Nature Immunology最新文献

{"title":"Author Correction: Sepsis-trained macrophages promote antitumoral tissue-resident T cells","authors":"Alexis Broquet, Victor Gourain, Thomas Goronflot, Virginie Le Mabecque, Debajyoti Sinha, Mitra Ashayeripanah, Cédric Jacqueline, Pierre Martin, Marion Davieau, Lea Boutin, Cecile Poulain, Florian P. Martin, Cynthia Fourgeux, Melanie Petrier, Manon Cannevet, Thomas Leclercq, Maeva Guillonneau, Tanguy Chaumette, Thomas Laurent, Christelle Harly, Emmanuel Scotet, Laurent Legentil, Vincent Ferrières, Stephanie Corgnac, Fathia Mami-Chouaib, Jean Francois Mosnier, Nicolas Mauduit, Hamish E. G. McWilliam, Jose A. Villadangos, Pierre Antoine Gourraud, Karim Asehnoune, Jeremie Poschmann, Antoine Roquilly","doi":"10.1038/s41590-024-02000-x","DOIUrl":"10.1038/s41590-024-02000-x","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"2167-2167"},"PeriodicalIF":27.7,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-02000-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383645","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}

{"title":"Histone lactylation drives CD8+ T cell metabolism and function","authors":"Deblina Raychaudhuri, Pratishtha Singh, Bidisha Chakraborty, Mercedes Hennessey, Aminah J. Tannir, Shrinidhi Byregowda, Seanu Meena Natarajan, Abel Trujillo-Ocampo, Jin Seon Im, Sangeeta Goswami","doi":"10.1038/s41590-024-01985-9","DOIUrl":"10.1038/s41590-024-01985-9","url":null,"abstract":"The activation and functional differentiation of CD8+ T cells are linked to metabolic pathways that result in the production of lactate. Lactylation is a lactate-derived histone post-translational modification; however, the relevance of histone lactylation in the context of CD8+ T cell activation and function is not known. Here, we show the enrichment of H3K18 lactylation (H3K18la) and H3K9 lactylation (H3K9la) in human and mouse CD8+ T cells, which act as transcription initiators of key genes regulating CD8+ T cell function. Further, we note distinct patterns of H3K18la and H3K9la in CD8+ T cell subsets linked to their specific metabolic profiles. Additionally, we find that modulation of H3K18la and H3K9la by targeting metabolic and epigenetic pathways influence CD8+ T cell effector function, including antitumor immunity, in preclinical models. Overall, our study uncovers the potential roles of H3K18la and H3K9la in CD8+ T cells. Goswami and colleagues describe how lactylation of histone lysine residues regulates the transcriptome, metabolism and function of CD8+ T cells.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"2140-2151"},"PeriodicalIF":27.7,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383647","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}

{"title":"Author Correction: GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunit","authors":"Jiaxian Yan, Chi Zhang, Yueli Xu, Zonghui Huang, Qingyuan Ye, Xiaojun Qian, Liang Zhu, Guangming Huang, Xiaqiong Wang, Wei Jiang, Rongbin Zhou","doi":"10.1038/s41590-024-02001-w","DOIUrl":"10.1038/s41590-024-02001-w","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"2167-2167"},"PeriodicalIF":27.7,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-02001-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383646","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}

{"title":"Optimization of the Irf8 +32-kb enhancer disrupts dendritic cell lineage segregation","authors":"Feiya Ou, Tian-Tian Liu, Pritesh Desai, Stephen T. Ferris, Sunkyung Kim, Haolin Shen, Ray A. Ohara, Suin Jo, Jing Chen, J. Luke Postoak, Siling Du, Michael S. Diamond, Theresa L. Murphy, Kenneth M. Murphy","doi":"10.1038/s41590-024-01976-w","DOIUrl":"10.1038/s41590-024-01976-w","url":null,"abstract":"Autoactivation of lineage-determining transcription factors mediates bistable expression, generating distinct cell phenotypes essential for complex body plans. Classical type 1 dendritic cell (cDC1) and type 2 dendritic cell (cDC2) subsets provide nonredundant functions for defense against distinct immune challenges. Interferon regulatory factor 8 (IRF8), the cDC1 lineage-determining transcription factor, undergoes autoactivation in cDC1 progenitors to establish cDC1 identity, yet its expression is downregulated during cDC2 differentiation by an unknown mechanism. This study reveals that the Irf8 +32-kb enhancer, responsible for IRF8 autoactivation, is naturally suboptimized with low-affinity IRF8 binding sites. Introducing multiple high-affinity IRF8 sites into the Irf8 +32-kb enhancer causes a gain-of-function effect, leading to erroneous IRF8 autoactivation in specified cDC2 progenitors, redirecting them toward cDC1 and a novel hybrid DC subset with mixed-lineage phenotypes. Further, this also causes a loss-of-function effect, reducing Irf8 expression in cDC1s. These developmental alterations critically impair both cDC1-dependent and cDC2-dependent arms of immunity. Collectively, our findings underscore the significance of enhancer suboptimization in the developmental segregation of cDCs required for normal immune function. Some enhancers can limit their activities to specific spatial–temporal domains by enhancer suboptimization. Ou et al. find that classical dendritic cell (cDC) development depends on Irf8 suboptimization, which prevents unwanted IRF8 autoactivation in developing cDC2s while maximizing IRF8 expression in developed cDC1s.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"2043-2056"},"PeriodicalIF":27.7,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383648","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}

{"title":"Monocyte-derived macrophages are too much of a good thing in lung fibrosis","authors":"Leif Erik Sander","doi":"10.1038/s41590-024-01989-5","DOIUrl":"10.1038/s41590-024-01989-5","url":null,"abstract":"Acute lung injury elicits a profibrotic wound healing program in monocyte-derived macrophages. Their abundance is associated with pulmonary fibrosis in individuals recovering from COVID-19 pneumonia.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"1983-1985"},"PeriodicalIF":27.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370044","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}

{"title":"DNA-sensing pathways in health, autoinflammatory and autoimmune diseases","authors":"Mingqi Dong, Katherine A. Fitzgerald","doi":"10.1038/s41590-024-01966-y","DOIUrl":"10.1038/s41590-024-01966-y","url":null,"abstract":"Detection of microbial DNA is a primary means of host defense. In mammalian cells, DNA-sensing pathways induce robust anti-microbial responses and initiation of adaptive immunity, leading to the eventual clearance of the infectious agent. However, while conferring the advantage of broad detection capability, the sequence-independent recognition mechanisms of most DNA sensors pose a significant challenge for mammalian cells to maintain ignorance to self-DNA under homeostatic conditions. In this Review, we summarize the fundamentals of DNA-sensing pathways and the intricate regulatory networks that keep these pathways in check. In addition, we describe how regulatory restraints can be defective and underlie human autoinflammatory and autoimmune diseases. Further, we discuss therapies in development that limit inflammation fueled by self-DNA or inappropriate activation of DNA-sensing pathways. In this Review, Fitzgerald and Dong summarize the fundamentals of DNA-sensing pathways in health, autoinflammatory and autoimmune diseases.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"2001-2014"},"PeriodicalIF":27.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370048","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}

{"title":"Profibrotic monocyte-derived alveolar macrophages are expanded in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19","authors":"Joseph I. Bailey, Connor H. Puritz, Karolina J. Senkow, Nikolay S. Markov, Estefani Diaz, Emmy Jonasson, Zhan Yu, Suchitra Swaminathan, Ziyan Lu, Samuel Fenske, Rogan A. Grant, Hiam Abdala-Valencia, Ruben J. Mylvaganam, Amy Ludwig, Janet Miller, R. Ian Cumming, Robert M. Tighe, Kymberly M. Gowdy, Ravi Kalhan, Manu Jain, Ankit Bharat, Chitaru Kurihara, Ruben San Jose Estepar, Raul San Jose Estepar, George R. Washko, Ali Shilatifard, Jacob I. Sznajder, Karen M. Ridge, G. R. Scott Budinger, Rosemary Braun, Alexander V. Misharin, Marc A. Sala","doi":"10.1038/s41590-024-01975-x","DOIUrl":"10.1038/s41590-024-01975-x","url":null,"abstract":"Monocyte-derived alveolar macrophages drive lung injury and fibrosis in murine models and are associated with pulmonary fibrosis in humans. Monocyte-derived alveolar macrophages have been suggested to develop a phenotype that promotes lung repair as injury resolves. We compared single-cell and cytokine profiling of the alveolar space in a cohort of 35 patients with post-acute sequelae of COVID-19 who had persistent respiratory symptoms and abnormalities on a computed tomography scan of the chest that subsequently improved or progressed. The abundance of monocyte-derived alveolar macrophages, their gene expression programs, and the level of the monocyte chemokine CCL2 in bronchoalveolar lavage fluid positively associated with the severity of radiographic fibrosis. Monocyte-derived alveolar macrophages from patients with resolving or progressive fibrosis expressed the same set of profibrotic genes. Our findings argue against a distinct reparative phenotype in monocyte-derived alveolar macrophages, highlighting their utility as a biomarker of failed lung repair and a potential target for therapy. Misharin, Sala and colleagues show that in patients with lung fibrosis after COVID-19, monocyte-derived alveolar macrophages activate an inflammatory and fibrotic program that was similar in patients with either resolving or progressing fibrosis.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"2097-2109"},"PeriodicalIF":27.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01975-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370046","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}

{"title":"AI and immunology as a new research paradigm","authors":"Anupama E. Gururaj, Richard H. Scheuermann, Dawei Lin","doi":"10.1038/s41590-024-01974-y","DOIUrl":"10.1038/s41590-024-01974-y","url":null,"abstract":"The National Institute of Allergy and Infectious Diseases (NIAID) hosted a symposium on ‘AI and Immunology: Exploring Challenges and Opportunities’. The event considered how artificial intelligence (AI) can advance research on the multi-scale, adaptive immune system to improve human health, covering basic research and clinical use cases, data and AI model fundamentals.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"1993-1996"},"PeriodicalIF":27.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370045","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}

{"title":"GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunity","authors":"Jiaxian Yan, Chi Zhang, Yueli Xu, Zonghui Huang, Qingyuan Ye, Xiaojun Qian, Liang Zhu, Guangming Huang, Xiaqiong Wang, Wei Jiang, Rongbin Zhou","doi":"10.1038/s41590-024-01973-z","DOIUrl":"10.1038/s41590-024-01973-z","url":null,"abstract":"Type 1 innate lymphoid cells (ILC1s) are a class of tissue-resident cells with antitumor activity, suggesting its possible role in solid tumor immune surveillance, but it is not clear whether manipulating ILC1s can induce potent antitumor immune responses. Here, we found that G-protein-coupled receptor 34 (GPR34), a receptor for lysophosphatidylserine (LysoPS), was highly expressed on ILC1s but not on conventional natural killer cells in the tumor microenvironment. LysoPS was enriched in the tumor microenvironment and could inhibit ILC1 activation via GPR34. Genetic deletion of LysoPS synthase Abhd16a expression in tumors or Gpr34 expression in ILC1s or antagonizing GPR34 enhanced ILC1 antitumor activity. In individuals with cancer, ABHD16A expression in tumors or GPR34 expression in ILC1s was inversely correlated with the antitumor activity of ILC1s or ILC1-like cells. Thus, our results demonstrate that manipulating ILC1s can induce potent antitumor immunity, and GPR34 is a metabolic immune checkpoint that can be targeted to develop ILC1-based immunotherapy. Zhou and colleagues find that GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunity.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"2057-2067"},"PeriodicalIF":27.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362777","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}

{"title":"Author Correction: Immunological imprinting and risks of influenza B virus infection","authors":"Isaac C. L. Chow, Sook-San Wong","doi":"10.1038/s41590-024-01996-6","DOIUrl":"10.1038/s41590-024-01996-6","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"2166-2166"},"PeriodicalIF":27.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01996-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363101","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}