Cellular &Molecular Immunology最新文献_第7页

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}

引用次数: 0

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}

引用次数: 0

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

引用次数: 0

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

Hepatocellular carcinoma-specific epigenetic checkpoints bidirectionally regulate the antitumor immunity of CD4 + T cells 肝细胞癌特异性表观遗传检查点双向调节 CD4 + T 细胞的抗肿瘤免疫力

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-09-19 DOI: 10.1038/s41423-024-01215-0

Shuai Wang, Lijun Meng, Nan Xu, Huan Chen, Zhaofeng Xiao, Di Lu, Xiaohui Fan, Limin Xia, Jun Chen, Shusen Zheng, Qiang Wei, Xuyong Wei, Xiao Xu

{"title":"Hepatocellular carcinoma-specific epigenetic checkpoints bidirectionally regulate the antitumor immunity of CD4 + T cells","authors":"Shuai Wang, Lijun Meng, Nan Xu, Huan Chen, Zhaofeng Xiao, Di Lu, Xiaohui Fan, Limin Xia, Jun Chen, Shusen Zheng, Qiang Wei, Xuyong Wei, Xiao Xu","doi":"10.1038/s41423-024-01215-0","DOIUrl":"10.1038/s41423-024-01215-0","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a highly malignant tumor with significant global health implications. The role of CD4+ T cells, particularly conventional CD4+ T cells (Tconvs), in HCC progression remains unexplored. Furthermore, epigenetic factors are crucial in immune regulation, yet their specific role in HCC-infiltrating Tconv cells remains elusive. This study elucidates the role of MATR3, an epigenetic regulator, in modulating Tconv activity and immune evasion within the HCC microenvironment. Reanalysis of the scRNA-seq data revealed that early activation of CD4+ T cells is crucial for establishing an antitumor immune response. In vivo and in vitro experiments revealed that Tconv enhances cDC1-induced CD8+ T-cell activation. Screening identified MATR3 as a critical regulator of Tconv function, which is necessary for antitumour activity but harmful when overexpressed. Excessive MATR3 expression exacerbates Tconv exhaustion and impairs function by recruiting the SWI/SNF complex to relax chromatin in the TOX promoter region, leading to aberrant transcriptional changes. In summary, MATR3 is an HCC-specific epigenetic checkpoint that bidirectionally regulates Tconv antitumour immunity, suggesting new therapeutic strategies targeting epigenetic regulators to enhance antitumour immunity in HCC.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 11","pages":"1296-1308"},"PeriodicalIF":21.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255262","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

Author Correction: Priming with FLO8-deficient Candida albicans induces Th1-biased protective immunity against lethal polymicrobial sepsis 作者更正：用FLO8缺陷的白色念珠菌诱导Th1型保护性免疫，对抗致命的多微生物败血症

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-09-10 DOI: 10.1038/s41423-024-01214-1

Quan-Zhen Lv, De-Dong Li, Hua Han, Yi-Heng Yang, Jie-Lin Duan, Hui-Hui Ma, Yao Yu, Jiang-Ye Chen, Yuan-Ying Jiang, Xin-Ming Jia

引用次数: 0

Rack1 regulates B-cell development and function by binding to and stabilizing the transcription factor Pax5 Rack1 通过与转录因子 Pax5 结合并使其稳定来调控 B 细胞的发育和功能

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-09-10 DOI: 10.1038/s41423-024-01213-2

Xueting Zhang, Chenke Ma, Yuchen Lu, Jing Wang, Hongfang Yun, Hui Jiang, Mengyao Wu, Xiaoyao Feng, Wenbin Gai, Guanglei Xu, Hongbin Deng, Jiannan Feng, Wanli Liu, Taoxing Shi, Qianqian Cheng, Jiyan Zhang

{"title":"Rack1 regulates B-cell development and function by binding to and stabilizing the transcription factor Pax5","authors":"Xueting Zhang, Chenke Ma, Yuchen Lu, Jing Wang, Hongfang Yun, Hui Jiang, Mengyao Wu, Xiaoyao Feng, Wenbin Gai, Guanglei Xu, Hongbin Deng, Jiannan Feng, Wanli Liu, Taoxing Shi, Qianqian Cheng, Jiyan Zhang","doi":"10.1038/s41423-024-01213-2","DOIUrl":"10.1038/s41423-024-01213-2","url":null,"abstract":"The transcription factor Pax5 activates genes essential for B-cell development and function. However, the regulation of Pax5 expression remains elusive. The adaptor Rack1 can interact with multiple transcription factors and modulate their activation and/or stability. However, its role in the transcriptional control of B-cell fates is largely unknown. Here, we show that CD19-driven Rack1 deficiency leads to pro-B accumulation and a simultaneous reduction in B cells at later developmental stages. The generation of bone marrow chimeras indicates a cell-intrinsic role of Rack1 in B-cell homeostasis. Moreover, Rack1 augments BCR and TLR signaling in mature B cells. On the basis of the aberrant expression of Pax5-regulated genes, including CD19, upon Rack1 deficiency, further exploration revealed that Rack1 maintains the protein level of Pax5 through direct interaction and consequently prevents Pax5 ubiquitination. Accordingly, Mb1-driven Rack1 deficiency almost completely blocks B-cell development at the pro-B-cell stage. Ectopic expression of Pax5 in Rack1-deficient pro-B cells partially rescues B-cell development. Thus, Rack1 regulates B-cell development and function through, at least partially, binding to and stabilizing Pax5.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 11","pages":"1282-1295"},"PeriodicalIF":21.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142207644","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

RBM25 is required to restrain inflammation via ACLY RNA splicing-dependent metabolism rewiring 需要 RBM25 通过 ACLY RNA 剪接依赖性新陈代谢重新布线来抑制炎症

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-09-09 DOI: 10.1038/s41423-024-01212-3

Yunkai Zhang, Ying Gao, Yujia Wang, Yuyu Jiang, Yan Xiang, Xiaohui Wang, Zeting Wang, Yingying Ding, Huiying Chen, Bing Rui, Wanwan Huai, Boyu Cai, Xiaomeng Ren, Feng Ma, Sheng Xu, Zhenzhen Zhan, Xingguang Liu

{"title":"RBM25 is required to restrain inflammation via ACLY RNA splicing-dependent metabolism rewiring","authors":"Yunkai Zhang, Ying Gao, Yujia Wang, Yuyu Jiang, Yan Xiang, Xiaohui Wang, Zeting Wang, Yingying Ding, Huiying Chen, Bing Rui, Wanwan Huai, Boyu Cai, Xiaomeng Ren, Feng Ma, Sheng Xu, Zhenzhen Zhan, Xingguang Liu","doi":"10.1038/s41423-024-01212-3","DOIUrl":"10.1038/s41423-024-01212-3","url":null,"abstract":"Spliceosome dysfunction and aberrant RNA splicing underline unresolved inflammation and immunopathogenesis. Here, we revealed the misregulation of mRNA splicing via the spliceosome in the pathogenesis of rheumatoid arthritis (RA). Among them, decreased expression of RNA binding motif protein 25 (RBM25) was identified as a major pathogenic factor in RA patients and experimental arthritis mice through increased proinflammatory mediator production and increased hyperinflammation in macrophages. Multiomics analyses of macrophages from RBM25-deficient mice revealed that the transcriptional enhancement of proinflammatory genes (including Il1b, Il6, and Cxcl10) was coupled with histone 3 lysine 9 acetylation (H3K9ac) and H3K27ac modifications as well as hypoxia inducible factor-1α (HIF-1α) activity. Furthermore, RBM25 directly bound to and mediated the 14th exon skipping of ATP citrate lyase (Acly) pre-mRNA, resulting in two distinct Acly isoforms, Acly Long (Acly L) and Acly Short (Acly S). In proinflammatory macrophages, Acly L was subjected to protein lactylation on lysine 918/995, whereas Acly S did not, which influenced its affinity for metabolic substrates and subsequent metabolic activity. RBM25 deficiency overwhelmingly increased the expression of the Acly S isoform, enhancing glycolysis and acetyl-CoA production for epigenetic remodeling, macrophage overactivation and tissue inflammatory injury. Finally, macrophage-specific deletion of RBM25 led to inflammaging, including spontaneous arthritis in various joints of mice and inflammation in multiple organs, which could be relieved by pharmacological inhibition of Acly. Overall, targeting the RBM25-Acly splicing axis represents a potential strategy for modulating macrophage responses in autoimmune arthritis and aging-associated inflammation.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 11","pages":"1231-1250"},"PeriodicalIF":21.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142207645","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