Immunity最新文献_第2页

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

引用次数: 0

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

引用次数: 0

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}

引用次数: 0

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

引用次数: 0

Mutant p53 exploits enhancers to elevate immunosuppressive chemokine expression and impair immune checkpoint inhibitors in pancreatic cancer 突变型p53利用增强子在胰腺癌中提高免疫抑制趋化因子的表达并损害免疫检查点抑制剂

IF 32.4 1区医学

Immunity Pub Date : 2025-06-30 DOI: 10.1016/j.immuni.2025.06.005

Dig B. Mahat, Heena Kumra, Sarah A. Castro, Emily Metcalf, Kim Nguyen, Ryo Morisue, William W. Ho, Ivy Chen, Brandon Sullivan, Leon H. Yim, Arundeep Singh, Jiayu Fu, Sean K. Waterton, Yu-Chi Cheng, Enrico Moiso, Vikash P. Chauhan, Hernandez Moura Silva, Stefani Spranger, Rakesh K. Jain, Phillip A. Sharp

{"title":"Mutant p53 exploits enhancers to elevate immunosuppressive chemokine expression and impair immune checkpoint inhibitors in pancreatic cancer","authors":"Dig B. Mahat, Heena Kumra, Sarah A. Castro, Emily Metcalf, Kim Nguyen, Ryo Morisue, William W. Ho, Ivy Chen, Brandon Sullivan, Leon H. Yim, Arundeep Singh, Jiayu Fu, Sean K. Waterton, Yu-Chi Cheng, Enrico Moiso, Vikash P. Chauhan, Hernandez Moura Silva, Stefani Spranger, Rakesh K. Jain, Phillip A. Sharp","doi":"10.1016/j.immuni.2025.06.005","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.06.005","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer characterized by activating KRAS mutations and TP53 alterations. TP53 missense mutations lose their wild-type tumor-suppressor function. Here, we studied whether p53 missense mutations have potential gain-of-function oncogenic roles and their impact on cancer-cell-intrinsic gene expression and the tumor immune microenvironment (TME) in PDAC. p53R172H established an immunosuppressive TME and impaired the efficacy of immune checkpoint inhibitors (ICIs) by regulating a distinct set of chemokines. Among these, tumor-specific reduction of Cxcl1, which encodes a chemoattractant for neutrophils, promoted T cell infiltration and decreased tumor growth. Mechanistically, p53R172H occupied the distal enhancers of Cxcl1 and amplified its expression. These enhancers were responsible for Cxcl1 expression and were essential for its immunosuppressive function. Nuclear factor κB (NF-κB) was a critical cofactor required for p53R172H occupancy at these enhancers. Thus, a common mutation in a tumor-suppressor transcription factor appropriates enhancers, thereby stimulating chemokine expression and establishing an immunosuppressive TME that diminishes ICI efficacy in PDAC.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"46 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516214","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 complex IV remodeling in tumor-associated macrophages amplifies interferon signaling and promotes anti-tumor immunity 肿瘤相关巨噬细胞线粒体复合体IV重塑放大干扰素信号并促进抗肿瘤免疫

IF 32.4 1区医学

Immunity Pub Date : 2025-06-30 DOI: 10.1016/j.immuni.2025.06.006

Megan L. Clark, Kamen P. Simeonov, Walter K. Mowel, Michaël F. Michieletto, Leonel Joannas, Jasmine M. Wright, Isabel Erickson, Lexus R. Johnson, Rakesh Krishnan, César de la Fuente-Núñez, Andy J. Minn, Jorge Henao-Mejia

{"title":"Mitochondrial complex IV remodeling in tumor-associated macrophages amplifies interferon signaling and promotes anti-tumor immunity","authors":"Megan L. Clark, Kamen P. Simeonov, Walter K. Mowel, Michaël F. Michieletto, Leonel Joannas, Jasmine M. Wright, Isabel Erickson, Lexus R. Johnson, Rakesh Krishnan, César de la Fuente-Núñez, Andy J. Minn, Jorge Henao-Mejia","doi":"10.1016/j.immuni.2025.06.006","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.06.006","url":null,"abstract":"Tumor-associated macrophages (TAMs) influence tumor progression and immune checkpoint blockade (ICB) efficacy. Interferon (IFN)-TAMs predict better survival and ICB responses, yet the mechanisms governing IFN-TAMs remain unclear. Here, we identify NDUFA4, a complex IV subunit of the electron transport chain, as a functional switch controlling TAM function and anti-tumor immunity. NDUFA4 expression sustained pro-tumoral TAMs. However, intratumoral IFNs decreased NDUFA4 expression in TAMs via the cooperative action of NDUFA4L3 and miR-147, co-encoded by a conserved bifunctional transcript. Mechanistically, NDUFA4 repression increased mitochondrial DNA release into the cytoplasm and subsequent STING activation, thereby amplifying anti-tumor IFN-induced transcriptional programs in TAMs. Finally, we designed RNA-based therapeutics that leveraged the specificity of miR-147 for the Ndufa4 transcript to enhance ICB efficacy and inhibit B16 melanoma tumor growth. These findings uncover mitochondrial complex IV remodeling as a critical mechanism governing the functional adaptation of macrophages to distinct microenvironments with broad implications for immunotherapy.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"10 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516213","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

Optogenetic vagal nerve stimulation attenuates heart failure by limiting the generation f monocyte-derived inflammatory CCRL2+ macrophages 光遗传迷走神经刺激通过限制单核细胞来源的炎性CCRL2+巨噬细胞的产生来减轻心力衰竭

IF 32.4 1区医学

Immunity Pub Date : 2025-06-27 DOI: 10.1016/j.immuni.2025.06.003

Guoqi Li, Congcong Zhang, Yang Li, Jie Yang, Jianing Wu, Yihui Shao, Ke Ma, Xinyu Zhang, Shuolin Zhu, Jie Du, Xin-Liang Ma, Liping Wang, Zhuofeng Lin, Ping Li, Yulin Li

{"title":"Optogenetic vagal nerve stimulation attenuates heart failure by limiting the generation f monocyte-derived inflammatory CCRL2+ macrophages","authors":"Guoqi Li, Congcong Zhang, Yang Li, Jie Yang, Jianing Wu, Yihui Shao, Ke Ma, Xinyu Zhang, Shuolin Zhu, Jie Du, Xin-Liang Ma, Liping Wang, Zhuofeng Lin, Ping Li, Yulin Li","doi":"10.1016/j.immuni.2025.06.003","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.06.003","url":null,"abstract":"Parasympathetic neuronal dysfunction is associated with heart failure (HF), yet the underlying mechanism is poorly understood. Here, we report that targeted vagal nerve stimulation (VNS) using optogenetics attenuated cardiac remodeling and HF induced by pressure overload. Unbiased approaches revealed that VNS decreased the proportion of Ccrl2+ macrophages, which were derived from myeloid monocytes and exhibited a distinct tumor necrosis factor alpha (TNF-α) cytokine-responsive, pro-hypertrophic, and profibrotic signature. Elimination of Ccrl2+ macrophages prevented cardiac remodeling and HF. Ccrl2+-macrophage-specific overexpression or global genetic loss of α7 nicotinic acetylcholine receptor (α7nAChR) highlighted their crucial contribution to VNS-mediated cardioprotection. Activation of α7nAChR inhibited Ccrl2+ macrophages’ TNF-α responsiveness through increased expression of the transcription factor NRF2. Cardiac Ccrl2+ macrophages and TNF-α-responsive proteins positively correlated with cardiac remodeling and dysfunction in humans. An α7nAChR agonist effectively blocked the development of HF. These results suggest that the vagal neuroimmune axis modulates HF and is a promising target for treatment.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"47 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516236","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

Diet-derived LPS determines intestinal IgA induction and repertoire characteristics independently of the microbiota 饮食来源的LPS决定了肠道IgA诱导和菌群特征，而不依赖于微生物群

IF 32.4 1区医学

Immunity Pub Date : 2025-06-26 DOI: 10.1016/j.immuni.2025.05.024

Catherine Mooser, Francesca Ronchi, Julien P. Limenitakis, Cristina Kalbermatter, Sandro Christensen, Mercedes Gomez de Agüero, Tobias Fuhrer, Uwe Sauer, Andrew J. Macpherson, Stephanie C. Ganal-Vonarburg

{"title":"Diet-derived LPS determines intestinal IgA induction and repertoire characteristics independently of the microbiota","authors":"Catherine Mooser, Francesca Ronchi, Julien P. Limenitakis, Cristina Kalbermatter, Sandro Christensen, Mercedes Gomez de Agüero, Tobias Fuhrer, Uwe Sauer, Andrew J. Macpherson, Stephanie C. Ganal-Vonarburg","doi":"10.1016/j.immuni.2025.05.024","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.05.024","url":null,"abstract":"A hallmark of the main secreted antibody immunoglobulin A (IgA) is its mutational load that accumulates throughout life. Although this is mainly interpreted in terms of continuing microbial induction, we show that dietary composition during early life can promote IgA induction, its repertoire, and mutational diversification independently of microbial exposure. Using germ-free and colonized mice fed different diets formulated with proprietary grain-based processing or from purified chemicals with different principal macronutrient calorie sources, we found that dietary lipopolysaccharide contamination led to Toll-like receptor (TLR) 4 signaling and promoted germinal center activity in the intestinal immune compartment. The effects of lipopolysaccharide on mucosal immune induction were phenocopied only when presented within colloidal liposomes rather than in dispersed solution. These findings indicate that dietary composition and its formulation can leave a durable impression on the resultant IgA repertoire.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"58 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488377","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

DOCK8 in T cells promotes Th17 and Treg cell functionality to restrain mucosal mast cells and limit susceptibility to oral anaphylaxis T细胞中的DOCK8促进Th17和Treg细胞功能抑制粘膜肥大细胞并限制对口腔过敏反应的易感性

IF 32.4 1区医学

Immunity Pub Date : 2025-06-25 DOI: 10.1016/j.immuni.2025.06.004

Erin Janssen, Mrinmoy Das, Jordan Butts, Mohammed Alasharee, Saikat Mukherjee, Gabriel L. Lozano, Chitong Rao, Andrew F. Livingston, Brian Woods, Emma Smith, Zachary Peters, Elena Milin, Maria A. Beamer, Hazel Wilkie, Juan-Manuel Leyva-Castillo, Christy Kam, Ali Sobh, Majed Dasouki, Rima Hanna Wakim, Ghassan Dbaibo, Raif S. Geha

{"title":"DOCK8 in T cells promotes Th17 and Treg cell functionality to restrain mucosal mast cells and limit susceptibility to oral anaphylaxis","authors":"Erin Janssen, Mrinmoy Das, Jordan Butts, Mohammed Alasharee, Saikat Mukherjee, Gabriel L. Lozano, Chitong Rao, Andrew F. Livingston, Brian Woods, Emma Smith, Zachary Peters, Elena Milin, Maria A. Beamer, Hazel Wilkie, Juan-Manuel Leyva-Castillo, Christy Kam, Ali Sobh, Majed Dasouki, Rima Hanna Wakim, Ghassan Dbaibo, Raif S. Geha","doi":"10.1016/j.immuni.2025.06.004","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.06.004","url":null,"abstract":"Immunoglobulin E (IgE)-mediated release of mediators from mast cells (MCs) drives food allergy, and intestinal MC load is an important determinant of disease severity. Dedicator of cytokinesis 8 (DOCK8)-deficient patients are highly susceptible to food allergy. We found that they exhibited elevated serum MC tryptase levels, suggesting increased MC load. Dock8−/− mice also had exaggerated IgE-mediated oral anaphylaxis, expansion of jejunal mucosal MCs (MMCs), and elevated serum levels of MMC-derived tryptase. This resulted in increased intestinal permeability, which promoted antigen absorption and thereby oral anaphylaxis. Mechanistically, these events were driven by an intestinal cascade in which reduced interleukin (IL)-17 cytokines led to dysbiosis, which drove IL-25 production. Increased IL-25 enhanced T helper (Th)2 production of IL-4 that expanded MMCs and exaggerated oral anaphylaxis. Furthermore, the failure of DOCK8-deficient T regulatory (Treg) cells to suppress intestinal IL-4 production and MC expansion left the exaggerated anaphylaxis unrestrained. These results suggest multi-faceted coordination between the microbiome, mucosal T cells, and MCs to restrict oral anaphylaxis.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"37 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479515","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