Nature Immunology最新文献_第6页

A critical role of N4-acetylation of cytidine in mRNA by NAT10 in T cell expansion and antiviral immunity 胞苷mRNA被NAT10乙酰化在T细胞扩增和抗病毒免疫中的关键作用

IF 27.7 1区医学

Nature Immunology Pub Date : 2025-03-05 DOI: 10.1038/s41590-025-02100-2

Lu Sun, Xiaoyan Li, Feixiang Xu, Yuwen Chen, Xushuo Li, Zhicheng Yang, Ying Yang, Ke Wang, Tianyi Ren, Zihao Lin, Hua Wang, Xiangdong Wang, Yan Lu, Zhenju Song, Zhou-Li Cheng, Duojiao Wu

{"title":"A critical role of N4-acetylation of cytidine in mRNA by NAT10 in T cell expansion and antiviral immunity","authors":"Lu Sun, Xiaoyan Li, Feixiang Xu, Yuwen Chen, Xushuo Li, Zhicheng Yang, Ying Yang, Ke Wang, Tianyi Ren, Zihao Lin, Hua Wang, Xiangdong Wang, Yan Lu, Zhenju Song, Zhou-Li Cheng, Duojiao Wu","doi":"10.1038/s41590-025-02100-2","DOIUrl":"10.1038/s41590-025-02100-2","url":null,"abstract":"Following activation, naive T cells exit quiescence and require global translation for rapid expansion, yet the underlying mechanisms remain unclear. Here, we show that during T cell activation, cells upregulate the expression of N-acetyltransferase 10 (NAT10), an enzyme responsible for N4-acetylcytidine (ac4C) modification of mRNAs. ac4C-modified Myc mRNAs show higher translation efficiency, enabling rapid synthesis of MYC protein and supporting robust T cell expansion. Conditional deletion of Nat10 in mouse T cells causes severe cell cycle arrest and limitation of cell expansion due to MYC deficiency, ultimately exacerbating infection in an acute lymphocytic choriomeningitis virus model. Additionally, T cells from older individuals with lower NAT10 levels show proliferative defects, which may partially account for impaired antiviral responses in older individuals. This study reveals a mechanism governing T cell expansion, signal-dependent mRNA degradation induction and the potential in vivo biological significance of ac4C modification in T cell-mediated immune responses. The authors show that NAT10 is upregulated with T cell antigen receptor signaling and that T cell-specific NAT10 deficiency results in diminished numbers of naive T cells, translating to an inability to mount a significant antiviral T cell response.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 4","pages":"619-634"},"PeriodicalIF":27.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-025-02100-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545995","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

Enhancing T cell therapy 加强T细胞治疗

IF 27.7 1区医学

Nature Immunology Pub Date : 2025-03-03 DOI: 10.1038/s41590-025-02109-7

Nicholas J. Bernard

引用次数: 0

Enteric GABAergic neuron-derived γ-aminobutyric acid initiates expression of Igfbp7 to sustain ILC3 homeostasis 肠内gaba能神经元来源的γ-氨基丁酸启动Igfbp7的表达以维持ILC3的稳态

IF 27.7 1区医学

Nature Immunology Pub Date : 2025-03-03 DOI: 10.1038/s41590-025-02081-2

Nian Liu, Jiacheng He, Yanmei Yang, Yunlong Wang, Lingwei Zhang, Ziqi Xiao, Zhen Xiong, Shangxun Zhong, Yuwei Xu, Yang Gu, Jianyi Wang, Yufei Lan, Ying Du, Pingping Zhu, Zhi Zhang, Xinjuan Fan, Benyu Liu, Zusen Fan

{"title":"Enteric GABAergic neuron-derived γ-aminobutyric acid initiates expression of Igfbp7 to sustain ILC3 homeostasis","authors":"Nian Liu, Jiacheng He, Yanmei Yang, Yunlong Wang, Lingwei Zhang, Ziqi Xiao, Zhen Xiong, Shangxun Zhong, Yuwei Xu, Yang Gu, Jianyi Wang, Yufei Lan, Ying Du, Pingping Zhu, Zhi Zhang, Xinjuan Fan, Benyu Liu, Zusen Fan","doi":"10.1038/s41590-025-02081-2","DOIUrl":"10.1038/s41590-025-02081-2","url":null,"abstract":"Neuronal signals have emerged as critical factors that regulate group 3 innate lymphoid cell (ILC3) response and tissue homeostasis, but the molecular mechanisms underlying this regulation remain largely elusive. Here, we identified that the enteric GABAergic neuron-derived neurotransmitter γ-aminobutyric acid (GABA) inhibited proliferation and IL-17A production in ILC3s in a manner dependent on the GABA receptors Gabbr1 and Gabbr2. Conditional deletion of Gabbr1 or ablation of GABAergic neurons caused increased IL-17A production and aggravated colitis. Mechanistically, GABA suppressed the expression of the LIP isoform of the transcription factor C/EBP-β in ILC3s, which repressed the transcription of Igfbp7, which encodes the secreted factor Igfbp7. Autocrine Igfbp7 signaling through the receptor Igf1R inhibited ILC3 proliferation and IL-17A production. Suppression of signaling through the GABA-C/EBP-β-IGFBP7 pathway highly correlated with severity of intestinal inflammation in patients with inflammatory bowel disease (IBD). Collectively, our findings describe an important molecular mechanism underlying the maintenance of gut immune homeostasis. Fan and colleagues show that the neurotransmitter GABA signals in intestinal ILC3s to suppress IL-17A production through a regulatory loop that involves suppression of C/EBP-β and induction of Igfb7.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 3","pages":"404-415"},"PeriodicalIF":27.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-025-02081-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536140","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

Enteric cross-talk 肠相声

IF 27.7 1区医学

Nature Immunology Pub Date : 2025-03-03 DOI: 10.1038/s41590-025-02107-9

Ioana Staicu

引用次数: 0

Tissue directives 组织指令

IF 27.7 1区医学

Nature Immunology Pub Date : 2025-03-03 DOI: 10.1038/s41590-025-02108-8

Laurie A. Dempsey

引用次数: 0

Gut GABA keeps ILC3s in check 肠道GABA可以控制ilc3