Immunity最新文献_第10页

A cis-regulatory element controls expression of histone deacetylase 9 to fine-tune inflammasome-dependent chronic inflammation in atherosclerosis 一种顺式调控元件控制组蛋白去乙酰化酶9的表达，以微调动脉粥样硬化中炎性小体依赖性慢性炎症

IF 32.4 1区医学

Immunity Pub Date : 2025-01-28 DOI: 10.1016/j.immuni.2025.01.003

Yaw Asare, Guangyao Yan, Christina Schlegl, Matthias Prestel, Emiel P.C. van der Vorst, Abraham J.P. Teunissen, Arailym Aronova, Federica Tosato, Nawraa Naser, Julio Caputo, Geoffrey Prevot, Anthony Azzun, Benedikt Wefers, Wolfgang Wurst, Melanie Schneider, Ignasi Forne, Kiril Bidzhekov, Ronald Naumann, Sander W. van der Laan, Markus Brandhofer, Martin Dichgans

{"title":"A cis-regulatory element controls expression of histone deacetylase 9 to fine-tune inflammasome-dependent chronic inflammation in atherosclerosis","authors":"Yaw Asare, Guangyao Yan, Christina Schlegl, Matthias Prestel, Emiel P.C. van der Vorst, Abraham J.P. Teunissen, Arailym Aronova, Federica Tosato, Nawraa Naser, Julio Caputo, Geoffrey Prevot, Anthony Azzun, Benedikt Wefers, Wolfgang Wurst, Melanie Schneider, Ignasi Forne, Kiril Bidzhekov, Ronald Naumann, Sander W. van der Laan, Markus Brandhofer, Martin Dichgans","doi":"10.1016/j.immuni.2025.01.003","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.01.003","url":null,"abstract":"Common genetic variants in a conserved cis-regulatory element (CRE) at histone deacetylase (HDAC)9 are a major risk factor for cardiovascular disease, including stroke and coronary artery disease. Given the consistency of this association and its proinflammatory properties, we examined the mechanisms whereby HDAC9 regulates vascular inflammation. HDAC9 bound and mediated deacetylation of NLRP3 in the NACHT and LRR domains leading to inflammasome activation and lytic cell death. Targeted deletion of the critical CRE in mice increased Hdac9 expression in myeloid cells to exacerbate inflammasome-dependent chronic inflammation. In human carotid endarterectomy samples, increased HDAC9 expression was associated with atheroprogression and clinical plaque instability. Incorporation of TMP195, a class IIa HDAC inhibitor, into lipoprotein-based nanoparticles to target HDAC9 at the site of myeloid-driven vascular inflammation stabilized atherosclerotic plaques, implying a lower risk of plaque rupture and cardiovascular events. Our findings link HDAC9 to atherogenic inflammation and provide a paradigm for anti-inflammatory therapeutics for atherosclerosis.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"45 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049950","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

Spatially restricted and ontogenically distinct hepatic macrophages are required for tissue repair 组织修复需要空间限制和不同的肝巨噬细胞

IF 32.4 1区医学

Immunity Pub Date : 2025-01-24 DOI: 10.1016/j.immuni.2025.01.002

Federico F. De Ponti, Anna Bujko, Zhuangzhuang Liu, Paul J. Collins, Sara Schuermans, Christian Maueroder, Seraja Amstelveen, Tinne Thoné, Liesbet Martens, John G. McKendrick, Pieter A. Louwe, Ana Sànchez Cruz, Wouter Saelens, Kylie P. Matchett, Kathryn J. Waller, Christian Zwicker, Aimée Buglar-Lamb, Bavo Vanneste, Fleur Parmentier, Mushida Binte Abdul Latib, Charlotte L. Scott

{"title":"Spatially restricted and ontogenically distinct hepatic macrophages are required for tissue repair","authors":"Federico F. De Ponti, Anna Bujko, Zhuangzhuang Liu, Paul J. Collins, Sara Schuermans, Christian Maueroder, Seraja Amstelveen, Tinne Thoné, Liesbet Martens, John G. McKendrick, Pieter A. Louwe, Ana Sànchez Cruz, Wouter Saelens, Kylie P. Matchett, Kathryn J. Waller, Christian Zwicker, Aimée Buglar-Lamb, Bavo Vanneste, Fleur Parmentier, Mushida Binte Abdul Latib, Charlotte L. Scott","doi":"10.1016/j.immuni.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.01.002","url":null,"abstract":"Our understanding of the functional heterogeneity of resident versus recruited macrophages in the diseased liver is limited. A population of recruited lipid-associated macrophages (LAMs) has been reported to populate the diseased liver alongside resident Kupffer cells (KCs). However, the precise roles of these distinct macrophage subsets remain elusive. Here, using proteogenomics, we have identified LAMs in multiple models of liver injury. Moreover, we found that this phenotype is not specific to recruited macrophages, as a subset of resident KCs can also adopt a LAM-like phenotype in the mouse and human liver. By combining genetic mouse models targeting the distinct populations, we determined that both recruited LAMs and resident LAM-like KCs play crucial roles in tissue repair. Specifically, triggering receptor expressed on myeloid cells 2 (TREM2) expression on either resident or recruited macrophages is required for the efficient clearance of dying cells, enhancing repair and preventing exacerbated fibrosis.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"51 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026726","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

Microbiota translocation following intestinal barrier disruption promotes Mincle-mediated training of myeloid progenitors in the bone marrow 肠道屏障破坏后的微生物群易位促进了骨髓中髓系祖细胞的微颗粒介导的训练

IF 32.4 1区医学

Immunity Pub Date : 2025-01-22 DOI: 10.1016/j.immuni.2024.12.012

Iñaki Robles-Vera, Aitor Jarit-Cabanillas, Paola Brandi, María Martínez-López, Sarai Martínez-Cano, Manuel Rodrigo-Tapias, Marcos Femenía-Muiña, Ana Redondo-Urzainqui, Vanesa Nuñez, Cristina González-Correa, Javier Moleón, Juan Duarte, Laura Conejero, Pablo Mata-Martínez, Carmen María Díez-Rivero, Marta Bergón-Gutiérrez, Iván Fernández-López, Manuel J. Gómez, Ana Quintas, Ana Dopazo, David Sancho

{"title":"Microbiota translocation following intestinal barrier disruption promotes Mincle-mediated training of myeloid progenitors in the bone marrow","authors":"Iñaki Robles-Vera, Aitor Jarit-Cabanillas, Paola Brandi, María Martínez-López, Sarai Martínez-Cano, Manuel Rodrigo-Tapias, Marcos Femenía-Muiña, Ana Redondo-Urzainqui, Vanesa Nuñez, Cristina González-Correa, Javier Moleón, Juan Duarte, Laura Conejero, Pablo Mata-Martínez, Carmen María Díez-Rivero, Marta Bergón-Gutiérrez, Iván Fernández-López, Manuel J. Gómez, Ana Quintas, Ana Dopazo, David Sancho","doi":"10.1016/j.immuni.2024.12.012","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.12.012","url":null,"abstract":"Impairment of the intestinal barrier allows the systemic translocation of commensal bacteria, inducing a proinflammatory state in the host. Here, we investigated innate immune responses following increased gut permeability upon administration of dextran sulfate sodium (DSS) in mice. We found that Enterococcus faecalis translocated to the bone marrow following DSS treatment and induced trained immunity (TI) hallmarks in bone-marrow-derived mouse macrophages and human monocytes. DSS treatment or heat-killed E. faecalis reprogrammed bone marrow progenitors (BMPs), resulting in enhanced inflammatory responses in vitro and in vivo and protection against subsequent pathogen infections. The C-type lectin receptor Mincle (Clec4e) was essential for E. faecalis-induced TI in BMPs. Clec4e−/− mice showed impaired TI upon E. faecalis administration and reduced pathology following DSS treatment. Thus, Mincle sensing of E. faecalis induces TI that may have long-term effects on pathologies associated with increased gut permeability.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"46 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991969","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

CD4+ T cells re-wire granuloma cellularity and regulatory networks to promote immunomodulation following Mtb reinfection CD4+ T细胞重新连接肉芽肿细胞和调节网络，促进Mtb再感染后的免疫调节

IF 32.4 1区医学

Immunity Pub Date : 2025-01-15 DOI: 10.1016/j.immuni.2025.01.001

Joshua D. Bromley, Sharie Keanne C. Ganchua, Sarah K. Nyquist, Pauline Maiello, Michael Chao, H. Jacob Borish, Mark Rodgers, Jaime Tomko, Kara Kracinovsky, Douaa Mugahid, Son Nguyen, Qianchang Dennis Wang, Jacob M. Rosenberg, Edwin C. Klein, Hannah P. Gideon, Roisin Floyd-O’Sullivan, Bonnie Berger, Charles A. Scanga, Philana Ling Lin, Sarah M. Fortune, JoAnne L. Flynn

引用次数: 0

A triad of somatic mutagenesis converges in self-reactive B cells to cause a virus-induced autoimmune disease 三种体细胞突变在自身反应性B细胞中汇合，引起病毒诱导的自身免疫性疾病

IF 32.4 1区医学

Immunity Pub Date : 2025-01-15 DOI: 10.1016/j.immuni.2024.12.011

Clara Young, Mandeep Singh, Katherine J.L. Jackson, Matt A. Field, Timothy J. Peters, Stefano Angioletti-Uberti, Daan Frenkel, Shyamsundar Ravishankar, Money Gupta, Jing J. Wang, David Agapiou, Megan L. Faulks, Ghamdan Al-Eryani, Fabio Luciani, Tom P. Gordon, Joanne H. Reed, Mark Danta, Andrew Carr, Anthony D. Kelleher, Gregory J. Dore, Christopher C. Goodnow

{"title":"A triad of somatic mutagenesis converges in self-reactive B cells to cause a virus-induced autoimmune disease","authors":"Clara Young, Mandeep Singh, Katherine J.L. Jackson, Matt A. Field, Timothy J. Peters, Stefano Angioletti-Uberti, Daan Frenkel, Shyamsundar Ravishankar, Money Gupta, Jing J. Wang, David Agapiou, Megan L. Faulks, Ghamdan Al-Eryani, Fabio Luciani, Tom P. Gordon, Joanne H. Reed, Mark Danta, Andrew Carr, Anthony D. Kelleher, Gregory J. Dore, Christopher C. Goodnow","doi":"10.1016/j.immuni.2024.12.011","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.12.011","url":null,"abstract":"The unexplained association between infection and autoimmune disease is strongest for hepatitis C virus-induced cryoglobulinemic vasculitis (HCV-cryovas). To analyze its origins, we traced the evolution of pathogenic rheumatoid factor (RF) autoantibodies in four HCV-cryovas patients by deep single-cell multi-omic analysis, revealing three sources of B cell somatic mutation converged to drive the accumulation of a large disease-causing clone. A method for quantifying low-affinity binding revealed recurring antibody variable domain combinations created by V(D)J recombination that bound self-immunoglobulin G (IgG) but not viral E2 antigen. Whole-genome sequencing revealed thousands of somatic mutations, numerically comparable to chronic lymphocytic leukemia and normal memory B cells, but with 1–2 corresponding to driver mutations found recurrently in B cell leukemia and lymphoma. V(D)J hypermutation created autoantibodies with compromised solubility in complex with self-IgG. In this virus-induced autoimmune disease, infection promotes a catastrophic confluence of somatic mutagenesis in the descendants of a single B cell.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"118 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981690","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

Mitochondria and NLRP3: To die or inflame 线粒体和NLRP3：死亡或发炎

IF 32.4 1区医学

Immunity Pub Date : 2025-01-14 DOI: 10.1016/j.immuni.2024.12.007

Shuangshuang Yang, Guannan Huang, Jenny P.-Y. Ting

引用次数: 0

Gut know-how: IL-22 from T cells boosts stress resilience 肠道知识：来自T细胞的IL-22增强了压力恢复能力

IF 32.4 1区医学

Immunity Pub Date : 2025-01-14 DOI: 10.1016/j.immuni.2024.11.022

Ruodi Yang, Danyang He

引用次数: 0

Interleukin-17 and fat: Timing is everything 白细胞介素-17和脂肪：时机决定一切