Nature Immunology最新文献_第7页

MrgprA3 neurons drive cutaneous immunity against helminths through selective control of myeloid-derived IL-33 MrgprA3神经元通过选择性控制髓源性IL-33驱动皮肤对蠕虫的免疫力

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-10-01 DOI: 10.1038/s41590-024-01982-y

Juan M. Inclan-Rico, Camila M. Napuri, Cailu Lin, Li-Yin Hung, Annabel A. Ferguson, Xiaohong Liu, Qinxue Wu, Christopher F. Pastore, Adriana Stephenson, Ulrich M. Femoe, Fungai Musaigwa, Heather L. Rossi, Bruce D. Freedman, Danielle R. Reed, Tomáš Macháček, Petr Horák, Ishmail Abdus-Saboor, Wenqin Luo, De’Broski R. Herbert

{"title":"MrgprA3 neurons drive cutaneous immunity against helminths through selective control of myeloid-derived IL-33","authors":"Juan M. Inclan-Rico, Camila M. Napuri, Cailu Lin, Li-Yin Hung, Annabel A. Ferguson, Xiaohong Liu, Qinxue Wu, Christopher F. Pastore, Adriana Stephenson, Ulrich M. Femoe, Fungai Musaigwa, Heather L. Rossi, Bruce D. Freedman, Danielle R. Reed, Tomáš Macháček, Petr Horák, Ishmail Abdus-Saboor, Wenqin Luo, De’Broski R. Herbert","doi":"10.1038/s41590-024-01982-y","DOIUrl":"10.1038/s41590-024-01982-y","url":null,"abstract":"Skin uses interdependent cellular networks for barrier integrity and host immunity, but most underlying mechanisms remain obscure. Herein, we demonstrate that the human parasitic helminth Schistosoma mansoni inhibited pruritus evoked by itch-sensing afferents bearing the Mas-related G-protein-coupled receptor A3 (MrgprA3) in mice. MrgprA3 neurons controlled interleukin (IL)-17+ γδ T cell expansion, epidermal hyperplasia and host resistance against S. mansoni through shaping cytokine expression in cutaneous antigen-presenting cells. MrgprA3 neuron activation downregulated IL-33 but induced IL-1β and tumor necrosis factor in macrophages and type 2 conventional dendritic cells partially through the neuropeptide calcitonin gene-related peptide. Macrophages exposed to MrgprA3-derived secretions or bearing cell-intrinsic IL-33 deletion showed increased chromatin accessibility at multiple inflammatory cytokine loci, promoting IL-17/IL-23-dependent changes to the epidermis and anti-helminth resistance. This study reveals a previously unrecognized intercellular communication mechanism wherein itch-inducing MrgprA3 neurons initiate host immunity against skin-invasive parasites by directing cytokine expression patterns in myeloid antigen-presenting cell subsets. Herbert and colleagues show MrgprA3+ neurons activate myeloid cells to promote cutaneous IL-17-dependent immunity against Schistosoma mansoni.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"2068-2084"},"PeriodicalIF":27.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330433","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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Inflammatory blood clots 炎性血凝块

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-09-27 DOI: 10.1038/s41590-024-01980-0

Ioana Staicu

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Old and new mpox vaccine 新旧麻疹疫苗

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-09-27 DOI: 10.1038/s41590-024-01979-7

Paula Jauregui

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Editing cancer in vivo 体内编辑癌症

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-09-27 DOI: 10.1038/s41590-024-01978-8

Nicholas J. Bernard

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Learning from inborn errors 从先天错误中学习

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-09-27 DOI: 10.1038/s41590-024-01981-z

Stephanie A. Houston

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Deficiency of metabolic regulator PKM2 activates the pentose phosphate pathway and generates TCF1+ progenitor CD8+ T cells to improve immunotherapy 代谢调节因子 PKM2 的缺乏会激活磷酸戊糖通路并产生 TCF1+ 祖 CD8+ T 细胞，从而改善免疫疗法

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-09-26 DOI: 10.1038/s41590-024-01963-1

Geoffrey J. Markowitz, Yi Ban, Diamile A. Tavarez, Liron Yoffe, Enrique Podaza, Yongfeng He, Mitchell T. Martin, Michael J. P. Crowley, Tito A. Sandoval, Dingcheng Gao, M. Laura Martin, Olivier Elemento, Juan R. Cubillos-Ruiz, Timothy E. McGraw, Nasser K. Altorki, Vivek Mittal

{"title":"Deficiency of metabolic regulator PKM2 activates the pentose phosphate pathway and generates TCF1+ progenitor CD8+ T cells to improve immunotherapy","authors":"Geoffrey J. Markowitz, Yi Ban, Diamile A. Tavarez, Liron Yoffe, Enrique Podaza, Yongfeng He, Mitchell T. Martin, Michael J. P. Crowley, Tito A. Sandoval, Dingcheng Gao, M. Laura Martin, Olivier Elemento, Juan R. Cubillos-Ruiz, Timothy E. McGraw, Nasser K. Altorki, Vivek Mittal","doi":"10.1038/s41590-024-01963-1","DOIUrl":"10.1038/s41590-024-01963-1","url":null,"abstract":"TCF1high progenitor CD8+ T cells mediate the efficacy of immunotherapy; however, the mechanisms that govern their generation and maintenance are poorly understood. Here, we show that targeting glycolysis through deletion of pyruvate kinase muscle 2 (PKM2) results in elevated pentose phosphate pathway (PPP) activity, leading to enrichment of a TCF1high progenitor-exhausted-like phenotype and increased responsiveness to PD-1 blockade in vivo. PKM2KO CD8+ T cells showed reduced glycolytic flux, accumulation of glycolytic intermediates and PPP metabolites and increased PPP cycling as determined by 1,2-13C glucose carbon tracing. Small molecule agonism of the PPP without acute glycolytic impairment skewed CD8+ T cells toward a TCF1high population, generated a unique transcriptional landscape and adoptive transfer of agonist-treated CD8+ T cells enhanced tumor control in mice in combination with PD-1 blockade and promoted tumor killing in patient-derived tumor organoids. Our study demonstrates a new metabolic reprogramming that contributes to a progenitor-like T cell state promoting immunotherapy efficacy. TCF1+ progenitor-exhausted CD8+ T cell populations mediate durable antitumor immunity. Upon antigenic stimulation, effector T cells upregulate aerobic glycolysis to support their cytotoxic phenotype. Here, Mittal and colleagues find that loss of metabolic regulator PKM2 enriches for TCF1+ progenitor-exhausted-like cells and improves responsiveness to PD-1 blockade.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 10","pages":"1884-1899"},"PeriodicalIF":27.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321129","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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Recreating immune and epithelial interactions in organoids 在器官组织中再现免疫与上皮的相互作用

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-09-25 DOI: 10.1038/s41590-024-01967-x

Kevin Man, Axel Kallies

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IRF8 defines the epigenetic landscape in postnatal microglia, thereby directing their transcriptome programs IRF8 定义了出生后小胶质细胞的表观遗传景观，从而指导了它们的转录组程序

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-09-23 DOI: 10.1038/s41590-024-01962-2

Keita Saeki, Richard Pan, Eunju Lee, Daisuke Kurotaki, Keiko Ozato

{"title":"IRF8 defines the epigenetic landscape in postnatal microglia, thereby directing their transcriptome programs","authors":"Keita Saeki, Richard Pan, Eunju Lee, Daisuke Kurotaki, Keiko Ozato","doi":"10.1038/s41590-024-01962-2","DOIUrl":"10.1038/s41590-024-01962-2","url":null,"abstract":"Microglia are innate immune cells in the brain. Transcription factor IRF8 (interferon regulatory factor 8) is highly expressed in microglia. However, its role in postnatal microglia development is unknown. We demonstrate that IRF8 binds stepwise to enhancer regions of postnatal microglia along with Sall1 and PU.1, reaching a maximum after day 14. IRF8 binding correlated with a stepwise increase in chromatin accessibility, which preceded the initiation of microglia-specific transcriptome. Constitutive and postnatal Irf8 deletion led to a loss of microglia identity and gain of disease-associated microglia (DAM)-like genes. Combined analysis of single-cell (sc)RNA sequencing and single-cell transposase-accessible chromatin with sequencing (scATAC–seq) revealed a correlation between chromatin accessibility and transcriptome at a single-cell level. IRF8 was also required for microglia-specific DNA methylation patterns. Last, in the 5xFAD model, constitutive and postnatal Irf8 deletion reduced the interaction of microglia with amyloidβ plaques and the size of plaques, lessening neuronal loss. Together, IRF8 sets the epigenetic landscape, which is required for postnatal microglia gene expression. Saeki and colleagues show that IRF8 defines the epigenetic landscape in postnatal microglia, thereby directing their transcriptome programs.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 10","pages":"1928-1942"},"PeriodicalIF":27.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276873","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

IRF8 as durable architect of the microglial chromatin landscape IRF8 是小胶质细胞染色质景观的持久设计师

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-09-23 DOI: 10.1038/s41590-024-01965-z

Maximilian Frosch, Marco Prinz

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Epigenetic tuning of PD-1 expression improves exhausted T cell function and viral control 对 PD-1 表达进行表观遗传学调整可改善衰竭 T 细胞的功能和病毒控制能力

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-09-17 DOI: 10.1038/s41590-024-01961-3

Sarah A. Weiss, Amy Y. Huang, Megan E. Fung, Daniela Martinez, Alex C. Y. Chen, Thomas J. LaSalle, Brian C. Miller, Christopher D. Scharer, Mudra Hegde, Thao H. Nguyen, Jared H. Rowe, Jossef F. Osborn, Dillon G. Patterson, Natalia Sifnugel, C. Mei-An Nolan, Richard A. Davidson, Marc A. Schwartz, Alexander P. R. Bally, Dennis K. Neeld, Martin W. LaFleur, Jeremy M. Boss, John G. Doench, W. Nicholas Haining, Arlene H. Sharpe, Debattama R. Sen

{"title":"Epigenetic tuning of PD-1 expression improves exhausted T cell function and viral control","authors":"Sarah A. Weiss, Amy Y. Huang, Megan E. Fung, Daniela Martinez, Alex C. Y. Chen, Thomas J. LaSalle, Brian C. Miller, Christopher D. Scharer, Mudra Hegde, Thao H. Nguyen, Jared H. Rowe, Jossef F. Osborn, Dillon G. Patterson, Natalia Sifnugel, C. Mei-An Nolan, Richard A. Davidson, Marc A. Schwartz, Alexander P. R. Bally, Dennis K. Neeld, Martin W. LaFleur, Jeremy M. Boss, John G. Doench, W. Nicholas Haining, Arlene H. Sharpe, Debattama R. Sen","doi":"10.1038/s41590-024-01961-3","DOIUrl":"10.1038/s41590-024-01961-3","url":null,"abstract":"PD-1 is a key negative regulator of CD8+ T cell activation and is highly expressed by exhausted T cells in cancer and chronic viral infection. Although PD-1 blockade can improve viral and tumor control, physiological PD-1 expression prevents immunopathology and improves memory formation. The mechanisms driving high PD-1 expression in exhaustion are not well understood and could be critical to disentangling its beneficial and detrimental effects. Here, we functionally interrogated the epigenetic regulation of PD-1 using a mouse model with deletion of an exhaustion-specific PD-1 enhancer. Enhancer deletion exclusively alters PD-1 expression in CD8+ T cells in chronic infection, creating a ‘sweet spot’ of intermediate expression where T cell function is optimized compared to wild-type and Pdcd1-knockout cells. This permits improved control of chronic infection without additional immunopathology. Together, these results demonstrate that tuning PD-1 via epigenetic editing can reduce CD8+ T cell dysfunction while avoiding excess immunopathology. PD-1 is a critical modulator of CD8+ T cell activation and exhaustion. Sen and colleagues show that a cell-state-specific enhancer tunes PD-1 expression exclusively in exhaustion and that deletion of this enhancer improves CD8+ T cell function.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 10","pages":"1871-1883"},"PeriodicalIF":27.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142235043","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