Immunity最新文献_第4页

Targeting 7-Dehydrocholesterol Reductase Integrates Cholesterol Metabolism and IRF3 Activation to Eliminate Infection 靶向7-脱氢胆固醇还原酶整合胆固醇代谢和IRF3激活消除感染

IF 32.4 1区医学

Immunity Pub Date : 2025-04-25 DOI: 10.1016/j.immuni.2025.04.024

Jun Xiao, Weiyun Li, Xin Zheng, Linlin Qi, Hui Wang, Chi Zhang, Xiaopeng Wan, Yuxiao Zheng, Ruiyue Zhong, Xin Zhou, Yao Lu, Zhiqi Li, Ying Qiu, Chang Liu, Fang Zhang, Yanbo Zhang, Xiaoyan Xu, Zhongzhou Yang, Hualan Chen, Qiwei Zhai, Hongyan Wang

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B cell-derived acetylcholine promotes liver regeneration by regulating Kupffer cell and hepatic CD8+ T cell function B细胞源性乙酰胆碱通过调节Kupffer细胞和肝脏CD8+ T细胞功能促进肝脏再生

IF 32.4 1区医学

Immunity Pub Date : 2025-04-25 DOI: 10.1016/j.immuni.2025.04.002

Nastaran Fazel Modares, Liam D. Hendrikse, Logan K. Smith, Michael St. Paul, Jillian Haight, Ping Luo, Shaofeng Liu, Jerome Fortin, Frances K. Tong, Andrew C. Wakeham, Soode Moghadas Jafari, Chunxing Zheng, Mackenzie Buckland, Robert Flick, Jennifer Silvester, Thorsten Berger, Troy Ketela, Simone Helke, Erica Foffi, Raheleh Niavarani, Tak W. Mak

{"title":"B cell-derived acetylcholine promotes liver regeneration by regulating Kupffer cell and hepatic CD8+ T cell function","authors":"Nastaran Fazel Modares, Liam D. Hendrikse, Logan K. Smith, Michael St. Paul, Jillian Haight, Ping Luo, Shaofeng Liu, Jerome Fortin, Frances K. Tong, Andrew C. Wakeham, Soode Moghadas Jafari, Chunxing Zheng, Mackenzie Buckland, Robert Flick, Jennifer Silvester, Thorsten Berger, Troy Ketela, Simone Helke, Erica Foffi, Raheleh Niavarani, Tak W. Mak","doi":"10.1016/j.immuni.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.04.002","url":null,"abstract":"Liver regeneration (LR) is essential for recovery from acute trauma, cancer surgery, or transplantation. Neurotransmitters such as acetylcholine (ACh) play a role in LR by stimulating immune cells and augmenting hepatocyte proliferation, but the source of this ACh remains unclear. Here, we demonstrated that B cells expressing choline acetyltransferase (ChAT), which synthesizes ACh, were required for LR. Mice lacking ChAT+ B cells subjected to partial hepatectomy (PHX) displayed greater mortality due to failed LR. Kupffer cells and hepatic CD8+ T cells expressed the α7 nicotinic ACh receptor (nAChR), and LR was disrupted in mice lacking α7 nAChR. Mechanistically, B cell-derived ACh signaled through α7 nAChR to positively regulate the function of regenerative Kupffer cells and to control the activation of hepatic CD8+ T cells to curtail harmful interferon-gamma (IFNγ) production. Our work offers insights into LR mechanisms that may point to therapies for liver damage.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"25 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872396","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

Immunothrombolytic monocyte-neutrophil axes dominate the single-cell landscape of human thrombosis and correlate with thrombus resolution 免疫溶栓性单核细胞-中性粒细胞轴主导着人类血栓形成的单细胞景观，并与血栓溶解相关

IF 32.4 1区医学

Immunity Pub Date : 2025-04-24 DOI: 10.1016/j.immuni.2025.03.020

Kami Pekayvaz, Badr Kilani, Markus Joppich, Luke Eivers, Sophia Brambs, Viktoria Knottenberg, Sezer Akgöl, Keyang Yue, Lukas Li, Alejandro Martinez-Navarro, Rainer Kaiser, Nina Meißner, Heiko Schulz, Larissa Belz, Anastassia Akhalkatsi, Sven Stockhausen, Tonina T. Mueller, Simon Millonig, Lea Hartelt, Christoph Gold, Konstantin Stark

{"title":"Immunothrombolytic monocyte-neutrophil axes dominate the single-cell landscape of human thrombosis and correlate with thrombus resolution","authors":"Kami Pekayvaz, Badr Kilani, Markus Joppich, Luke Eivers, Sophia Brambs, Viktoria Knottenberg, Sezer Akgöl, Keyang Yue, Lukas Li, Alejandro Martinez-Navarro, Rainer Kaiser, Nina Meißner, Heiko Schulz, Larissa Belz, Anastassia Akhalkatsi, Sven Stockhausen, Tonina T. Mueller, Simon Millonig, Lea Hartelt, Christoph Gold, Konstantin Stark","doi":"10.1016/j.immuni.2025.03.020","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.03.020","url":null,"abstract":"Thrombotic diseases remain the major cause of death and disability worldwide, and the contribution of inflammation is increasingly recognized. Thromboinflammation has been identified as a key pathomechanism, but an unsupervised map of immune-cell states, trajectories, and intercommunication at a single-cell level has been lacking.Here, we reveal innate leukocyte substates with prominent thrombolytic properties by employing single-cell omics measures on human stroke thrombi. Using in vivo and in vitro thrombosis models, we propose a pro-resolving monocyte-neutrophil axis, combining two properties: (1) NR4A1hi non-classical monocytes acquire a thrombolytic and neutrophil-chemoattractive phenotype, and (2) blood neutrophils are thereby continuously recruited to established thrombi through CXCL8-CXCR1 and CXCR2 and adopt a hypoxia-induced thrombus-resolving urokinase receptor (PLAUR)+ phenotype. This immunothrombolytic axis results in thrombus resolution. Together, with this immune landscape of thrombosis, we provide a valuable resource and introduce the concept of “immunothrombolysis” with broad mechanistic and translational implications at the crossroad of inflammation and thrombosis.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"32 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867197","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

Regulatory T cell depletion promotes myeloid cell activation and glioblastoma response to anti-PD1 and tumor-targeting antibodies 调节性T细胞耗竭促进髓细胞活化和胶质母细胞瘤对抗pd1和肿瘤靶向抗体的反应

IF 32.4 1区医学

Immunity Pub Date : 2025-04-24 DOI: 10.1016/j.immuni.2025.03.021

Felipe Galvez-Cancino, Mariela Navarrete, Gordon Beattie, Simone Puccio, Enrique Conde-Gallastegi, Kane Foster, Yasmin Morris, Teerapon Sahwangarrom, Despoina Karagianni, Jiali Liu, Alvin J.X. lee, Dimitrios A. Garyfallos, Alexander P. Simpson, Gerasimos-Theodoros Mastrokalos, Francesco Nannini, Cristobal Costoya, Varshaa Anantharam, Beatrice Claudia Cianciotti, Leanne Bradley, Claudia Garcia-Diaz, Sergio A. Quezada

{"title":"Regulatory T cell depletion promotes myeloid cell activation and glioblastoma response to anti-PD1 and tumor-targeting antibodies","authors":"Felipe Galvez-Cancino, Mariela Navarrete, Gordon Beattie, Simone Puccio, Enrique Conde-Gallastegi, Kane Foster, Yasmin Morris, Teerapon Sahwangarrom, Despoina Karagianni, Jiali Liu, Alvin J.X. lee, Dimitrios A. Garyfallos, Alexander P. Simpson, Gerasimos-Theodoros Mastrokalos, Francesco Nannini, Cristobal Costoya, Varshaa Anantharam, Beatrice Claudia Cianciotti, Leanne Bradley, Claudia Garcia-Diaz, Sergio A. Quezada","doi":"10.1016/j.immuni.2025.03.021","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.03.021","url":null,"abstract":"Glioblastoma is invariably lethal and responds poorly to immune checkpoint blockade. Here, we examined the impact of regulatory T (Treg) cell depletion on glioblastoma progression and immunotherapy responsiveness. In human glioblastoma, elevated Treg cell signatures correlated with poorer survival outcomes, with these cells expressing high levels of CD25. In Nf1−/−Pten−/−EGFRvIII+ glioblastoma-bearing mice, a single dose of non-interleukin-2 (IL-2) blocking (NIB) anti-CD25 (anti-CD25NIB) antibody depleted Treg cells and promoted CD8+ T cell clonal expansion and partial tumor control, further enhanced by programmed cell death-1 (PD1)-blockade. Treg cell depletion induced interferon-γ (IFN-γ)-dependent tumor microenvironment remodeling, increasing Fcγ receptor (FcγR) expression on intratumoral myeloid cells and enhancing phagocytosis. Combination of anti-CD25NIB with anti-EGFRvIII tumor-targeting antibodies resulted in complete tumor control. Anti-human CD25NIB treatment of glioblastoma patient-derived tumor fragments effectively depleted Treg cells and activated CD8+ T cells. These findings underscore the therapeutic relevance of Treg targeting in glioblastoma and unveil potent combination strategies for anti-CD25NIB based on innate cell activation.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"259 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867209","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

Acute exposure to high-fat diet impairs ILC3 functions and gut homeostasis 急性暴露于高脂肪饮食会损害 ILC3 功能和肠道稳态

IF 32.4 1区医学

Immunity Pub Date : 2025-04-14 DOI: 10.1016/j.immuni.2025.03.017

Le Xiong, Shanti Diwakarla, Roxanne Chatzis, Olivia Artaiz, Matthew Macowan, Shengbo Zhang, Alexandra Garnham, Pooranee K. Morgan, Natalie A. Mellett, Peter J. Meikle, Graeme I. Lancaster, Benjamin J. Marsland, Stephen L. Nutt, Cyril Seillet

{"title":"Acute exposure to high-fat diet impairs ILC3 functions and gut homeostasis","authors":"Le Xiong, Shanti Diwakarla, Roxanne Chatzis, Olivia Artaiz, Matthew Macowan, Shengbo Zhang, Alexandra Garnham, Pooranee K. Morgan, Natalie A. Mellett, Peter J. Meikle, Graeme I. Lancaster, Benjamin J. Marsland, Stephen L. Nutt, Cyril Seillet","doi":"10.1016/j.immuni.2025.03.017","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.03.017","url":null,"abstract":"Prolonged exposure to a high-fat diet (HFD) exacerbates intestinal disease pathology, yet the early events preceding the development of gut inflammation remain poorly understood. Here, we show that within 48 h, HFD impairs intestinal group 3 innate lymphoid cells (ILC3s) and their capacity to produce interleukin-22 (IL-22), critical for maintaining gut homeostasis. This loss of function was associated with rapid dysbiosis, increased gut permeability, and reduced production of antimicrobial peptides, mucus, and tight-junction proteins. While saturated fatty acids metabolized through oxidation impaired ILC3 function, unsaturated fatty acids sustained IL-22 secretion by ILC3s through the formation of lipid droplets using diacylglycerol O-acyltransferase (DGAT) enzymes. Upon inflammation, saturated fatty acids impaired IL-22 production by ILC3s and increased the susceptibility of the gut to injury. Our findings reveal the differential acute impact of saturated and unsaturated fatty acids on gut homeostasis through distinct metabolic pathways in ILC3s.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"90 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827146","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

A. faecalis induces intestinal T helper 17 cells by promoting E3 ubiquitin ligase Trim21-mediated E3 ubiquitin ligase Fbxw7 degradation 粪芽孢杆菌通过促进E3泛素连接酶trim21介导的E3泛素连接酶Fbxw7降解诱导肠道T辅助性17细胞

IF 32.4 1区医学

Immunity Pub Date : 2025-04-10 DOI: 10.1016/j.immuni.2025.03.008

Yingying Shen, Zeyu Ma, Hanliang Wang, Yinghu Chen, Yue Fang, Lionel Apetoh, Gensheng Zhang, Fenglian He, Shaofang Xie, Jufeng Guo, Shuaikang Cao, Hai Li, Qingqing Wang, Jianli Wang, Junjie Xu, Zhijian Cai

{"title":"A. faecalis induces intestinal T helper 17 cells by promoting E3 ubiquitin ligase Trim21-mediated E3 ubiquitin ligase Fbxw7 degradation","authors":"Yingying Shen, Zeyu Ma, Hanliang Wang, Yinghu Chen, Yue Fang, Lionel Apetoh, Gensheng Zhang, Fenglian He, Shaofang Xie, Jufeng Guo, Shuaikang Cao, Hai Li, Qingqing Wang, Jianli Wang, Junjie Xu, Zhijian Cai","doi":"10.1016/j.immuni.2025.03.008","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.03.008","url":null,"abstract":"Segmented filamentous bacteria are essential for intestinal T helper 17 (Th17) cell induction, but their colonization in the adult intestine is controversial. Therefore, whether there are gut microbiota (GMs) that mediate Th17 cell generation in humans of different ages is elusive. Here, we reported that colonization of ubiquitous Alcaligenes faecalis was sufficient to induce intestinal Th17 cells. Alcaligenes faecalis proteins were endocytosed by CD4+ T cells in a manner dependent on the small GTPase CDC42, inhibiting the interaction between E2 ubiquitin-conjugating enzyme Ube2w and E3 ubiquitin ligase Trim21, thereby reducing Trim21 self-ubiquitination and degradation, which increased Trim21-induced E3 ubiquitin ligase Fbxw7 degradation and JunB accumulation, subsequently promoting Ahr and Rorc transcription, thus enhancing intestinal Th17 cell differentiation. Furthermore, outer membrane vesicles from Alcaligenes faecalis also induced intestinal Th17 cells in a Trim21-Fbxw7-axis-dependent manner. Altogether, these results reveal a vital role for the Trim21-Fbxw7 axis in intestinal Th17 cell enrichments among most humans.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"25 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814259","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

Michael Cancro (1949–2025) 迈克尔·坎柯（1949-2025）

IF 32.4 1区医学

Immunity Pub Date : 2025-04-08 DOI: 10.1016/j.immuni.2025.03.011

Mark J. Shlomchik, David Allman

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T cells with a taste for tissue remodeling 有组织重塑嗜好的T细胞

IF 32.4 1区医学

Immunity Pub Date : 2025-04-08 DOI: 10.1016/j.immuni.2025.03.012

Greet Verstichel, Hilde Cheroutre

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More than the sum: How vascular endothelial growth factor inhibition unlocks the full potential of immune checkpoint blockade 超过总和：血管内皮生长因子抑制如何解锁免疫检查点封锁的全部潜力