Nature Immunology最新文献_第5页

SATB1 is a key regulator of quiescence in stem-like CD8+ T cells SATB1是干细胞样CD8+ T细胞静止的关键调节因子

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-22 DOI: 10.1038/s41590-025-02257-w

Siying Lin, Hongshen Niu, Yuqi Zhang, Kexin Gai, Ryan Brown, Ashley Brown, Jian Shen, Ziyang Xu, Ravi K. Shah, Jessica L. Schmeling, Marlenny Vargas-Cortes, Anthony E. Zamora, Terumi Kohwi-Shigematsu, Jie Fan, Bin Zhang, Weiguo Cui

{"title":"SATB1 is a key regulator of quiescence in stem-like CD8+ T cells","authors":"Siying Lin, Hongshen Niu, Yuqi Zhang, Kexin Gai, Ryan Brown, Ashley Brown, Jian Shen, Ziyang Xu, Ravi K. Shah, Jessica L. Schmeling, Marlenny Vargas-Cortes, Anthony E. Zamora, Terumi Kohwi-Shigematsu, Jie Fan, Bin Zhang, Weiguo Cui","doi":"10.1038/s41590-025-02257-w","DOIUrl":"10.1038/s41590-025-02257-w","url":null,"abstract":"Stem-like progenitor CD8+ T (TPRO) cells sustain cytotoxic immunity during chronic infection and cancer through quiescence, multipotency and self-renewal, hallmarks shared with memory T cells. However, how these properties are maintained under persistent antigen stimulation remains unclear. Here we identify the genomic organizer SATB1 as selectively enriched in both TPRO and memory CD8+ T cells. Given its role in promoting quiescence in hematopoietic stem cells, we hypothesized that SATB1 supports CD8+ T cell stemness. Using CD8+ T cell-specific CRISPR deletion of the Satb1 gene, we show that SATB1 is essential for maintaining TPRO cells during chronic lymphocytic choriomeningitis virus infection and for memory CD8+ T cell formation during acute infection. Multi-omic profiling revealed that SATB1 regulates the chromatin accessibility, transcriptional activity and genome architecture of stemness-associated genes including Tcf7, Bach2 and Myb. These findings reveal a critical role for SATB1 in preserving the transcriptional and epigenetic programs that sustain the stem-like state of antigen-specific CD8+ T cells. Cui and colleagues identify the chromatin organizer protein SATB1 as a critical regulator of quiescence in stem-like progenitor CD8+ T cells that arise during chronic viral infection and cancer.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 10","pages":"1737-1751"},"PeriodicalIF":27.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900339","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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Editorial Expression of Concern: Bcl-6 mediates the germinal center B cell phenotype and lymphomagenesis through transcriptional repression of the DNA-damage sensor ATR 编辑关注表达：Bcl-6通过转录抑制dna损伤传感器ATR介导生发中心B细胞表型和淋巴瘤发生

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-20 DOI: 10.1038/s41590-025-02264-x

Stella Maris Ranuncolo, Jose M Polo, Jamil Dierov, Michael Singer, Tracy Kuo, John Greally, Roland Green, Martin Carroll, Ari Melnick

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Author Correction: Membrane metalloprotease TRABD2A restricts HIV-1 progeny production in resting CD4+ T cells by degrading the viral polyprotein Gag 膜金属蛋白酶TRABD2A通过降解病毒多蛋白Gag来限制静息CD4+ T细胞中HIV-1后代的产生

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-20 DOI: 10.1038/s41590-025-02262-z

Guoxin Liang, Li Zhao, Ying Qiao, Wenqing Geng, Xiaowei Zhang, Mei Liu, Jinxiu Dong, Haibo Ding, Hong Sun, Hong Shang

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Loss of YTHDF2 enhances Th9 programming and CAR-Th9 cell antitumor efficacy YTHDF2缺失可增强Th9编程和CAR-Th9细胞抗肿瘤效果。

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-18 DOI: 10.1038/s41590-025-02235-2

Sai Xiao, Songqi Duan, Yaqun Hong, Jianying Zhang, Shoubao Ma, Michael A. Caligiuri, Jianhua Yu

{"title":"Loss of YTHDF2 enhances Th9 programming and CAR-Th9 cell antitumor efficacy","authors":"Sai Xiao, Songqi Duan, Yaqun Hong, Jianying Zhang, Shoubao Ma, Michael A. Caligiuri, Jianhua Yu","doi":"10.1038/s41590-025-02235-2","DOIUrl":"10.1038/s41590-025-02235-2","url":null,"abstract":"CD4+ T cells differentiate into various subsets, including T helper 1 (Th1), Th2, Th9, Th17 and regulatory T (Treg) cells, which are essential for immune responses and cancer immunotherapy. However, the role of RNA N6-methyladenosine (m6A) modification in this differentiation is unclear. Here we show that YTHDF2, an important m6A reader protein known to destabilize m6A-modified mRNA, negatively regulates Th9 cell differentiation. Ablation of Ythdf2 in both mouse and human naive CD4+ T cells promotes Th9 differentiation by stabilizing Gata3 and Smad3 mRNA under interleukin-4 (IL-4) and transforming growth factor β (TGF-β) signaling, respectively. Ythdf2-deficient Th9 cells produce increased amounts of IL-9 and IL-21, leading to increased tumor infiltration and cytotoxicity by CD8+ T cells and natural killer (NK) cells, thereby improving antitumor activity compared with wild-type Th9 cells. Moreover, YTHDF2 depletion in CAR-Th9 cells enhances their immune activation, reduces their terminal differentiation and augments their antitumor efficacy. Targeting YTHDF2 is thereby a promising strategy to enhance Th9 and CAR-Th9 cell-based cancer immunotherapies. The authors show that the m6A reader protein YTHDF2 negatively regulates Th9 cell differentiation and function. Ablation of YTHDF2 promotes antigen-specific Th9 cell and CAR-Th9 cell antitumor activity in solid tumors.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 9","pages":"1501-1515"},"PeriodicalIF":27.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874230","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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The expanding role of the NLRP3 inflammasome from periodic fevers to therapeutic targets NLRP3炎性体的作用从周期性发热扩展到治疗靶点。

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-18 DOI: 10.1038/s41590-025-02230-7

Alexander N. R. Weber, Róisín M. McManus, Veit Hornung, Matthias Geyer, Jasmin B. Kuemmerle-Deschner, Eicke Latz

{"title":"The expanding role of the NLRP3 inflammasome from periodic fevers to therapeutic targets","authors":"Alexander N. R. Weber, Róisín M. McManus, Veit Hornung, Matthias Geyer, Jasmin B. Kuemmerle-Deschner, Eicke Latz","doi":"10.1038/s41590-025-02230-7","DOIUrl":"10.1038/s41590-025-02230-7","url":null,"abstract":"Understanding and treating inflammation has proven a formidable challenge. The initiator and central motor of inflammation, the protein NLRP3, is an innate immune sentinel and nonspecific sensor of cellular perturbation. A wide array of inflammatory triggers prompts the formation of an NLRP3 ‘inflammasome’ complex, leading to inflammatory interleukin-1 family cytokine release and pyroptotic cell death. Since gain-of-function mutations in NLRP3 were demonstrated to cause a rare autoinflammatory disease termed cryopyrin-associated periodic syndrome, NLRP3 has emerged as key mediator of inflammation in mouse models for many common diseases, including atherosclerosis, Alzheimer’s disease and gout. But even though small-molecule NLRP3 modulators have entered clinical development, many aspects of NLRP3 activation and regulation in humans remain relatively unclear. This Review summarizes the current understanding of the molecular mechanisms that drive NLRP3 inflammasome activation and regulation, and discusses emerging targeting strategies. Understanding these processes can guide precision medicine approaches aimed at mitigating NLRP3-driven pathologies. Latz et al. review the molecular mechanisms that drive NLRP3 inflammasome activation and regulation, and discuss emerging targeting strategies.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 9","pages":"1453-1466"},"PeriodicalIF":27.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874231","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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A little less reading, a little more type 9 action 少一点阅读，多一点9型动作。

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-18 DOI: 10.1038/s41590-025-02253-0

Kaitlyn G. Jackson, Mark H. Kaplan

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IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-15 DOI: 10.1038/s41590-025-02243-2

Jazib Uddin, Hiroshi Yano, Christopher N. Parkhurst, Wen Zhang, Anees Ahmed, Victoria Ribeiro de Godoy, Qianru Wei, Rohit Panchakshari, Antoine Henninot, Surya Dasgupta, Stephen Gaudino, Elizabeth R. Emanuel, Peng Zeng, Isabella Miranda, Elin Hu, Amy M. Tsou, JRI Live Cell Bank, David Artis

{"title":"CGRP-related neuropeptide adrenomedullin 2 promotes tissue-protective ILC2 responses and limits intestinal inflammation","authors":"Jazib Uddin, Hiroshi Yano, Christopher N. Parkhurst, Wen Zhang, Anees Ahmed, Victoria Ribeiro de Godoy, Qianru Wei, Rohit Panchakshari, Antoine Henninot, Surya Dasgupta, Stephen Gaudino, Elizabeth R. Emanuel, Peng Zeng, Isabella Miranda, Elin Hu, Amy M. Tsou, JRI Live Cell Bank, David Artis","doi":"10.1038/s41590-025-02243-2","DOIUrl":"10.1038/s41590-025-02243-2","url":null,"abstract":"Neuro–immune circuits regulate innate and adaptive immunity at barrier surfaces. However, the differential impact of these circuits on proinflammatory versus tissue-protective responses remains poorly defined. We demonstrate that enteric neurons produce calcitonin gene-related peptide-related adrenomedullin 2 (ADM2) and identify a previously unrecognized role for the ADM2 pathway in promoting intestinal tissue-protective functions of group 2 innate lymphoid cells (ILC2s). Genomic or ILC2-intrinsic deletion of ADM2 receptor subunits resulted in a significant reduction in tissue-protective ILC2 responses, defective amphiregulin (AREG) production and increased susceptibility to intestinal damage and inflammation. Conversely, therapeutic delivery of recombinant ADM2 elicited tissue-protective AREG+ ILC2s and limited intestinal inflammation. Expression of genes encoding human ADM2 receptor (CALCRL and RAMP3) was altered in participants with inflammatory bowel diseases and associated with reduced expression of AREG in ILC2s. Collectively, these findings identify that the ADM2–ADM2 receptor pathway can promote tissue-protective functions of ILC2s in the context of intestinal damage and inflammation. Artis and colleagues show that enteric neurons produce CGRP-related ADM2 to promote intestinal tissue-protective functions in ILC2s.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 9","pages":"1516-1526"},"PeriodicalIF":27.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851725","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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TNF gives plasmacytoid dendritic cells a new life TNF赋予浆细胞样树突状细胞新的生命

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-15 DOI: 10.1038/s41590-025-02254-z

Elodie Segura

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Clock genes tune plasticity of group 3 innate lymphoid cells 时钟基因调节第3组先天淋巴样细胞的可塑性

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-13 DOI: 10.1038/s41590-025-02245-0

Siu Ling Tai, Louis Ngai, Arthur Mortha

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Circadian circuits control plasticity of group 3 innate lymphoid cells by sustaining epigenetic configuration of RORγt 生理回路通过维持rr γ - t的表观遗传结构来控制第3组先天淋巴样细胞的可塑性

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-13 DOI: 10.1038/s41590-025-02240-5

Bishan Bhattarai, Alina Ulezko Antonova, Jose L. Fachi, Leone S. Hopkins, Matthew V. D. McCullen, Ankita Saini, Sarah de Oliveira, Wandy L. Beatty, Erik S. Musiek, Vijay K. Kuchroo, Mitchell A. Lazar, Eugene M. Oltz, Marco Colonna

{"title":"Circadian circuits control plasticity of group 3 innate lymphoid cells by sustaining epigenetic configuration of RORγt","authors":"Bishan Bhattarai, Alina Ulezko Antonova, Jose L. Fachi, Leone S. Hopkins, Matthew V. D. McCullen, Ankita Saini, Sarah de Oliveira, Wandy L. Beatty, Erik S. Musiek, Vijay K. Kuchroo, Mitchell A. Lazar, Eugene M. Oltz, Marco Colonna","doi":"10.1038/s41590-025-02240-5","DOIUrl":"10.1038/s41590-025-02240-5","url":null,"abstract":"The gut experiences daily fluctuations in microbes and nutrients aligned with circadian rhythms that regulate nutrient absorption and immune function. Group 3 innate lymphoid cells (ILC3s) support gut homeostasis through interleukin-22 (IL-22) but can convert into interferon-γ-producing ILC1s. How circadian proteins control this plasticity remains unclear. Here we showed that the circadian proteins REV-ERBα and REV-ERBβ maintain ILC3 identity. Their combined deletion promoted ILC3-to-ILC1 conversion, reduced energy metabolism and IL-22 production, increased interferon-γ production, and heightened susceptibility to Citrobacter rodentium infection. Single-cell multiomics and gene editing revealed that REV-ERBα/REV-ERBβ deficiency upregulated the transcription factor NFIL3, which repressed the expression of RORγt via a –2-kb cis-regulatory element in the Rorc gene, shifting cells toward a T-bet-driven state. Chromatin and metabolic analyses indicated that REV-ERBα/REV-ERBβ loss reprogrammed regulatory and metabolic circuits. Thus, REV-ERBα/REV-ERBβ safeguard gut integrity by regulating clock genes that control RORγt expression and preserve ILC3 identity and resistance to intestinal inflammation. Colonna and colleagues show that the clock genes encoding REV-ERBα and REV-ERBβ maintain ILC3 functions in the gut by controlling the expression of RORγt.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 9","pages":"1527-1539"},"PeriodicalIF":27.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825387","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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