Nature Immunology最新文献_第5页

Long-term antiretroviral therapy rejuvenates the HIV-specific CD8+ T cell response 长期抗逆转录病毒疗法使艾滋病毒特异性 CD8+ T 细胞反应恢复活力

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-23 DOI: 10.1038/s41590-024-01924-8

Joel N. Blankson

引用次数: 0

Clonal succession after prolonged antiretroviral therapy rejuvenates CD8+ T cell responses against HIV-1 长期抗逆转录病毒疗法后的克隆继承可使 CD8+ T 细胞对 HIV-1 的反应恢复活力

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-23 DOI: 10.1038/s41590-024-01931-9

Eoghann White, Laura Papagno, Assia Samri, Kenji Sugata, Boris Hejblum, Amy R. Henry, Daniel C. Rogan, Samuel Darko, Patricia Recordon-Pinson, Yasmine Dudoit, Sian Llewellyn-Lacey, Lisa A. Chakrabarti, Florence Buseyne, Stephen A. Migueles, David A. Price, Marie-Aline Andreola, Yorifumi Satou, Rodolphe Thiebaut, Christine Katlama, Brigitte Autran, Daniel C. Douek, Victor Appay

{"title":"Clonal succession after prolonged antiretroviral therapy rejuvenates CD8+ T cell responses against HIV-1","authors":"Eoghann White, Laura Papagno, Assia Samri, Kenji Sugata, Boris Hejblum, Amy R. Henry, Daniel C. Rogan, Samuel Darko, Patricia Recordon-Pinson, Yasmine Dudoit, Sian Llewellyn-Lacey, Lisa A. Chakrabarti, Florence Buseyne, Stephen A. Migueles, David A. Price, Marie-Aline Andreola, Yorifumi Satou, Rodolphe Thiebaut, Christine Katlama, Brigitte Autran, Daniel C. Douek, Victor Appay","doi":"10.1038/s41590-024-01931-9","DOIUrl":"10.1038/s41590-024-01931-9","url":null,"abstract":"Human immunodeficiency virus 1 (HIV-1) infection is characterized by a dynamic and persistent state of viral replication that overwhelms the host immune system in the absence of antiretroviral therapy (ART). The impact of prolonged treatment on the antiviral efficacy of HIV-1-specific CD8+ T cells has nonetheless remained unknown. Here, we used single-cell technologies to address this issue in a cohort of aging individuals infected early during the pandemic and subsequently treated with continuous ART. Our data showed that long-term ART was associated with a process of clonal succession, which effectively rejuvenated HIV-1-specific CD8+ T cell populations in the face of immune senescence. Tracking individual transcriptomes further revealed that initially dominant CD8+ T cell clonotypes displayed signatures of exhaustion and terminal differentiation, whereas newly dominant CD8+ T cell clonotypes displayed signatures of early differentiation and stemness associated with natural control of viral replication. These findings reveal a degree of immune resilience that could inform adjunctive treatments for HIV-1. Appay and colleagues show that long-term antiretroviral therapy is associated with clonal succession of HIV-1-specific CD8+ T cell populations, which evolved from an exhaustion-like toward a stemness-like phenotype.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042701","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

Transcriptional function of E2A, Ebf1, Pax5, Ikaros and Aiolos analyzed by in vivo acute protein degradation in early B cell development 通过体内急性蛋白降解分析早期 B 细胞发育过程中 E2A、Ebf1、Pax5、Ikaros 和 Aiolos 的转录功能

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-23 DOI: 10.1038/s41590-024-01933-7

Anna S. Fedl, Hiromi Tagoh, Sarah Gruenbacher, Qiong Sun, Robyn L. Schenk, Kimon Froussios, Markus Jaritz, Meinrad Busslinger, Tanja A. Schwickert

{"title":"Transcriptional function of E2A, Ebf1, Pax5, Ikaros and Aiolos analyzed by in vivo acute protein degradation in early B cell development","authors":"Anna S. Fedl, Hiromi Tagoh, Sarah Gruenbacher, Qiong Sun, Robyn L. Schenk, Kimon Froussios, Markus Jaritz, Meinrad Busslinger, Tanja A. Schwickert","doi":"10.1038/s41590-024-01933-7","DOIUrl":"10.1038/s41590-024-01933-7","url":null,"abstract":"Early B cell lymphopoiesis depends on E2A, Ebf1, Pax5 and Ikaros family members. In the present study, we used acute protein degradation in mice to identify direct target genes of these transcription factors in pro-B, small pre-B and immature B cells. E2A, Ebf1 and Pax5 predominantly function as transcriptional activators by inducing open chromatin at their target genes, have largely unique functions and are essential for early B cell maintenance. Ikaros and Aiolos act as dedicated repressors to cooperatively control early B cell development. The surrogate light-chain genes Igll1 and Vpreb1 are directly activated by Ebf1 and Pax5 in pro-B cells and directly repressed by Ikaros and Aiolos in small pre-B cells. Pax5 and E2A contribute to V(D)J recombination by activating Rag1, Rag2, Dntt, Irf4 and Irf8. Similar to Pax5, Ebf1 also represses the cohesin-release factor gene Wapl to mediate prolonged loop extrusion across the Igh locus. In summary, in vivo protein degradation has provided unprecedented insight into the control of early B cell lymphopoiesis by five transcription factors. By use of a degron-mediated acute protein degradation model, Schwickert and colleagues are able to distinguish between direct and indirect gene targets of multiple transcription factors involved in early B cell development.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042703","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

Mapping spatial organization and genetic cell-state regulators to target immune evasion in ovarian cancer 绘制空间组织和遗传细胞状态调节因子图，以卵巢癌中的免疫逃避为目标

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-23 DOI: 10.1038/s41590-024-01943-5

Christine Yiwen Yeh, Karmen Aguirre, Olivia Laveroni, Subin Kim, Aihui Wang, Brooke Liang, Xiaoming Zhang, Lucy M. Han, Raeline Valbuena, Michael C. Bassik, Young-Min Kim, Sylvia K. Plevritis, Michael P. Snyder, Brooke E. Howitt, Livnat Jerby

{"title":"Mapping spatial organization and genetic cell-state regulators to target immune evasion in ovarian cancer","authors":"Christine Yiwen Yeh, Karmen Aguirre, Olivia Laveroni, Subin Kim, Aihui Wang, Brooke Liang, Xiaoming Zhang, Lucy M. Han, Raeline Valbuena, Michael C. Bassik, Young-Min Kim, Sylvia K. Plevritis, Michael P. Snyder, Brooke E. Howitt, Livnat Jerby","doi":"10.1038/s41590-024-01943-5","DOIUrl":"10.1038/s41590-024-01943-5","url":null,"abstract":"The drivers of immune evasion are not entirely clear, limiting the success of cancer immunotherapies. Here we applied single-cell spatial and perturbational transcriptomics to delineate immune evasion in high-grade serous tubo-ovarian cancer. To this end, we first mapped the spatial organization of high-grade serous tubo-ovarian cancer by profiling more than 2.5 million cells in situ in 130 tumors from 94 patients. This revealed a malignant cell state that reflects tumor genetics and is predictive of T cell and natural killer cell infiltration levels and response to immune checkpoint blockade. We then performed Perturb-seq screens and identified genetic perturbations—including knockout of PTPN1 and ACTR8—that trigger this malignant cell state. Finally, we show that these perturbations, as well as a PTPN1/PTPN2 inhibitor, sensitize ovarian cancer cells to T cell and natural killer cell cytotoxicity, as predicted. This study thus identifies ways to study and target immune evasion by linking genetic variation, cell-state regulators and spatial biology. Here the authors provide a resource for ovarian cancer combining spatial transcriptomics, genomics, CRISPR Perturb-seq screens and in silico methods to focus on T cells and natural killer cells in the tumor and their role in immune evasion.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01943-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042702","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}

引用次数: 0

Mechanism for controlled assembly of transcriptional condensates by Aire 艾尔转录凝聚体的受控组装机制

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-21 DOI: 10.1038/s41590-024-01922-w

Yu-San Huoh, Qianxia Zhang, Ricarda Törner, Sylvan C. Baca, Haribabu Arthanari, Sun Hur

{"title":"Mechanism for controlled assembly of transcriptional condensates by Aire","authors":"Yu-San Huoh, Qianxia Zhang, Ricarda Törner, Sylvan C. Baca, Haribabu Arthanari, Sun Hur","doi":"10.1038/s41590-024-01922-w","DOIUrl":"10.1038/s41590-024-01922-w","url":null,"abstract":"Transcriptional condensates play a crucial role in gene expression and regulation, yet their assembly mechanisms remain poorly understood. Here, we report a multi-layered mechanism for condensate assembly by autoimmune regulator (Aire), an essential transcriptional regulator that orchestrates gene expression reprogramming for central T cell tolerance. Aire condensates assemble on enhancers, stimulating local transcriptional activities and connecting disparate inter-chromosomal loci. This functional condensate formation hinges upon the coordination between three Aire domains: polymerization domain caspase activation recruitment domain (CARD), histone-binding domain (first plant homeodomain (PHD1)), and C-terminal tail (CTT). Specifically, CTT binds coactivators CBP/p300, recruiting Aire to CBP/p300-rich enhancers and promoting CARD-mediated condensate assembly. Conversely, PHD1 binds to the ubiquitous histone mark H3K4me0, keeping Aire dispersed throughout the genome until Aire nucleates on enhancers. Our findings showed that the balance between PHD1-mediated suppression and CTT-mediated stimulation of Aire polymerization is crucial to form transcriptionally active condensates at target sites, providing new insights into controlled polymerization of transcriptional regulators. Sun Hur and colleagues examine the mechanism of Aire protein function underlying peripheral tissue antigen gene expression in thymic mTECs. They show that Aire condensates assemble on enhancers that are subject to intricate regulatory mechanisms, ensuring tight coordination of Aire CARD polymerization with genomic target recognition.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01922-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013805","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}

引用次数: 0

Tumor editing suppresses innate and adaptive antitumor immunity and is reversed by inhibiting DNA methylation 肿瘤编辑会抑制先天性和适应性抗肿瘤免疫，而抑制 DNA 甲基化则可逆转这种情况

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-21 DOI: 10.1038/s41590-024-01932-8

Ying Zhang, Pourya Naderi Yeganeh, Haiwei Zhang, Simon Yuan Wang, Zhouyihan Li, Bowen Gu, Dian-Jang Lee, Zhibin Zhang, Athanasios Ploumakis, Ming Shi, Hao Wu, Eric Lieberman Greer, Winston Hide, Judy Lieberman

{"title":"Tumor editing suppresses innate and adaptive antitumor immunity and is reversed by inhibiting DNA methylation","authors":"Ying Zhang, Pourya Naderi Yeganeh, Haiwei Zhang, Simon Yuan Wang, Zhouyihan Li, Bowen Gu, Dian-Jang Lee, Zhibin Zhang, Athanasios Ploumakis, Ming Shi, Hao Wu, Eric Lieberman Greer, Winston Hide, Judy Lieberman","doi":"10.1038/s41590-024-01932-8","DOIUrl":"10.1038/s41590-024-01932-8","url":null,"abstract":"Cancer cells edit gene expression to evade immunosurveillance. However, genome-wide studies of gene editing during early tumorigenesis are lacking. Here we used single-cell RNA sequencing in a breast cancer genetically engineered mouse model (GEMM) to identify edited genes without bias. Late tumors repressed antitumor immunity genes, reducing infiltrating immune cells and tumor–immune cell communications. Innate immune genes, especially interferon-stimulated genes, dominated the list of downregulated tumor genes, while genes that regulate cell-intrinsic malignancy were mostly unedited. Naive and activated CD8+ T cells in early tumors were replaced with exhausted or precursor-exhausted cells in late tumors. Repression of immune genes was reversed by inhibiting DNA methylation using low-dose decitabine, which suppressed tumor growth and restored immune control, increasing the number, functionality and memory of tumor-infiltrating lymphocytes and reducing the number of myeloid suppressor cells. Decitabine induced important interferon, pyroptosis and necroptosis genes, inflammatory cell death and immune control in GEMM and implanted breast and melanoma tumors. Tumor immunoediting occurs early during tumorigenesis and is thereby difficult to study. Here the authors overcome this issue using an aggressive breast cancer model that enables them to compare and contrast the trancriptomic state of early versus late tumors.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013856","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

Phenotype and specificity of lung T cell responses correlate with outcome in SARS-CoV-2 pneumonia 肺 T 细胞反应的表型和特异性与 SARS-CoV-2 肺炎的预后有关

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-21 DOI: 10.1038/s41590-024-01941-7

引用次数: 0

A balancing act in the control of self-antigen expression 自我抗原表达控制中的平衡行为

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-21 DOI: 10.1038/s41590-024-01940-8

Michael R. Waterfield, Mark S. Anderson

引用次数: 0

Influenza vaccination stimulates maturation of the human T follicular helper cell response 流感疫苗接种刺激人类 T 滤泡辅助细胞反应的成熟

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-20 DOI: 10.1038/s41590-024-01926-6

Stefan A. Schattgen, Jackson S. Turner, Mohamed A. Ghonim, Jeremy Chase Crawford, Aaron J. Schmitz, Hyunjin Kim, Julian Q. Zhou, Walid Awad, Robert C. Mettelman, Wooseob Kim, Katherine M. McIntire, Alem Haile, Michael K. Klebert, Teresa Suessen, William D. Middleton, Sharlene A. Teefey, Rachel M. Presti, Ali H. Ellebedy, Paul G. Thomas

{"title":"Influenza vaccination stimulates maturation of the human T follicular helper cell response","authors":"Stefan A. Schattgen, Jackson S. Turner, Mohamed A. Ghonim, Jeremy Chase Crawford, Aaron J. Schmitz, Hyunjin Kim, Julian Q. Zhou, Walid Awad, Robert C. Mettelman, Wooseob Kim, Katherine M. McIntire, Alem Haile, Michael K. Klebert, Teresa Suessen, William D. Middleton, Sharlene A. Teefey, Rachel M. Presti, Ali H. Ellebedy, Paul G. Thomas","doi":"10.1038/s41590-024-01926-6","DOIUrl":"10.1038/s41590-024-01926-6","url":null,"abstract":"The differentiation and specificity of human CD4+ T follicular helper cells (TFH cells) after influenza vaccination have been poorly defined. Here we profiled blood and draining lymph node (LN) samples from human volunteers for over 2 years after two influenza vaccines were administered 1 year apart to define the evolution of the CD4+ TFH cell response. The first vaccination induced an increase in the frequency of circulating TFH (cTFH) and LN TFH cells at week 1 postvaccination. This increase was transient for cTFH cells, whereas the LN TFH cells further expanded during week 2 and remained elevated in frequency for at least 3 months. We observed several distinct subsets of TFH cells in the LN, including pre-TFH cells, memory TFH cells, germinal center (GC) TFH cells and interleukin-10+ TFH cell subsets beginning at baseline and at all time points postvaccination. The shift toward a GC TFH cell phenotype occurred with faster kinetics after the second vaccine compared to the first vaccine. We identified several influenza-specific TFH cell clonal lineages, including multiple responses targeting internal influenza virus proteins, and found that each TFH cell state was attainable within a clonal lineage. Thus, human TFH cells form a durable and dynamic multitissue network. Schattgen et al. profiled the subsets and clonality of CD4+ TFH cells in the blood and lymph nodes of human volunteers who received two influenza vaccines 1 year apart to characterize their dynamics and clonal evolution over 2 years.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01926-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007484","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}

引用次数: 0

TFH cell responses endure in human lymph nodes after vaccination 接种疫苗后，人体淋巴结中的 TFH 细胞反应持续存在

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-20 DOI: 10.1038/s41590-024-01935-5

Cody S. Nelson, Peter T. Sage

引用次数: 0