei Zhou, Heba Ali, Justin D Lathia, Peiwen Chen

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Macrophage diversity in cancer dissemination and metastasis 癌症传播和转移中的巨噬细胞多样性

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-14 DOI: 10.1038/s41423-024-01216-z

Alberto Mantovani, Federica Marchesi, Diletta Di Mitri, Cecilia Garlanda

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Regulation of CD8+ T cells by lipid metabolism in cancer progression 癌症进展过程中脂质代谢对 CD8+ T 细胞的调控。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-14 DOI: 10.1038/s41423-024-01224-z

Yong Tang, Ziqing Chen, Qianying Zuo, Yibin Kang

{"title":"Regulation of CD8+ T cells by lipid metabolism in cancer progression","authors":"Yong Tang, Ziqing Chen, Qianying Zuo, Yibin Kang","doi":"10.1038/s41423-024-01224-z","DOIUrl":"10.1038/s41423-024-01224-z","url":null,"abstract":"Dysregulation of lipid metabolism is a key characteristic of the tumor microenvironment, where tumor cells utilize lipids for proliferation, survival, metastasis, and evasion of immune surveillance. Lipid metabolism has become a critical regulator of CD8+ T-cell-mediated antitumor immunity, with excess lipids in the tumor microenvironment impeding CD8+ T-cell activities. Considering the limited efficacy of immunotherapy in many solid tumors, targeting lipid metabolism to enhance CD8+ T-cell effector functions could significantly improve immunotherapy outcomes. In this review, we examine recent findings on how lipid metabolic processes, including lipid uptake, synthesis, and oxidation, regulate CD8+ T cells within tumors. We also assessed the impact of different lipids on CD8+ T-cell-mediated antitumor immunity, with a particular focus on how lipid metabolism affects mitochondrial function in tumor-infiltrating CD8+ T cells. Furthermore, as cancer is a systemic disease, we examined systemic factors linking lipid metabolism to CD8+ T-cell effector function. Finally, we summarize current therapeutic approaches that target lipid metabolism to increase antitumor immunity and enhance immunotherapy. Understanding the molecular and functional interplay between lipid metabolism and CD8+ T cells offers promising therapeutic opportunities for cancer treatment.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 11","pages":"1215-1230"},"PeriodicalIF":21.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01224-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459288","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}

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Silencing of SIRPα enhances the antitumor efficacy of CAR-M in solid tumors 沉默 SIRPα 可增强 CAR-M 在实体瘤中的抗肿瘤疗效。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-08 DOI: 10.1038/s41423-024-01220-3

Han Zhang, Yi Huo, Wenjing Zheng, Peng Li, Hui Li, Lingling Zhang, Longqi Sa, Yang He, Zihao Zhao, Changhong Shi, Lequn Shan, Angang Yang, Tao Wang

{"title":"Silencing of SIRPα enhances the antitumor efficacy of CAR-M in solid tumors","authors":"Han Zhang, Yi Huo, Wenjing Zheng, Peng Li, Hui Li, Lingling Zhang, Longqi Sa, Yang He, Zihao Zhao, Changhong Shi, Lequn Shan, Angang Yang, Tao Wang","doi":"10.1038/s41423-024-01220-3","DOIUrl":"10.1038/s41423-024-01220-3","url":null,"abstract":"The potential of macrophage-mediated phagocytosis as a cancer treatment is promising. Blocking the CD47–SIRPα interaction with a CD47-specific antibody significantly enhances macrophage phagocytosis. However, concerns regarding their toxicity to nontumor cells remain substantial. Here, we engineered chimeric antigen receptor macrophages (CAR-Ms) by fusing a humanized single-chain variable fragment with FcγRIIa and integrating short hairpin RNA to silence SIRPα, thereby disrupting the CD47–SIRPα signaling pathway. These modified CAR-shSIRPα-M cells exhibited an M1-like phenotype, superior phagocytic function, substantial cytotoxic effects on HER2-positive tumor cells, and the ability to eliminate patient-derived organoids. In vivo, CAR-M cells significantly inhibited tumor growth and prolonged survival in tumor-bearing mice. Notably, CAR-shSIRPα-M cells enhanced cytotoxic T-cell infiltration into tumors, thereby enhancing the antitumor response in both the humanized immune system mouse model and immunocompetent mice. Mechanistically, SIRPα inhibition activated inflammatory pathways and the cGAS-STING signaling cascade in CAR-M cells, leading to increased production of proinflammatory cytokines, reactive oxygen species, and nitric oxide, thereby enhancing their antitumor effects. These findings underscore the potential of SIRPα inhibition as a novel strategy to increase the antitumor efficacy of CAR-M cells in cancer immunotherapy, particularly against solid tumors.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 11","pages":"1335-1349"},"PeriodicalIF":21.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01220-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388450","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}

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The TET3 inflammasome senses unique long HSV-1 proteins for virus particle budding from the nucleus TET3 炎症体感知独特的 HSV-1 长蛋白，以便病毒粒子从细胞核出芽。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-08 DOI: 10.1038/s41423-024-01221-2

Qiannv Liu, Weitao Li, Yan Qian, Chunlei Wang, Chun Kong, Mengqian Li, Liangliang Sun, Lang Sun, Yanli Pang, Changtao Jiang, Shuo Wang, Pengyan Xia

引用次数: 0

Type 17 immunity: novel insights into intestinal homeostasis and autoimmune pathogenesis driven by gut-primed T cells 17 型免疫：对肠道平衡和肠道刺激 T 细胞驱动的自身免疫发病机制的新认识。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-08 DOI: 10.1038/s41423-024-01218-x

Daiya Ohara, Yusuke Takeuchi, Keiji Hirota

{"title":"Type 17 immunity: novel insights into intestinal homeostasis and autoimmune pathogenesis driven by gut-primed T cells","authors":"Daiya Ohara, Yusuke Takeuchi, Keiji Hirota","doi":"10.1038/s41423-024-01218-x","DOIUrl":"10.1038/s41423-024-01218-x","url":null,"abstract":"The IL-23 signaling pathway in both innate and adaptive immune cells is vital for orchestrating type 17 immunity, which is marked by the secretion of signature cytokines such as IL-17, IL-22, and GM-CSF. These proinflammatory mediators play indispensable roles in maintaining intestinal immune equilibrium and mucosal host defense; however, their involvement has also been implicated in the pathogenesis of chronic inflammatory disorders, such as inflammatory bowel diseases and autoimmunity. However, the implications of type 17 immunity across diverse inflammation models are complex. This review provides a comprehensive overview of the multifaceted roles of these cytokines in maintaining gut homeostasis and in perturbing gut barrier integrity, leading to acute and chronic inflammation in various models of gut infection and colitis. Additionally, this review focuses on type 17 immunity interconnecting multiple organs in autoimmune conditions, with a particular emphasis on the pathogenesis of autoimmune arthritis and neuroinflammation driven by T cells primed within the gut microenvironment.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 11","pages":"1183-1200"},"PeriodicalIF":21.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01218-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388452","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}

引用次数: 0

Author Correction: Fatty acid metabolism constrains Th9 cell differentiation and antitumor immunity via the modulation of retinoic acid receptor signaling 作者更正：脂肪酸代谢通过调节视黄酸受体信号制约 Th9 细胞分化和抗肿瘤免疫力

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-08 DOI: 10.1038/s41423-024-01223-0

Takahiro Nakajima, Toshio Kanno, Yuki Ueda, Keisuke Miyako, Takeru Endo, Souta Yoshida, Satoru Yokoyama, Hikari K. Asou, Kazuko Yamada, Kazutaka Ikeda, Yosuke Togashi, Yusuke Endo

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MLKL-mediated endothelial necroptosis drives vascular damage and mortality in systemic inflammatory response syndrome MLKL 介导的内皮坏死促使全身炎症反应综合征的血管损伤和死亡。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-09-30 DOI: 10.1038/s41423-024-01217-y

Xiaoxia Wu, Xiaoming Zhao, Fang Li, Yang Wang, Yangjing Ou, Haiwei Zhang, Xiaoming Li, Xuanhui Wu, Lingxia Wang, Ming Li, Yue Zhang, Jianling Liu, Mingyan Xing, Han Liu, Yongchang Tan, Yangyang Wang, Yangyang Xie, Hanwen Zhang, Yan Luo, Hong Li, Jing Wang, Liming Sun, Yu Li, Haibing Zhang

{"title":"MLKL-mediated endothelial necroptosis drives vascular damage and mortality in systemic inflammatory response syndrome","authors":"Xiaoxia Wu, Xiaoming Zhao, Fang Li, Yang Wang, Yangjing Ou, Haiwei Zhang, Xiaoming Li, Xuanhui Wu, Lingxia Wang, Ming Li, Yue Zhang, Jianling Liu, Mingyan Xing, Han Liu, Yongchang Tan, Yangyang Wang, Yangyang Xie, Hanwen Zhang, Yan Luo, Hong Li, Jing Wang, Liming Sun, Yu Li, Haibing Zhang","doi":"10.1038/s41423-024-01217-y","DOIUrl":"10.1038/s41423-024-01217-y","url":null,"abstract":"The hypersecretion of cytokines triggers life-threatening systemic inflammatory response syndrome (SIRS), leading to multiple organ dysfunction syndrome (MODS) and mortality. Although both coagulopathy and necroptosis have been identified as important factors in the pathogenesis of SIRS, the specific cell types that undergo necroptosis and the interrelationships between coagulopathy and necroptosis remain unclear. In this study, we utilized visualization analysis via intravital microscopy to demonstrate that both anticoagulant heparin and nonanticoagulant heparin (NAH) pretreatment protect mice against TNF-α-induced mortality in SIRS. Moreover, the deletion of Mlkl or Ripk3 resulted in decreased coagulation and reduced mortality in TNF-α-induced SIRS. These findings suggest that necroptosis plays a key role upstream of coagulation in SIRS-related mortality. Furthermore, using a genetic lineage tracing mouse model (Tie2-Cre;Rosa26-tdT), we tracked endothelial cells (ECs) and verified that EC necroptosis is responsible for the vascular damage observed in TNF-α-treated mice. Importantly, Mlkl deletion in vascular ECs in mice had a similar protective effect against lethal SIRS by blocking EC necroptosis to protect the integrity of the endothelium. Collectively, our findings demonstrated that RIPK3–MLKL-dependent necroptosis disrupted vascular integrity, resulting in coagulopathy and multiorgan failure, eventually leading to mortality in SIRS patients. These results highlight the importance of targeting vascular EC necroptosis for the development of effective treatments for SIRS patients.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 11","pages":"1309-1321"},"PeriodicalIF":21.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342651","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}

引用次数: 0