Nature Immunology最新文献_第8页

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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Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age 多模态分析揭示了人类免疫细胞随年龄变化的组织定向特征

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-13 DOI: 10.1038/s41590-025-02241-4

Steven B. Wells, Daniel B. Rainbow, Michal Mark, Peter A. Szabo, Can Ergen, Daniel P. Caron, Ana Raquel Maceiras, Elior Rahmani, Eli Benuck, Valeh Valiollah Pour Amiri, David Chen, Allon Wagner, Sarah K. Howlett, Lorna B. Jarvis, Karen L. Ellis, Masaru Kubota, Rei Matsumoto, Krishnaa Mahbubani, Kouresh Saeb-Parsy, Cecilia Dominguez Conde, Laura Richardson, Chuan Xu, Shuang Li, Lira Mamanova, Liam Bolt, Alicja Wilk, Sarah A. Teichmann, Donna L. Farber, Peter A. Sims, Joanne L. Jones, Nir Yosef

{"title":"Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age","authors":"Steven B. Wells, Daniel B. Rainbow, Michal Mark, Peter A. Szabo, Can Ergen, Daniel P. Caron, Ana Raquel Maceiras, Elior Rahmani, Eli Benuck, Valeh Valiollah Pour Amiri, David Chen, Allon Wagner, Sarah K. Howlett, Lorna B. Jarvis, Karen L. Ellis, Masaru Kubota, Rei Matsumoto, Krishnaa Mahbubani, Kouresh Saeb-Parsy, Cecilia Dominguez Conde, Laura Richardson, Chuan Xu, Shuang Li, Lira Mamanova, Liam Bolt, Alicja Wilk, Sarah A. Teichmann, Donna L. Farber, Peter A. Sims, Joanne L. Jones, Nir Yosef","doi":"10.1038/s41590-025-02241-4","DOIUrl":"10.1038/s41590-025-02241-4","url":null,"abstract":"The immune system comprises multiple cell lineages and subsets maintained in tissues throughout the lifespan, with unknown effects of tissue and age on immune cell function. Here we comprehensively profiled RNA and surface protein expression of over 1.25 million immune cells from blood and lymphoid and mucosal tissues from 24 organ donors aged 20–75 years. We annotated major lineages (T cells, B cells, innate lymphoid cells and myeloid cells) and corresponding subsets using a multimodal classifier and probabilistic modeling for comparison across tissue sites and age. We identified dominant site-specific effects on immune cell composition and function across lineages; age-associated effects were manifested by site and lineage for macrophages in mucosal sites, B cells in lymphoid organs, and circulating T cells and natural killer cells across blood and tissues. Our results reveal tissue-specific signatures of immune homeostasis throughout the body, from which to define immune pathologies across the human lifespan. Wells et al. profile RNA and surface protein expression to describe dominant tissue-specific effects on immune cell composition and function across lineages in the human tissues across age.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 9","pages":"1612-1625"},"PeriodicalIF":27.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-025-02241-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825381","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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A unique p52 NF-κB–ETS1 interaction ushers in a new paradigm of germinal center responses 一个独特的p52 NF -κB-ETS1相互作用引入了生发中心反应的新范式

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-12 DOI: 10.1038/s41590-025-02246-z

Lee Ann Garrett-Sinha, Satrajit Sinha

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TNF and type I interferon crosstalk controls the fate and function of plasmacytoid dendritic cells TNF和I型干扰素串扰控制浆细胞样树突状细胞的命运和功能

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-12 DOI: 10.1038/s41590-025-02234-3

Rebeca Arroyo Hornero, Raul A. Maqueda-Alfaro, Miguel A. Solís-Barbosa, Rebecca A. Leylek, Olin Medina Chavez, Olivia M. Martinez, Andres Gottfried-Blackmore, Juliana Idoyaga

{"title":"TNF and type I interferon crosstalk controls the fate and function of plasmacytoid dendritic cells","authors":"Rebeca Arroyo Hornero, Raul A. Maqueda-Alfaro, Miguel A. Solís-Barbosa, Rebecca A. Leylek, Olin Medina Chavez, Olivia M. Martinez, Andres Gottfried-Blackmore, Juliana Idoyaga","doi":"10.1038/s41590-025-02234-3","DOIUrl":"10.1038/s41590-025-02234-3","url":null,"abstract":"Plasmacytoid dendritic cells (pDCs) are major producers of type I interferon (IFN-I), an important antiviral cytokine, and activity of these cells must be tightly controlled to prevent harmful inflammation and autoimmunity. Evidence exists that one regulatory mechanism is a fate-switching process from an IFN-I-secreting pDC to a professional antigen-presenting conventional dendritic cell (cDC) that lacks IFN-I-secreting capacity. However, this differentiation process is controversial owing to limitations in tracking the fate of individual cells over time. Here we use single-cell omics and functional experiments to show that activated human pDCs can lose their identity as IFN-I-secreting cells and acquire the transcriptional, epigenetic and functional features of cDCs. This pDC fate-switching process is promoted by tumor necrosis factor but blocked by IFN-I. Importantly, it occurs in vivo during human skin inflammatory diseases and injury, and physiologically in elderly people. This work identifies the pDC-to-cDC reprogramming trajectory and unveils a mechanistic framework for harnessing it therapeutically. Plasmacytoid dendritic cells are type 1 interferon (IFN-I)-producing antiviral specialists that have been shown to be able to differentiate into conventional dendritic cells. Here the authors show how this differentiation is controlled by tumor necrosis factor driving type 2 conventional dendritic cell-like reprogramming and IFN-I blocking it, a process that occurs during inflammation, injury and aging.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 9","pages":"1540-1552"},"PeriodicalIF":27.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-025-02234-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819145","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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A STUB1–CHIC2 complex inhibits CD8+ T cells to restrain tumor immunity STUB1-CHIC2复合物抑制CD8+ T细胞抑制肿瘤免疫

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-12 DOI: 10.1038/s41590-025-02231-6

Martin W. LaFleur, Lauren E. Milling, Priyamvada Prathima, Vivian Li, Ashlyn M. Lemmen, Ivy S. L. Streeter, Paul K. S. Heisig, Nicole M. Derosia, Elizabeth Riffo, Haonan Xu, Thao H. Nguyen, Aashiya Kolengaden, Samuel C. Markson, John G. Doench, Arlene H. Sharpe

{"title":"A STUB1–CHIC2 complex inhibits CD8+ T cells to restrain tumor immunity","authors":"Martin W. LaFleur, Lauren E. Milling, Priyamvada Prathima, Vivian Li, Ashlyn M. Lemmen, Ivy S. L. Streeter, Paul K. S. Heisig, Nicole M. Derosia, Elizabeth Riffo, Haonan Xu, Thao H. Nguyen, Aashiya Kolengaden, Samuel C. Markson, John G. Doench, Arlene H. Sharpe","doi":"10.1038/s41590-025-02231-6","DOIUrl":"10.1038/s41590-025-02231-6","url":null,"abstract":"In vivo CRISPR screens in CD8+ T cells have previously uncovered targets for cancer immunotherapy; however, a minority of the genome has been individually annotated, suggesting that additional regulators remain to be discovered. Here we assessed 899 genes in CD8+ T cells responding to murine melanoma and identified the E3 ubiquitin ligase STUB1 as a new negative regulator of anti-tumor CD8+ T cell function. We demonstrated that Stub1 knockout CD8+ T cells effectively control tumor growth across multiple murine models. Mechanistically, STUB1 interacts with the adapter protein CHIC2 to regulate cytokine receptor expression in mouse and human CD8+ T cells. Among the regulated cytokine receptors, interleukin-27 receptor α is essential for tumor growth control mediated by Stub1/Chic2 knockout CD8+ T cells. Together, these findings establish the STUB1–CHIC2 complex as a regulator of cytokine receptor expression in CD8+ T cells and provide rationale for inhibiting this pathway to enhance CD8+ T cell-mediated anti-tumor immunity. LaFleur, Milling et al. perform an in vivo CRISPR screen of CD8+ T cells responding to tumors. They identify the E3 ubiquitin ligase STUB1 as a potent negative regulator of CD8+ T cell responses in tumors.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 9","pages":"1476-1487"},"PeriodicalIF":27.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819146","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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T cells fast-track gut signals to the brain T细胞将肠道信号快速传递到大脑

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-11 DOI: 10.1038/s41590-025-02237-0

Emanuela Pasciuto, Adrian Liston

引用次数: 0

TCF19 drives a broad transcriptional program that potentiates optimal innate and adaptive functions of antiviral NK cells TCF19驱动广泛的转录程序，增强抗病毒NK细胞的最佳先天和适应性功能

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-08 DOI: 10.1038/s41590-025-02238-z

Celeste Dang, Hyunu Kim, Endi K. Santosa, Rebecca B. Delconte, Alexander H. Settle, Morgan Huse, Joseph C. Sun

{"title":"TCF19 drives a broad transcriptional program that potentiates optimal innate and adaptive functions of antiviral NK cells","authors":"Celeste Dang, Hyunu Kim, Endi K. Santosa, Rebecca B. Delconte, Alexander H. Settle, Morgan Huse, Joseph C. Sun","doi":"10.1038/s41590-025-02238-z","DOIUrl":"10.1038/s41590-025-02238-z","url":null,"abstract":"Natural killer (NK) cells are innate lymphocytes that play a critical role in host defense against viral infection. In addition to rapid effector cytokine production and direct cytotoxicity, NK cells exhibit features of adaptive immunity, including the capacity to undergo robust antigen-specific clonal proliferation and to generate immunological memory1–3. However, the transcriptional programs and regulators governing dynamic NK cell responses to viral infection have not been fully uncovered. In this study, we identified transcription factor 19 (TCF19) as a key driver of NK cell proliferation and calcium signaling in the context of mouse cytomegalovirus infection. Ablation of TCF19 was detrimental to NK cell clonal expansion and host protection against viral infection. Tcf19−/− NK cells were also unable to properly mobilize calcium downstream of antigen signaling to mediate cytotoxicity. Altogether, we find that TCF19 drives a transcriptional program that coordinates the innate and adaptive NK cell responses against viral infection. Sun and colleagues report that the transcription factor TCF19 regulates calcium signaling and cell cycling progression in NK cells and is required for innate and adaptive NK cell responses to viral infection.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 9","pages":"1467-1475"},"PeriodicalIF":27.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796952","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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Author Correction: LARP4-mediated hypertranslation drives T cell dysfunction in tumors 作者更正：larp4介导的超翻译驱动肿瘤中的T细胞功能障碍。

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-08-04 DOI: 10.1038/s41590-025-02260-1

Yi Liu, Haochen Ni, Jie Li, Jing Yang, Ivann Sekielyk, Bryan E. Snow, Zihao Zhang, Feifan Zhang, Michael St. Paul, Jinyi Han, Meghan Kates, Shaofeng Liu, Yawei Zhang, Zurui Huang, Yin Xu, Samuel D. Saibil, Tak W. Mak, Dali Han, Meng Michelle Xu

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Six degrees of TGFβ 6度TGFβ

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02201-y

Quinn Peters, Martin Prlic

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Restoring balanced HSC youth 恢复平衡的HSC青春

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02250-3

Laurie A. Dempsey

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