Immunity最新文献_第2页

Cognate interaction-dependent pathogenicity of meningeal B cells drives neuroinflammation relapse 脑膜B细胞同源相互作用依赖性致病性驱动神经炎症复发

IF 32.4 1区医学

Immunity Pub Date : 2025-07-15 DOI: 10.1016/j.immuni.2025.06.016

Yan Wang, Di Xu, Shaorui Liu, Haoyang Li, Yinsheng Wang, Hui Li, Heping Xu, Danyang He

{"title":"Cognate interaction-dependent pathogenicity of meningeal B cells drives neuroinflammation relapse","authors":"Yan Wang, Di Xu, Shaorui Liu, Haoyang Li, Yinsheng Wang, Hui Li, Heping Xu, Danyang He","doi":"10.1016/j.immuni.2025.06.016","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.06.016","url":null,"abstract":"B cells are central drivers of central nervous system (CNS) autoimmune disorders, including multiple sclerosis (MS). Although the brain meninges normally maintain a stringently non-self-reactive B cell repertoire, how disruption of this local immune tolerance contributes to pathology remains unclear. Here, we demonstrated that autoreactive B cells at the brain border accelerated neuroinflammation by directly engaging encephalitogenic T cells. Intracisterna magna injections, used to selectively manipulate meningeal B cell populations in the 2D2 transfer experimental autoimmune encephalomyelitis (EAE) model, revealed that autoreactive B-T interactions in the leptomeninges amplified a local pro-inflammatory loop, promoting neutrophil recruitment and endothelial activation before disease onset. This mechanism required major histocompatibility complex class II (MHC class II) expression by B cells and granulocyte-macrophage colony-stimulating factor (GM-CSF) production by T cells. Furthermore, targeted depletion of brain-localized B cells attenuated EAE relapses in a passive EAE model. These findings establish brain-localized autoreactive B cells as crucial initiators of neuroinflammation and promising therapeutic targets in relapsing MS.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"10 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629957","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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Systems analysis of clinical malaria reveals proteomic perturbation and innate-adaptive crosstalk linked to disease severity 临床疟疾的系统分析揭示了与疾病严重程度相关的蛋白质组紊乱和先天适应性串扰

IF 32.4 1区医学

Immunity Pub Date : 2025-07-14 DOI: 10.1016/j.immuni.2025.06.014

Maximilian Julius Lautenbach, Katja Wyss, Victor Yman, Fariba Foroogh, Donya Satarvandi, Zaynab Mousavian, Klara Sondén, Jun Wang, María Bueno Álvez, Sofia Bergström, Peter Nilsson, Fredrik Edfors, Petter Brodin, Mathias Uhlén, Christopher Sundling, Anna Färnert

{"title":"Systems analysis of clinical malaria reveals proteomic perturbation and innate-adaptive crosstalk linked to disease severity","authors":"Maximilian Julius Lautenbach, Katja Wyss, Victor Yman, Fariba Foroogh, Donya Satarvandi, Zaynab Mousavian, Klara Sondén, Jun Wang, María Bueno Álvez, Sofia Bergström, Peter Nilsson, Fredrik Edfors, Petter Brodin, Mathias Uhlén, Christopher Sundling, Anna Färnert","doi":"10.1016/j.immuni.2025.06.014","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.06.014","url":null,"abstract":"Malaria presents with varying degrees of severity. To improve clinical management and prevention, it is crucial to understand the pathogenesis and host response. We analyzed 1,463 plasma proteins during and after acute Plasmodium falciparum malaria in adult travelers and linked responses to peripheral immune cells by integrating with single-cell RNA sequencing (RNA-seq) data from a subset of donors. We identified extensive perturbations in over 250 proteins with diverse origins, including many not previously analyzed in malaria patients, such as hormones, circulating receptors, and intracellular or membrane-bound proteins from affected tissues. The protein profiles clustered participants according to disease severity, enabling the identification of a compressed 11-protein signature enriched in severe malaria. Conceptually, this study advances our understanding of malaria by linking systemic proteomic changes to immune cell communication and organ-specific responses. This resource, which includes an interactive platform to explore data, opens new avenues for hypothesis generation, biomarker discovery, and therapeutic target identification.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"4 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622369","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

Mitochondrial control of macrophage polarity in tumors 肿瘤中巨噬细胞极性的线粒体控制

IF 32.4 1区医学

Immunity Pub Date : 2025-07-08 DOI: 10.1016/j.immuni.2025.06.008

Máté Kiss, Mikael J. Pittet

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The Three Graces of T cell receptor Vγ9Vδ2 chain activation T细胞受体v - γ - 9v - δ2链活化的三种恩典

IF 32.4 1区医学

Immunity Pub Date : 2025-07-08 DOI: 10.1016/j.immuni.2025.06.009

José Pedro Loureiro, Gennaro De Libero

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RORγt+ dendritic cells and regulatory T cells: A couple hiding in the shadows rorγ - T +树突状细胞和调节性T细胞：隐藏在阴影中的一对

IF 32.4 1区医学

Immunity Pub Date : 2025-07-08 DOI: 10.1016/j.immuni.2025.06.012

Brian L. Kelsall

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Neuro-immune ChATing protects the heart 神经免疫欺骗保护心脏

IF 32.4 1区医学

Immunity Pub Date : 2025-07-08 DOI: 10.1016/j.immuni.2025.06.007

Teresa Gerhardt, Cameron S. McAlpine

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Who is who in differentiation of Trm-like TIL trm样TIL的鉴别是谁

IF 32.4 1区医学

Immunity Pub Date : 2025-07-08 DOI: 10.1016/j.immuni.2025.06.013

Artun Bülbül, Julian Hönninger, Veit R. Buchholz

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The costimulatory molecule ICOS limits memory-like properties and function of exhausted PD-1+CD8+ T cells 共刺激分子ICOS限制了耗竭的PD-1+CD8+ T细胞的记忆样特性和功能

IF 32.4 1区医学

Immunity Pub Date : 2025-07-07 DOI: 10.1016/j.immuni.2025.06.001

Etienne Humblin, Isabel Korpas, Nataliya Prokhnevska, Abishek Vaidya, Dan Filipescu, Jiahua Lu, Verena van der Heide, Carlos Alberto de Carvalho Fraga, Tesia Bobrowski, Adam Marks, Matthew D. Park, Helder I. Nakaya, Emily Bernstein, Brian D. Brown, Amaia Lujambio, David Dominguez-Sola, Brad R. Rosenberg, Alice O. Kamphorst

{"title":"The costimulatory molecule ICOS limits memory-like properties and function of exhausted PD-1+CD8+ T cells","authors":"Etienne Humblin, Isabel Korpas, Nataliya Prokhnevska, Abishek Vaidya, Dan Filipescu, Jiahua Lu, Verena van der Heide, Carlos Alberto de Carvalho Fraga, Tesia Bobrowski, Adam Marks, Matthew D. Park, Helder I. Nakaya, Emily Bernstein, Brian D. Brown, Amaia Lujambio, David Dominguez-Sola, Brad R. Rosenberg, Alice O. Kamphorst","doi":"10.1016/j.immuni.2025.06.001","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.06.001","url":null,"abstract":"During persistent antigen stimulation, CD8+ T cell responses are maintained by progenitor exhausted CD8+ T (Tpex) cells. Tpex cells respond to blockade of the inhibitory receptor programmed cell death-1 (PD-1), and regulation of their differentiation is critical for immunotherapies. Tpex cells highly express inducible costimulator (ICOS), but how ICOS modulates PD-1+CD8+ T cells is not clear. During chronic infection, intrinsic ICOS deficiency increased number and quality of virus-specific CD8+ T cells. Loss of ICOS potentiated activity of the transcription factor forkhead box O1 (FoxO1) and memory-like features of Tpex cells. ICOS-deficient Tpex cells were poised to generate effecor-like cells with improved survival and cytokine production. ICOS-ligand (ICOSL) blockade expanded effector-like PD-1+CD8+ T cells, reduced viral load, and improved response to PD-1 blockade. Similarly, in a mouse model of hepatocellular carcinoma, ICOS inhibition enhanced tumor-specific CD8+ T cell responses and tumor control by PD-1 blockade. Overall, we show that sustained ICOS costimulation limits CD8+ T cell responses during chronic antigen exposure.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"21 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568951","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

Excitatory-neuron-derived interleukin-34 supports cortical developmental microglia function 兴奋性神经元来源的白介素-34支持皮层发育小胶质细胞功能

IF 32.4 1区医学

Immunity Pub Date : 2025-07-02 DOI: 10.1016/j.immuni.2025.06.002

Benjamin A. Devlin, Dang M. Nguyen, Diogo Ribeiro, Gabriel Grullon, Madeline J. Clark, Amelie Finn, Alexis M. Ceasrine, Seneca Oxendine, Martha Deja, Ashka Shah, Shomik Ati, Anne Schaefer, Staci D. Bilbo

{"title":"Excitatory-neuron-derived interleukin-34 supports cortical developmental microglia function","authors":"Benjamin A. Devlin, Dang M. Nguyen, Diogo Ribeiro, Gabriel Grullon, Madeline J. Clark, Amelie Finn, Alexis M. Ceasrine, Seneca Oxendine, Martha Deja, Ashka Shah, Shomik Ati, Anne Schaefer, Staci D. Bilbo","doi":"10.1016/j.immuni.2025.06.002","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.06.002","url":null,"abstract":"Neuron-microglia interactions dictate the development of neuronal circuits in the brain. However, the factors that regulate these processes across development are largely unknown. Here, we found that interleukin-34 (IL-34), a neuron-derived cytokine, was upregulated in early development and maintained neuroprotective, mature microglia in the anterior cingulate cortex (ACC) of mice. IL-34 expression increases in the second week of post-natal life and was primarily produced by excitatory neurons. Excitatory-neuron-specific deletion of IL-34 reduced microglia numbers and microglial TMEM119 expression and increased aberrant microglial phagocytosis of excitatory thalamocortical synapses in the ACC. Acute, low-dose blocking of IL-34 at post-natal day 15 similarly decreased microglial TMEM119 and aberrantly increased microglial phagocytosis of synapses. Viral overexpression of IL-34 induced TMEM119 expression and prevented appropriate microglial phagocytosis of synapses. These findings establish IL-34 as a key regulator of neuron-microglia crosstalk in post-natal brain development, controlling both microglial maturation and synapse engulfment.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"647 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533905","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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More TOR: The expanding role of mTOR in regulating immune responses 更多的TOR: mTOR在调节免疫反应中的作用不断扩大

IF 32.4 1区医学

Immunity Pub Date : 2025-06-30 DOI: 10.1016/j.immuni.2025.06.010

Chirag H. Patel, Jonathan D. Powell

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