Cellular &Molecular Immunology最新文献_第8页

Immunopeptidome mining reveals a novel ERS-induced target in T1D 免疫肽组挖掘揭示 T1D 中 ERS 诱导的新靶点

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-04-30 DOI: 10.1038/s41423-024-01150-0

Lina Wang, Shushu Yang, Gaohui Zhu, Jie Li, Gang Meng, Xiaoling Chen, Mengjun Zhang, Shufeng Wang, Xiangqian Li, Yu Pan, Yi Huang, Li Wang, Yuzhang Wu

{"title":"Immunopeptidome mining reveals a novel ERS-induced target in T1D","authors":"Lina Wang, Shushu Yang, Gaohui Zhu, Jie Li, Gang Meng, Xiaoling Chen, Mengjun Zhang, Shufeng Wang, Xiangqian Li, Yu Pan, Yi Huang, Li Wang, Yuzhang Wu","doi":"10.1038/s41423-024-01150-0","DOIUrl":"10.1038/s41423-024-01150-0","url":null,"abstract":"Autoreactive CD8+ T cells play a key role in type 1 diabetes (T1D), but the antigen spectrum that activates autoreactive CD8+ T cells remains unclear. Endoplasmic reticulum stress (ERS) has been implicated in β-cell autoantigen generation. Here, we analyzed the major histocompatibility complex class I (MHC-I)-associated immunopeptidome (MIP) of islet β-cells under steady and ERS conditions and found that ERS reshaped the MIP of β-cells and promoted the MHC-I presentation of a panel of conventional self-peptides. Among them, OTUB258-66 showed immunodominance, and the corresponding autoreactive CD8+ T cells were diabetogenic in nonobese diabetic (NOD) mice. High glucose intake upregulated pancreatic OTUB2 expression and amplified the OTUB258-66-specific CD8+ T-cell response in NOD mice. Repeated OTUB258-66 administration significantly reduced the incidence of T1D in NOD mice. Interestingly, peripheral blood mononuclear cells (PBMCs) from patients with T1D, but not from healthy controls, showed a positive IFN-γ response to human OTUB2 peptides. This study provides not only a new explanation for the role of ERS in promoting β-cell-targeted autoimmunity but also a potential target for the prevention and treatment of T1D. The data are available via ProteomeXchange with the identifier PXD041227.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831207","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

Tissue-specific features of innate lymphoid cells in antiviral defense 先天性淋巴细胞在抗病毒防御中的组织特异性特征

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-04-29 DOI: 10.1038/s41423-024-01161-x

Sytse J. Piersma

引用次数: 0

Inhibition of METTL3 in macrophages provides protection against intestinal inflammation 抑制巨噬细胞中的 METTL3 可防止肠道炎症

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-04-22 DOI: 10.1038/s41423-024-01156-8

Huilong Yin, Zhuan Ju, Xiang Zhang, Wenjie Zuo, Yuhang Yang, Minhua Zheng, Xiaofang Zhang, Yuning Liu, Yingran Peng, Ying Xing, Angang Yang, Rui Zhang

{"title":"Inhibition of METTL3 in macrophages provides protection against intestinal inflammation","authors":"Huilong Yin, Zhuan Ju, Xiang Zhang, Wenjie Zuo, Yuhang Yang, Minhua Zheng, Xiaofang Zhang, Yuning Liu, Yingran Peng, Ying Xing, Angang Yang, Rui Zhang","doi":"10.1038/s41423-024-01156-8","DOIUrl":"10.1038/s41423-024-01156-8","url":null,"abstract":"Inflammatory bowel disease (IBD) is prevalent, and no satisfactory therapeutic options are available because the mechanisms underlying its development are poorly understood. In this study, we discovered that increased expression of methyltransferase-like 3 (METTL3) in macrophages was correlated with the development of colitis and that depletion of METTL3 in macrophages protected mice against dextran sodium sulfate (DSS)-induced colitis. Mechanistic characterization indicated that METTL3 depletion increased the YTHDF3-mediated expression of phosphoglycolate phosphatase (PGP), which resulted in glucose metabolism reprogramming and the suppression of CD4+ T helper 1 (Th1) cell differentiation. Further analysis revealed that glucose metabolism contributed to the ability of METTL3 depletion to ameliorate colitis symptoms. In addition, we developed two potent small molecule METTL3 inhibitors, namely, F039-0002 and 7460-0250, that strongly ameliorated DSS-induced colitis. Overall, our study suggests that METTL3 plays crucial roles in the progression of colitis and highlights the potential of targeting METTL3 to attenuate intestinal inflammation for the treatment of colitis.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140636048","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

Lkb1 orchestrates γδ T-cell metabolic and functional fitness to control IL-17-mediated autoimmune hepatitis Lkb1 协调γδ T 细胞的代谢和功能，控制 IL-17 介导的自身免疫性肝炎

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-04-19 DOI: 10.1038/s41423-024-01163-9

Zhiqiang Xiao, Shanshan Wang, Liang Luo, Wenkai Lv, Peiran Feng, Yadong Sun, Quanli Yang, Jun He, Guangchao Cao, Zhinan Yin, Meixiang Yang

{"title":"Lkb1 orchestrates γδ T-cell metabolic and functional fitness to control IL-17-mediated autoimmune hepatitis","authors":"Zhiqiang Xiao, Shanshan Wang, Liang Luo, Wenkai Lv, Peiran Feng, Yadong Sun, Quanli Yang, Jun He, Guangchao Cao, Zhinan Yin, Meixiang Yang","doi":"10.1038/s41423-024-01163-9","DOIUrl":"10.1038/s41423-024-01163-9","url":null,"abstract":"γδ T cells play a crucial role in immune surveillance and serve as a bridge between innate and adaptive immunity. However, the metabolic requirements and regulation of γδ T-cell development and function remain poorly understood. In this study, we investigated the role of liver kinase B1 (Lkb1), a serine/threonine kinase that links cellular metabolism with cell growth and proliferation, in γδ T-cell biology. Our findings demonstrate that Lkb1 is not only involved in regulating γδ T lineage commitment but also plays a critical role in γδ T-cell effector function. Specifically, T-cell-specific deletion of Lkb1 resulted in impaired thymocyte development and distinct alterations in γδ T-cell subsets in both the thymus and peripheral lymphoid tissues. Notably, loss of Lkb1 inhibited the commitment of Vγ1 and Vγ4 γδ T cells, promoted the maturation of IL-17-producing Vγ6 γδ T cells, and led to the occurrence of fatal autoimmune hepatitis (AIH). Notably, clearance of γδ T cells or blockade of IL-17 significantly attenuated AIH. Mechanistically, Lkb1 deficiency disrupted metabolic homeostasis and AMPK activity, accompanied by increased mTORC1 activation, thereby causing overactivation of γδ T cells and enhanced apoptosis. Interestingly, activation of AMPK or suppression of mTORC1 signaling effectively inhibited IL-17 levels and attenuated AIH in Lkb1-deficient mice. Our findings highlight the pivotal role of Lkb1 in maintaining the homeostasis of γδ T cells and preventing IL-17-mediated autoimmune diseases, providing new insights into the metabolic programs governing the subset determination and functional differentiation of thymic γδ T cells.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624192","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

Targeting macrophage metabolism to enhance tumor immunotherapy 以巨噬细胞代谢为靶点加强肿瘤免疫疗法

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-04-17 DOI: 10.1038/s41423-024-01149-7

Jing Liu, Zhibo Ma, Wenlong Jia, Peixiang Lan

引用次数: 0

Neuropilin-1high monocytes protect against neonatal inflammation 神经纤蛋白-1 高的单核细胞可防止新生儿发炎

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-04-17 DOI: 10.1038/s41423-024-01157-7

Xiaoqing Zheng, Wen Lei, Yongmei Zhang, Han Jin, Cha Han, Fan Wu, Chonghong Jia, Ruihong Zeng, Zhanghua Chen, Yuxia Zhang, Haitao Wang, Qiang Liu, Zhi Yao, Ying Yu, Jie Zhou

{"title":"Neuropilin-1high monocytes protect against neonatal inflammation","authors":"Xiaoqing Zheng, Wen Lei, Yongmei Zhang, Han Jin, Cha Han, Fan Wu, Chonghong Jia, Ruihong Zeng, Zhanghua Chen, Yuxia Zhang, Haitao Wang, Qiang Liu, Zhi Yao, Ying Yu, Jie Zhou","doi":"10.1038/s41423-024-01157-7","DOIUrl":"10.1038/s41423-024-01157-7","url":null,"abstract":"Neonates are susceptible to inflammatory disorders such as necrotizing enterocolitis (NEC) due to their immature immune system. The timely appearance of regulatory immune cells in early life contributes to the control of inflammation in neonates, yet the underlying mechanisms of which remain poorly understood. In this study, we identified a subset of neonatal monocytes characterized by high levels of neuropilin-1 (Nrp1), termed Nrp1high monocytes. Compared with their Nrp1low counterparts, Nrp1high monocytes displayed potent immunosuppressive activity. Nrp1 deficiency in myeloid cells aggravated the severity of NEC, whereas adoptive transfer of Nrp1high monocytes led to remission of NEC. Mechanistic studies showed that Nrp1, by binding to its ligand Sema4a, induced intracellular p38-MAPK/mTOR signaling and activated the transcription factor KLF4. KLF4 transactivated Nos2 and enhanced the production of nitric oxide (NO), a key mediator of immunosuppression in monocytes. These findings reveal an important immunosuppressive axis in neonatal monocytes and provide a potential therapeutic strategy for treating inflammatory disorders in neonates.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140615913","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

Bypassing PELO-mediated ATPase activation of the NLR is a common pathogenic cause of NLR-associated autoinflammatory diseases 绕过 PELO 介导的 NLR ATPase 激活是 NLR 相关自身炎症性疾病的常见致病原因

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-04-17 DOI: 10.1038/s41423-024-01162-w

Xiurong Wu, Zhang-Hua Yang, Yue Zheng, Jianfeng Wu, Jiahuai Han

引用次数: 0

Synthetic biology approaches for improving the specificity and efficacy of cancer immunotherapy 提高癌症免疫疗法特异性和疗效的合成生物学方法

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-04-11 DOI: 10.1038/s41423-024-01153-x

Bo Zhu, Hang Yin, Di Zhang, Meiling Zhang, Xiaojuan Chao, Luca Scimeca, Ming-Ru Wu

{"title":"Synthetic biology approaches for improving the specificity and efficacy of cancer immunotherapy","authors":"Bo Zhu, Hang Yin, Di Zhang, Meiling Zhang, Xiaojuan Chao, Luca Scimeca, Ming-Ru Wu","doi":"10.1038/s41423-024-01153-x","DOIUrl":"10.1038/s41423-024-01153-x","url":null,"abstract":"Immunotherapy has shown robust efficacy in treating a broad spectrum of hematological and solid cancers. Despite the transformative impact of immunotherapy on cancer treatment, several outstanding challenges remain. These challenges include on-target off-tumor toxicity, systemic toxicity, and the complexity of achieving potent and sustainable therapeutic efficacy. Synthetic biology has emerged as a promising approach to overcome these obstacles, offering innovative tools for engineering living cells with customized functions. This review provides an overview of the current landscape and future prospects of cancer immunotherapy, particularly emphasizing the role of synthetic biology in augmenting its specificity, controllability, and efficacy. We delineate and discuss two principal synthetic biology strategies: those targeting tumor surface antigens with engineered immune cells and those detecting intratumoral disease signatures with engineered gene circuits. This review concludes with a forward-looking perspective on the enduring challenges in cancer immunotherapy and the potential breakthroughs that synthetic biology may contribute to the field.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01153-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581774","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

GSNOR negatively regulates the NLRP3 inflammasome via S-nitrosation of MAPK14 GSNOR 通过 S-亚硝基化 MAPK14 负向调节 NLRP3 炎症体

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-04-03 DOI: 10.1038/s41423-024-01155-9

Qianjin Liu, Lijin Jiao, Mao-Sen Ye, Zhiyu Ma, Jinsong Yu, Ling-Yan Su, Wei-Yin Zou, Lu-Xiu Yang, Chang Chen, Yong-Gang Yao

{"title":"GSNOR negatively regulates the NLRP3 inflammasome via S-nitrosation of MAPK14","authors":"Qianjin Liu, Lijin Jiao, Mao-Sen Ye, Zhiyu Ma, Jinsong Yu, Ling-Yan Su, Wei-Yin Zou, Lu-Xiu Yang, Chang Chen, Yong-Gang Yao","doi":"10.1038/s41423-024-01155-9","DOIUrl":"10.1038/s41423-024-01155-9","url":null,"abstract":"Hyperactivation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous diseases. However, the precise molecular mechanisms that modulate the transcriptional regulation of NLRP3 remain largely unknown. In this study, we demonstrated that S-nitrosoglutathione reductase (GSNOR) deficiency in macrophages leads to significant increases in the Nlrp3 and Il-1β expression levels and interleukin-1β (IL-1β) secretion in response to NLRP3 inflammasome stimulation. Furthermore, in vivo experiments utilizing Gsnor−/− mice revealed increased disease severity in both lipopolysaccharide (LPS)-induced septic shock and dextran sodium sulfate (DSS)-induced colitis models. Additionally, we showed that both LPS-induced septic shock and DSS-induced colitis were ameliorated in Gsnor−/− Nlrp3−/− double-knockout (DKO) mice. Mechanistically, GSNOR deficiency increases the S-nitrosation of mitogen-activated protein kinase 14 (MAPK14) at the Cys211 residue and augments MAPK14 kinase activity, thereby promoting Nlrp3 and Il-1β transcription and stimulating NLRP3 inflammasome activity. Our findings suggested that GSNOR is a regulator of the NLRP3 inflammasome and that reducing the level of S-nitrosylated MAPK14 may constitute an effective strategy for alleviating diseases associated with NLRP3-mediated inflammation.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581781","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

Cellular metabolism regulates the differentiation and function of T-cell subsets 细胞代谢调节 T 细胞亚群的分化和功能

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-04-02 DOI: 10.1038/s41423-024-01148-8

Sicong Ma, Yanan Ming, Jingxia Wu, Guoliang Cui

{"title":"Cellular metabolism regulates the differentiation and function of T-cell subsets","authors":"Sicong Ma, Yanan Ming, Jingxia Wu, Guoliang Cui","doi":"10.1038/s41423-024-01148-8","DOIUrl":"10.1038/s41423-024-01148-8","url":null,"abstract":"T cells are an important component of adaptive immunity and protect the host from infectious diseases and cancers. However, uncontrolled T cell immunity may cause autoimmune disorders. In both situations, antigen-specific T cells undergo clonal expansion upon the engagement and activation of antigens. Cellular metabolism is reprogrammed to meet the increase in bioenergetic and biosynthetic demands associated with effector T cell expansion. Metabolites not only serve as building blocks or energy sources to fuel cell growth and expansion but also regulate a broad spectrum of cellular signals that instruct the differentiation of multiple T cell subsets. The realm of immunometabolism research is undergoing swift advancements. Encapsulating all the recent progress within this concise review in not possible. Instead, our objective is to provide a succinct introduction to this swiftly progressing research, concentrating on the metabolic intricacies of three pivotal nutrient classes—lipids, glucose, and amino acids—in T cells. We shed light on recent investigations elucidating the roles of these three groups of metabolites in mediating the metabolic and immune functions of T cells. Moreover, we delve into the prospect of “editing” metabolic pathways within T cells using pharmacological or genetic approaches, with the aim of synergizing this approach with existing immunotherapies and enhancing the efficacy of antitumor and antiinfection immune responses.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01148-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602086","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