Immunity最新文献_第6页

Single-cell transcriptomic and functional studies identify glial state changes and a role for inflammatory RIPK1 signaling in ALS pathogenesis 单细胞转录组学和功能研究确定了胶质状态的变化和炎症RIPK1信号在ALS发病机制中的作用

IF 32.4 1区医学

Immunity Pub Date : 2025-03-24 DOI: 10.1016/j.immuni.2025.02.024

Matija Zelic, Anna Blazier, Fabrizio Pontarelli, Michael LaMorte, Jeremy Huang, Ozge E. Tasdemir-Yilmaz, Yi Ren, Sean K. Ryan, Cynthia Shapiro, Caroline Morel, Pavithra Krishnaswami, Mikhail Levit, Disha Sood, Yao Chen, Joseph Gans, Xinyan Tang, Jennifer Hsiao-Nakamoto, Fen Huang, Bailin Zhang, James D. Berry, Timothy R. Hammond

{"title":"Single-cell transcriptomic and functional studies identify glial state changes and a role for inflammatory RIPK1 signaling in ALS pathogenesis","authors":"Matija Zelic, Anna Blazier, Fabrizio Pontarelli, Michael LaMorte, Jeremy Huang, Ozge E. Tasdemir-Yilmaz, Yi Ren, Sean K. Ryan, Cynthia Shapiro, Caroline Morel, Pavithra Krishnaswami, Mikhail Levit, Disha Sood, Yao Chen, Joseph Gans, Xinyan Tang, Jennifer Hsiao-Nakamoto, Fen Huang, Bailin Zhang, James D. Berry, Timothy R. Hammond","doi":"10.1016/j.immuni.2025.02.024","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.024","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss. Microglia and astrocyte-driven neuroinflammation is prominent in ALS, but the cell state dynamics and pathways driving disease remain unclear. We performed single-nucleus RNA sequencing of ALS spinal cords and identified altered glial cell states, including increased expression of inflammatory and glial activation markers. Many of these signals converged on the inflammation and cell death regulator receptor-interacting protein kinase 1 (RIPK1) and the necroptotic cell death pathway. In superoxide dismutase 1 (SOD1)G93A mice, blocking RIPK1 kinase activity delayed symptom onset and motor impairment and modulated glial responses. We used human induced pluripotent stem cell (iPSC)-derived motor neuron, astrocyte, and microglia tri-cultures to identify potential biomarkers that are secreted upon RIPK1 activation in vitro and modulated by RIPK1 inhibition in the cerebrospinal fluid (CSF) of people with ALS. These data reveal ALS-enriched glial populations associated with inflammation and suggest a deleterious role for neuroinflammatory signaling in ALS pathogenesis.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"25 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677861","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

Long-lasting B cell convergence to distinct broadly reactive epitopes following vaccination with chimeric influenza virus hemagglutinins 接种嵌合流感病毒血凝素后，B细胞长时间趋同到不同的广泛反应性表位

IF 32.4 1区医学

Immunity Pub Date : 2025-03-24 DOI: 10.1016/j.immuni.2025.02.025

Jenna J. Guthmiller, Linda Yu-Ling Lan, Lei Li, Yanbin Fu, Sean A. Nelson, Carole Henry, Christopher T. Stamper, Henry A. Utset, Alec W. Freyn, Julianna Han, Olivia Stovicek, Jiaolong Wang, Nai-Ying Zheng, Min Huang, Haley L. Dugan, Micah E. Tepora, Xueyong Zhu, Yao-Qing Chen, Anna-Karin E. Palm, Dustin G. Shaw, Patrick C. Wilson

{"title":"Long-lasting B cell convergence to distinct broadly reactive epitopes following vaccination with chimeric influenza virus hemagglutinins","authors":"Jenna J. Guthmiller, Linda Yu-Ling Lan, Lei Li, Yanbin Fu, Sean A. Nelson, Carole Henry, Christopher T. Stamper, Henry A. Utset, Alec W. Freyn, Julianna Han, Olivia Stovicek, Jiaolong Wang, Nai-Ying Zheng, Min Huang, Haley L. Dugan, Micah E. Tepora, Xueyong Zhu, Yao-Qing Chen, Anna-Karin E. Palm, Dustin G. Shaw, Patrick C. Wilson","doi":"10.1016/j.immuni.2025.02.025","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.025","url":null,"abstract":"In a phase 1 clinical trial, a chimeric hemagglutinin (cHA) immunogen induced antibody responses against the conserved hemagglutinin (HA) stalk domain as designed. Here, we determined the specificity, function, and subsets of B cells induced by cHA vaccination by pairing single-cell RNA sequencing and B cell receptor repertoire sequencing. We have shown that the cHA-inactivated vaccine with a squalene-based adjuvant induced a robust activated B cell and memory B cell (MBC) phenotype against two broadly neutralizing epitopes in the stalk domain. The overall specificities of the acute plasmablast (PB) and MBC responses clonally overlapped, suggesting B cell convergence to these broadly protective epitopes. At 1 year post immunization, we identified that cHA vaccination reshaped the HA-specific MBC pool to enrich for stalk-binding B cells. Altogether, these data indicate the cHA vaccine induced robust and durable B cell responses against broadly protective epitopes of the HA stalk domain, in line with serological data.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"49 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677860","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

Particle uptake by macrophages triggers bifurcated transcriptional pathways that differentially regulate inflammation and lysosomal gene expression 巨噬细胞的颗粒摄取触发了不同的转录途径，不同地调节炎症和溶酶体基因表达

IF 32.4 1区医学

Immunity Pub Date : 2025-03-20 DOI: 10.1016/j.immuni.2025.02.023

Isidoro Cobo, Jessica Murillo, Mohnish Alishala, Stephen Calderon, Roxana Coras, Benjamin Hemming, Faith Inkum, Fiorella Rosas, Riku Takei, Nathan Spann, Thomas A. Prohaska, Paulo V.G. Alabarse, Se-Jin Jeong, Christian K. Nickl, Anyan Cheng, Benjamin Li, Andrea Vogel, Thomas Weichhart, José J. Fuster, Thomas Le, Christopher K. Glass

{"title":"Particle uptake by macrophages triggers bifurcated transcriptional pathways that differentially regulate inflammation and lysosomal gene expression","authors":"Isidoro Cobo, Jessica Murillo, Mohnish Alishala, Stephen Calderon, Roxana Coras, Benjamin Hemming, Faith Inkum, Fiorella Rosas, Riku Takei, Nathan Spann, Thomas A. Prohaska, Paulo V.G. Alabarse, Se-Jin Jeong, Christian K. Nickl, Anyan Cheng, Benjamin Li, Andrea Vogel, Thomas Weichhart, José J. Fuster, Thomas Le, Christopher K. Glass","doi":"10.1016/j.immuni.2025.02.023","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.023","url":null,"abstract":"Exposure to particles is a driver of several inflammatory diseases. Here, we investigated macrophage responses to monosodium urate crystals, calcium pyrophosphate crystals, aluminum salts, and silica nanoparticles. While each particle induced a distinct gene expression pattern, we identified a common inflammatory signature and acute activation of lysosomal acidification genes. Using monosodium urate crystals as a model, we demonstrated that this lysosomal gene program is regulated by a 5′-prime-AMP-activated protein kinase (AMPK)-dependent transcriptional network, including TFEB, TFE3, and the epigenetic regulators DNA methyl transferase 3a (DNMT3A) and DOT1L. This lysosomal acidification program operates in parallel with, but largely independently of, a JNK-AP-1-dependent network driving crystal-induced chemokine and cytokine expression. These findings reveal a bifurcation in pathways governing inflammatory and lysosomal responses, offering insights for treating particle-associated diseases.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"183 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660419","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

An interleukin-9-ZBTB18 axis promotes germinal center development of memory B cells 白细胞介素-9- zbtb18轴促进记忆B细胞生发中心的发育

IF 32.4 1区医学

Immunity Pub Date : 2025-03-18 DOI: 10.1016/j.immuni.2025.02.021

Xiaocui Luo, Xiaoxiao Hou, Yifeng Wang, Ye Li, Shangcheng Yu, Hai Qi

{"title":"An interleukin-9-ZBTB18 axis promotes germinal center development of memory B cells","authors":"Xiaocui Luo, Xiaoxiao Hou, Yifeng Wang, Ye Li, Shangcheng Yu, Hai Qi","doi":"10.1016/j.immuni.2025.02.021","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.021","url":null,"abstract":"Memory B cell (MBC) development from germinal centers (GCs) entails profound changes in cell cycling, localization, and survival. Here, we examined the mechanisms that induce the memory program, focusing on interleukin (IL)-9, given its importance for normal recall antibody responses. Using adoptive transfer and radiation chimera models, we found that T cell-derived IL-9 was required for MBC development and function. By contrast, B cells deficient in IL-9 generated functionally normal MBCs that support antibody recall normally. IL-9 induced expression of the transcriptional repressor ZBTB18 in GC memory precursor cells and MBCs. ZBTB18 was dispensable for naive B cell activation and GC formation but required for the development of GC-derived MBCs. ZBTB18 directly repressed the expression of a suite of genes encoding cyclin and cyclin-dependent kinases, pro-apoptotic genes Bid and Casp3, and the GC-retaining factor S1pr2. Lack of IL-9-mediated instruction or intrinsic programming by ZBTB18 impaired GC-derived MBC development and antibody recall. Thus, an IL-9-ZBTB18 axis instructs the development of functional B cell memory from GCs.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"14 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640501","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

Single-cell atlas of endothelial and mural cells across primary and metastatic brain tumors 原发性和转移性脑肿瘤内皮细胞和壁细胞的单细胞图谱

IF 32.4 1区医学

Immunity Pub Date : 2025-03-18 DOI: 10.1016/j.immuni.2025.02.022

Leire Bejarano, Joao Lourenco, Annamaria Kauzlaric, Eleni Lamprou, Catia F. Costa, Sabine Galland, Roeltje R. Maas, Paola Guerrero Aruffo, Nadine Fournier, Jean-Philippe Brouland, Andreas F. Hottinger, Roy T. Daniel, Monika E. Hegi, Johanna A. Joyce

{"title":"Single-cell atlas of endothelial and mural cells across primary and metastatic brain tumors","authors":"Leire Bejarano, Joao Lourenco, Annamaria Kauzlaric, Eleni Lamprou, Catia F. Costa, Sabine Galland, Roeltje R. Maas, Paola Guerrero Aruffo, Nadine Fournier, Jean-Philippe Brouland, Andreas F. Hottinger, Roy T. Daniel, Monika E. Hegi, Johanna A. Joyce","doi":"10.1016/j.immuni.2025.02.022","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.022","url":null,"abstract":"Central nervous system (CNS) malignancies include primary tumors, such as gliomas, and brain metastases (BrMs) originating from diverse extracranial cancers. The blood-brain barrier (BBB) is a key structural component of both primary and metastatic brain cancers. Here, we comprehensively analyzed the two major BBB cell types, endothelial and mural cells, across non-tumor brain tissue, isocitrate dehydrogenase (IDH) mutant (IDH mut) low-grade gliomas, IDH wild-type (IDH WT) high-grade glioblastomas (GBMs), and BrMs from various primary tumors. Bulk and single-cell RNA sequencing, integrated with spatial analyses, revealed that GBMs, but not low-grade gliomas, exhibit significant alterations in the tumor vasculature, including the emergence of diverse pathological vascular cell subtypes. However, these alterations are less pronounced in GBMs than in BrMs. Notably, the BrM vasculature shows higher permeability and more extensive interactions with distinct immune cell populations. This vascular atlas presents a resource toward understanding of tumor-specific vascular features in the brain, providing a foundation for developing vascular- and immune-targeting therapies.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"61 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640500","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

Anti-vascular endothelial growth factor treatment potentiates immune checkpoint blockade through a BAFF- and IL-12-dependent reprogramming of the TME 抗血管内皮生长因子治疗通过BAFF和il -12依赖性TME重编程增强免疫检查点阻断

IF 32.4 1区医学

Immunity Pub Date : 2025-03-14 DOI: 10.1016/j.immuni.2025.02.017

Mohamed-Reda Benmebarek, Cihan Oguz, Matthias Seifert, Benjamin Ruf, Yuta Myojin, Kylynda C. Bauer, Patrick Huang, Chi Ma, Marina Villamor-Payà, Francisco Rodriguez-Matos, Marlaine Soliman, Rajiv Trehan, Cecilia Monge, Changqing Xie, David E. Kleiner, Bradford J. Wood, Elliot B. Levy, Anuradha Budhu, Noemi Kedei, Christian T. Mayer, Tim F. Greten

{"title":"Anti-vascular endothelial growth factor treatment potentiates immune checkpoint blockade through a BAFF- and IL-12-dependent reprogramming of the TME","authors":"Mohamed-Reda Benmebarek, Cihan Oguz, Matthias Seifert, Benjamin Ruf, Yuta Myojin, Kylynda C. Bauer, Patrick Huang, Chi Ma, Marina Villamor-Payà, Francisco Rodriguez-Matos, Marlaine Soliman, Rajiv Trehan, Cecilia Monge, Changqing Xie, David E. Kleiner, Bradford J. Wood, Elliot B. Levy, Anuradha Budhu, Noemi Kedei, Christian T. Mayer, Tim F. Greten","doi":"10.1016/j.immuni.2025.02.017","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.017","url":null,"abstract":"Anti-vascular endothelial growth factor (VEGF) treatment has shown clinical activity together with immune checkpoint blockade (ICB), but the exact mechanism is not known. We show that VEGF blockade in combination with anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) + anti-programmed death-ligand 1 (PD-L1) in cholangiocarcinoma (CCA) potentiated a multimodal mechanism dependent on B cell activating factor (BAFF), leading to a proinflammatory B cell response. It led to a BAFF- and interleukin (IL)-12-dependent expansion and rewiring of T regulatory cells (Tregs) toward an anti-tumor T helper-1 (Th-1)-like fragile state. We translated this approach to the clinic and observed immunological changes characterized by Treg cell expansion and rewiring toward fragile and unstable states. We explored the effect of VEGF receptor 2 (VEGFR2) signaling on Treg cell transcriptional programming and established a mouse model ablating VEGFR2 expression on Treg cells. This study reveals the immunological interplay resulting from targeting VEGF together with CTLA-4 and PD-L1 blockade.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"23 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618561","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

NK resident memory cells arise from NK cells that accumulate in tissues independently of persistent local infection NK常驻记忆细胞是由NK细胞在组织中积累而产生的，不受持续局部感染的影响

IF 32.4 1区医学

Immunity Pub Date : 2025-03-11 DOI: 10.1016/j.immuni.2025.02.019

Iona S. Schuster, Matthew E. Wikstrom, Christopher E. Andoniou, Mariapia A. Degli-Esposti

引用次数: 0

Lactate: A key regulator of the immune response 乳酸：免疫反应的关键调节因子

IF 32.4 1区医学

Immunity Pub Date : 2025-03-11 DOI: 10.1016/j.immuni.2025.02.008

Alba Llibre, Salih Kucuk, Atrayee Gope, Michelangelo Certo, Claudio Mauro

引用次数: 0

Parts and ICRAFTs: Finding new immunotherapy targets 零件和工艺品：寻找新的免疫治疗靶点