Nature Immunology最新文献

{"title":"A mutant BCL11B-N440K protein interferes with BCL11A function during T lymphocyte and neuronal development","authors":"Kazuki Okuyama, Motoi Yamashita, Artemis Koumoundourou, Christoph Wiegreffe, Michiko Ohno-Oishi, Samuel J. H. Murphy, Xin Zhao, Hideyuki Yoshida, Takashi Ebihara, Naoko Satoh-Takayama, Satoshi Kojo, Hiroshi Ohno, Tomohiro Morio, Yibo Wu, Jennifer Puck, Hai-Hui Xue, Stefan Britsch, Ichiro Taniuchi","doi":"10.1038/s41590-024-01997-5","DOIUrl":"10.1038/s41590-024-01997-5","url":null,"abstract":"Genetic studies in mice have shown that the zinc finger transcription factor BCL11B has an essential role in regulating early T cell development and neurogenesis. A de novo heterozygous missense BCL11B variant, BCL11BN441K, was isolated from a patient with T cell deficiency and neurological disorders. Here, we show that mice harboring the corresponding Bcl11bN440K mutation show the emergence of natural killer (NK)/group 1 innate lymphoid cell (ILC1)-like NKp46+ cells in the thymus and reduction in TBR1+ neurons in the neocortex, which are observed with loss of Bcl11a but not Bcl11b. Thus, the mutant BCL11B-N440K protein interferes with BCL11A function upon heterodimerization. Mechanistically, the Bcl11bN440K mutation dampens the interaction of BCL11B with T cell factor 1 (TCF1) in thymocytes, resulting in weakened antagonism against TCF1 activity that supports the differentiation of NK/ILC1-like cells. Collectively, our results shed new light on the function of BCL11A in suppressing non-T lymphoid developmental potential and uncover the pathogenic mechanism by which BCL11B-N440K interferes with partner BCL11 family proteins. Taniuchi and colleagues describe the generation and phenotype of a mouse model carrying a defective Bcl11b allele encoding a mutant protein corresponding to BCL11B-N441K previously associated with human disease. They further characterize the molecular interactions between the mutant BCL11B protein and other transcription factors involved in early thymocyte development.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 12","pages":"2284-2296"},"PeriodicalIF":27.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562149","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":"Dosage compensation in T cells","authors":"Laurie A. Dempsey","doi":"10.1038/s41590-024-02012-7","DOIUrl":"10.1038/s41590-024-02012-7","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"1979-1979"},"PeriodicalIF":27.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519567","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":"Innate memory against viruses","authors":"Paula Jauregui","doi":"10.1038/s41590-024-02009-2","DOIUrl":"10.1038/s41590-024-02009-2","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"1979-1979"},"PeriodicalIF":27.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519572","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":"IL-1α in aging tumors","authors":"Stephanie Houston","doi":"10.1038/s41590-024-02013-6","DOIUrl":"10.1038/s41590-024-02013-6","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"1979-1979"},"PeriodicalIF":27.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519612","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":"How to feed mitochondria to T cells","authors":"Nicholas J. Bernard","doi":"10.1038/s41590-024-02008-3","DOIUrl":"10.1038/s41590-024-02008-3","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"1979-1979"},"PeriodicalIF":27.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519569","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":"Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma","authors":"Daniel H. Shu, Won Jin Ho, Luciane T. Kagohara, Alexander Girgis, Sarah M. Shin, Ludmila Danilova, Jae W. Lee, Dimitrios N. Sidiropoulos, Sarah Mitchell, Kabeer Munjal, Kathryn Howe, Kayla J. Bendinelli, Emma Kartalia, Hanfei Qi, Guanglan Mo, Janelle Montagne, James M. Leatherman, Tamara Y. Lopez-Vidal, Qingfeng Zhu, Amanda L. Huff, Xuan Yuan, Alexei Hernandez, Erin M. Coyne, Neeha Zaidi, Daniel J. Zabransky, Logan L. Engle, Aleksandra Ogurtsova, Marina Baretti, Daniel Laheru, Jennifer N. Durham, Hao Wang, Joel C. Sunshine, Robert J. Johnston, Julie Stein Deutsch, Janis M. Taube, Robert A. Anders, Elizabeth M. Jaffee, Elana J. Fertig, Mark Yarchoan","doi":"10.1038/s41590-024-01992-w","DOIUrl":"10.1038/s41590-024-01992-w","url":null,"abstract":"Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade, but understanding of the prognostic and predictive value of TLS and the circumstances of their resolution is incomplete. Here we show that in hepatocellular carcinoma treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse-free survival. In areas of tumor regression, we identify a noncanonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell–mature dendritic cell interactions and increased expression of T cell memory markers. Collectively, these data suggest that TLS can serve as both a prognostic and predictive marker of response to immunotherapy in hepatocellular carcinoma and that late-stage TLS may support T cell memory formation after elimination of a viable tumor. Here the authors functionally characterize hepatocellular carcinoma associated tertiary lymphoid structures (TLS) in patients treated with neoadjuvant immunotherapy and present further evidence for using these TLS as a biomarker of response to therapy.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"2110-2123"},"PeriodicalIF":27.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489214","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":"Involuted TLS as a harbinger of HCC regression","authors":"Xin Liu, Dan G. Duda","doi":"10.1038/s41590-024-01990-y","DOIUrl":"10.1038/s41590-024-01990-y","url":null,"abstract":"Tertiary lymphoid structures (TLS) have different stages and cellular compositions in human tumors. New data are showing the effect of neoadjuvant immunotherapy on the fate of TLS in treatment-responsive versus treatment-resistant liver cancers.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"1986-1987"},"PeriodicalIF":27.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489212","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":"A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease","authors":"Tom Thomas, Matthias Friedrich, Charlotte Rich-Griffin, Mathilde Pohin, Devika Agarwal, Julia Pakpoor, Carl Lee, Ruchi Tandon, Aniko Rendek, Dominik Aschenbrenner, Ashwin Jainarayanan, Alexandru Voda, Jacqueline H. Y. Siu, Raphael Sanches-Peres, Eloise Nee, Dharshan Sathananthan, Dylan Kotliar, Peter Todd, Maria Kiourlappou, Lisa Gartner, Nicholas Ilott, Fadi Issa, Joanna Hester, Jason Turner, Saba Nayar, Jonas Mackerodt, Fan Zhang, Anna Jonsson, Michael Brenner, Soumya Raychaudhuri, Ruth Kulicke, Danielle Ramsdell, Nicolas Stransky, Ray Pagliarini, Piotr Bielecki, Noah Spies, Brian Marsden, Stephen Taylor, Allon Wagner, Paul Klenerman, Alissa Walsh, Mark Coles, Luke Jostins-Dean, Fiona M. Powrie, Andrew Filer, Simon Travis, Holm H. Uhlig, Calliope A. Dendrou, Christopher D. Buckley","doi":"10.1038/s41590-024-01994-8","DOIUrl":"10.1038/s41590-024-01994-8","url":null,"abstract":"Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn’s disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases. In this Resource, Buckley and colleagues profile patients with Crohn’s disease and ulcerative colitis before and after adalimumab therapy. Specific pretreatment differences in the epithelial and myeloid compartments were associated with remission outcomes in both diseases. The authors also describe the cellular circuitry in nonremission patients following treatment.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"2152-2165"},"PeriodicalIF":27.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01994-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452631","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":"A SIRT7-dependent acetylation switch regulates early B cell differentiation and lineage commitment through Pax5","authors":"Andres Gamez-Garcia, Maria Espinosa-Alcantud, Alberto Bueno-Costa, Elisenda Alari-Pahissa, Anna Marazuela-Duque, Joshua K. Thackray, Chandni Ray, Clara Berenguer, Poonam Kumari, Joan Josep Bech, Thomas Braun, Alessandro Ianni, Jay A. Tischfield, Lourdes Serrano, Manel Esteller, Jose L. Sardina, Carolina De La Torre, Mikael Sigvardsson, Berta N. Vazquez, Alejandro Vaquero","doi":"10.1038/s41590-024-01995-7","DOIUrl":"10.1038/s41590-024-01995-7","url":null,"abstract":"B lymphopoiesis is orchestrated by lineage-specific transcription factors. In B cell progenitors, lineage commitment is mediated by Pax5, which is commonly mutated in B cell acute lymphoblastic leukemia. Despite its essential role in immunity, the mechanisms regulating Pax5 function remain largely unknown. Here, we found that the NAD+-dependent enzyme SIRT7 coordinates B cell development through deacetylation of Pax5 at K198, which promotes Pax5 protein stability and transcriptional activity. Neither Pax5K198 deacetylated nor acetylated mimics rescued B cell differentiation in Pax5−/− pro-B cells, suggesting that B cell development requires Pax5 dynamic deacetylation. The Pax5K198 deacetylation mimic restored lineage commitment in Pax5−/− pro-B cells and B cell differentiation in Sirt7−/− pro-B cells, suggesting the uncoupling of differentiation from lineage commitment. The SIRT7–Pax5 interplay was conserved in B cell acute lymphoblastic leukemia, where SIRT7 expression correlated with good prognosis. Our findings reveal a crucial mechanism for B lymphopoiesis and highlight the relevance of sirtuins in immune function. Gámez-García et al. show that the deacetylase SIRT7 modulates the acetylation of Pax5 and its ability to repress alternate lineage programs and promote B cell differentiation and commitment in B cell progenitor cells.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 12","pages":"2308-2319"},"PeriodicalIF":27.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01995-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448109","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":"Metabolic–epigenetic rewiring in CD8+ T cells via lactate-dependent histone lactylation","authors":"Renqiang Sun, Hongbo Chi","doi":"10.1038/s41590-024-01991-x","DOIUrl":"10.1038/s41590-024-01991-x","url":null,"abstract":"The interplay of metabolites with epigenetic programs influences CD8+ T cell fate decisions. Here, Raychaudhuri et al. show that lactate-dependent histone lactylation tunes CD8+ T cell metabolism and function by regulating epigenetic and transcriptional remodeling.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"1980-1982"},"PeriodicalIF":27.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440208","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}