Immunity最新文献_第6页

Acute suppression of mitochondrial ATP production prevents apoptosis and provides an essential signal for NLRP3 inflammasome activation 急性抑制线粒体 ATP 的产生可防止细胞凋亡，并为 NLRP3 炎症小体的激活提供重要信号

IF 32.4 1区医学

Immunity Pub Date : 2024-11-20 DOI: 10.1016/j.immuni.2024.10.012

Benedikt S. Saller, Svenja Wöhrle, Larissa Fischer, Clara Dufossez, Isabella L. Ingerl, Susanne Kessler, Maria Mateo-Tortola, Oliver Gorka, Felix Lange, Yurong Cheng, Emilia Neuwirt, Adinarayana Marada, Christoph Koentges, Chiara Urban, Philipp Aktories, Peter Reuther, Sebastian Giese, Susanne Kirschnek, Carolin Mayer, Johannes Pilic, Olaf Groß

{"title":"Acute suppression of mitochondrial ATP production prevents apoptosis and provides an essential signal for NLRP3 inflammasome activation","authors":"Benedikt S. Saller, Svenja Wöhrle, Larissa Fischer, Clara Dufossez, Isabella L. Ingerl, Susanne Kessler, Maria Mateo-Tortola, Oliver Gorka, Felix Lange, Yurong Cheng, Emilia Neuwirt, Adinarayana Marada, Christoph Koentges, Chiara Urban, Philipp Aktories, Peter Reuther, Sebastian Giese, Susanne Kirschnek, Carolin Mayer, Johannes Pilic, Olaf Groß","doi":"10.1016/j.immuni.2024.10.012","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.10.012","url":null,"abstract":"How mitochondria reconcile roles in functionally divergent cell death pathways of apoptosis and NLRP3 inflammasome-mediated pyroptosis remains elusive, as is their precise role in NLRP3 activation and the evolutionarily conserved physiological function of NLRP3. Here, we have shown that when cells were challenged simultaneously, apoptosis was inhibited and NLRP3 activation prevailed. Apoptosis inhibition by structurally diverse NLRP3 activators, including nigericin, imiquimod, extracellular ATP, particles, and viruses, was not a consequence of inflammasome activation but rather of their effects on mitochondria. NLRP3 activators turned out as oxidative phosphorylation (OXPHOS) inhibitors, which we found to disrupt mitochondrial cristae architecture, leading to trapping of cytochrome c. Although this effect was alone not sufficient for NLRP3 activation, OXPHOS inhibitors became triggers of NLRP3 when combined with resiquimod or Yoda-1, suggesting that NLRP3 activation requires two simultaneous cellular signals, one of mitochondrial origin. Therefore, OXPHOS and apoptosis inhibition by NLRP3 activators provide stringency in cell death decisions.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"178 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673214","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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Targeting the aminopeptidase ERAP enhances antitumor immunity by disrupting the NKG2A-HLA-E inhibitory checkpoint 以氨基肽酶 ERAP 为靶点，通过破坏 NKG2A-HLA-E 抑制检查点增强抗肿瘤免疫力

IF 32.4 1区医学

Immunity Pub Date : 2024-11-18 DOI: 10.1016/j.immuni.2024.10.013

Hsiao-Wei Tsao, Seth Anderson, Kenneth J. Finn, Jonathan J. Perera, Lomax F. Pass, Emily M. Schneider, Aiping Jiang, Rachel Fetterman, Cun Lan Chuong, Kaiya Kozuma, Marcia M. Stickler, Marc Creixell, Susan Klaeger, Kshiti Meera Phulphagar, Suzanna Rachimi, Eva K. Verzani, Niclas Olsson, Juan Dubrot, Matthew F. Pech, Whitney Silkworth, Robert T. Manguso

{"title":"Targeting the aminopeptidase ERAP enhances antitumor immunity by disrupting the NKG2A-HLA-E inhibitory checkpoint","authors":"Hsiao-Wei Tsao, Seth Anderson, Kenneth J. Finn, Jonathan J. Perera, Lomax F. Pass, Emily M. Schneider, Aiping Jiang, Rachel Fetterman, Cun Lan Chuong, Kaiya Kozuma, Marcia M. Stickler, Marc Creixell, Susan Klaeger, Kshiti Meera Phulphagar, Suzanna Rachimi, Eva K. Verzani, Niclas Olsson, Juan Dubrot, Matthew F. Pech, Whitney Silkworth, Robert T. Manguso","doi":"10.1016/j.immuni.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.10.013","url":null,"abstract":"The aminopeptidase, endoplasmic reticulum aminopeptidase 1 (ERAP1), trims peptides for loading into major histocompatibility complex class I (MHC class I), and loss of this activity has broad effects on the MHC class I peptidome. Here, we investigated the impact of targeting ERAP1 in immune checkpoint blockade (ICB), as MHC class I interactions mediate both activating and inhibitory functions in antitumor immunity. Loss of ERAP sensitized mouse tumor models to ICB, and this sensitivity depended on CD8+ T cells and natural killer (NK) cells. In vivo suppression screens revealed that Erap1 deletion inactivated the inhibitory NKG2A-HLA-E checkpoint, which requires presentation of a restricted set of invariant epitopes (VL9) on HLA-E. Loss of ERAP altered the HLA-E peptidome, preventing NKG2A engagement. In humans, ERAP1 and ERAP2 showed functional redundancy for the processing and presentation of VL9, and loss of both inactivated the NKG2A checkpoint in cancer cells. Thus, loss of ERAP phenocopies the inhibition of the NKG2A-HLA-E pathway and represents an attractive approach to inhibit this critical checkpoint.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"99 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665526","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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CAR T cells in autoimmune disease: On the road to remission 自身免疫性疾病中的 CAR T 细胞：通往缓解之路

IF 32.4 1区医学

Immunity Pub Date : 2024-11-15 DOI: 10.1016/j.immuni.2024.10.011

Georg Schett, Carl H. June

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Sialylated IgG induces the transcription factor REST in alveolar macrophages to protect against lung inflammation and severe influenza disease Sialylated IgG 可诱导肺泡巨噬细胞中的转录因子 REST，从而防止肺部炎症和严重流感疾病的发生

IF 32.4 1区医学

Immunity Pub Date : 2024-11-13 DOI: 10.1016/j.immuni.2024.10.002

Saborni Chakraborty, Bowie Yik-Ling Cheng, Desmond L. Edwards, Joseph C. Gonzalez, David Kung-Chun Chiu, Hong Zheng, Courtney Scallan, Xinrong Guo, Gene S. Tan, Greg P. Coffey, Pamela B. Conley, Patrick S. Hume, William J. Janssen, Derek E. Byers, Philip A. Mudd, Jeffery Taubenberger, Matthew Memoli, Mark M. Davis, Katrin F. Chua, Michael S. Diamond, Taia T. Wang

{"title":"Sialylated IgG induces the transcription factor REST in alveolar macrophages to protect against lung inflammation and severe influenza disease","authors":"Saborni Chakraborty, Bowie Yik-Ling Cheng, Desmond L. Edwards, Joseph C. Gonzalez, David Kung-Chun Chiu, Hong Zheng, Courtney Scallan, Xinrong Guo, Gene S. Tan, Greg P. Coffey, Pamela B. Conley, Patrick S. Hume, William J. Janssen, Derek E. Byers, Philip A. Mudd, Jeffery Taubenberger, Matthew Memoli, Mark M. Davis, Katrin F. Chua, Michael S. Diamond, Taia T. Wang","doi":"10.1016/j.immuni.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.10.002","url":null,"abstract":"While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model. Mechanistic studies show that sialylated IgG mediated this protection by inducing the transcription factor repressor element-1 silencing transcription factor (REST), which repressed nuclear factor κB (NF-κB)-driven responses, preventing severe lung inflammation and protecting lung function during influenza infection. Therapeutic administration of a recombinant, sialylated Fc molecule in clinical development similarly activated REST and protected against severe influenza disease, demonstrating that this pathway could be clinically harnessed. Overall, induction of REST through sialylated IgG signaling is a strategy to limit inflammatory disease sequelae in infections caused by antigenically distinct influenza strains.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"3 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601061","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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Mx1-ing it up—Mitochondrial relay for interferon-dependent, unconventional IL-1β release in SLE monocytes Mx1-ing it up--系统性红斑狼疮单核细胞中干扰素依赖性、非常规 IL-1β 释放的线粒体继电器

IF 32.4 1区医学

Immunity Pub Date : 2024-11-12 DOI: 10.1016/j.immuni.2024.10.005

Andrea Dorfleutner, Christian Stehlik, Caroline A. Jefferies

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Home at last: Mixed signals guide memory T cells to residency 终于回家了混合信号引导记忆 T 细胞前往居住地

IF 32.4 1区医学

Immunity Pub Date : 2024-11-12 DOI: 10.1016/j.immuni.2024.10.008

Kalle Liimatta, Elina I. Zúñiga

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TKI resistance in brain metastasis: A CTLA4 state of mind 脑转移中的 TKI 抗药性：CTLA4 状态

IF 32.4 1区医学

Immunity Pub Date : 2024-11-12 DOI: 10.1016/j.immuni.2024.10.009

Elena Donders, Diether Lambrechts

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T cells standing at the gates of brain metastasis 站在脑转移大门口的 T 细胞

IF 32.4 1区医学

Immunity Pub Date : 2024-11-12 DOI: 10.1016/j.immuni.2024.10.006

Jan Remsik, Adrienne Boire

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Navigating the mutation maze: An oncogenic driver’s guide to macrophage reprogramming 穿越突变迷宫：巨噬细胞重编程的致癌驱动指南

IF 32.4 1区医学

Immunity Pub Date : 2024-11-12 DOI: 10.1016/j.immuni.2024.10.007

Ziyi Li, Ankur Sharma

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Maintenance and functional regulation of immune memory to COVID-19 vaccines in tissues 组织中 COVID-19 疫苗免疫记忆的维持和功能调节

IF 32.4 1区医学

Immunity Pub Date : 2024-11-06 DOI: 10.1016/j.immuni.2024.10.003

Julia Davis-Porada, Alex B. George, Nora Lam, Daniel P. Caron, Joshua I. Gray, Jenny Huang, Jennifer Hwu, Steven B. Wells, Rei Matsumoto, Masaru Kubota, YoonSeung Lee, Rory Morrison-Colvin, Isaac J. Jensen, Basak B. Ural, Namir Shaabani, Daniela Weiskopf, Alba Grifoni, Alessandro Sette, Peter A. Szabo, John R. Teijaro, Donna L. Farber

{"title":"Maintenance and functional regulation of immune memory to COVID-19 vaccines in tissues","authors":"Julia Davis-Porada, Alex B. George, Nora Lam, Daniel P. Caron, Joshua I. Gray, Jenny Huang, Jennifer Hwu, Steven B. Wells, Rei Matsumoto, Masaru Kubota, YoonSeung Lee, Rory Morrison-Colvin, Isaac J. Jensen, Basak B. Ural, Namir Shaabani, Daniela Weiskopf, Alba Grifoni, Alessandro Sette, Peter A. Szabo, John R. Teijaro, Donna L. Farber","doi":"10.1016/j.immuni.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.10.003","url":null,"abstract":"Memory T and B cells in tissues are essential for protective immunity. Here, we performed a comprehensive analysis of the tissue distribution, phenotype, durability, and transcriptional profile of COVID-19 mRNA vaccine-induced immune memory across blood, lymphoid organs, and lungs obtained from 63 vaccinated organ donors aged 23–86, some of whom experienced SARS-CoV-2 infection. Spike (S)-reactive memory T cells were detected in lymphoid organs and lungs and variably expressed tissue-resident markers based on infection history, and S-reactive B cells comprised class-switched memory cells resident in lymphoid organs. Compared with blood, S-reactive tissue memory T cells persisted for longer times post-vaccination and were more prevalent with age. S-reactive T cells displayed site-specific subset compositions and functions: regulatory cell profiles were enriched in tissues, while effector and cytolytic profiles were more abundant in circulation. Our findings reveal functional compartmentalization of vaccine-induced T cell memory where surveilling effectors and in situ regulatory responses confer protection with minimal tissue damage.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"90 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142588819","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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