Science Immunology最新文献_第5页

Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities 先天性免疫错误和代谢基因的功能重叠决定了 T 细胞代谢的脆弱性

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-16 DOI: 10.1126/sciimmunol.adh0368

Andrew R. Patterson, Gabriel A. Needle, Ayaka Sugiura, Erin Q. Jennings, Channing Chi, KayLee K. Steiner, Emilie L. Fisher, Gabriella L. Robertson, Caroline Bodnya, Janet G. Markle, Ryan D. Sheldon, Russell G. Jones, Vivian Gama, Jeffrey C. Rathmell

{"title":"Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities","authors":"Andrew R. Patterson, Gabriel A. Needle, Ayaka Sugiura, Erin Q. Jennings, Channing Chi, KayLee K. Steiner, Emilie L. Fisher, Gabriella L. Robertson, Caroline Bodnya, Janet G. Markle, Ryan D. Sheldon, Russell G. Jones, Vivian Gama, Jeffrey C. Rathmell","doi":"10.1126/sciimmunol.adh0368","DOIUrl":"10.1126/sciimmunol.adh0368","url":null,"abstract":"<div >Inborn errors of metabolism (IEMs) and immunity (IEIs) are Mendelian diseases in which complex phenotypes and patient rarity have limited clinical understanding. Whereas few genes have been annotated as contributing to both IEMs and IEIs, immunometabolic demands suggested greater functional overlap. Here, CRISPR screens tested IEM genes for immunologic roles and IEI genes for metabolic effects and found considerable previously unappreciated crossover. Analysis of IEMs showed that N-linked glycosylation and the hexosamine pathway enzyme <i>Gfpt1</i> are critical for T cell expansion and function. Further, T helper (T<sub>H</sub>1) cells synthesized uridine diphosphate <i>N</i>-acetylglucosamine more rapidly and were more impaired by <i>Gfpt1</i> deficiency than T<sub>H</sub>17 cells. Screening IEI genes found that <i>Bcl11b</i> promotes the CD4 T cell mitochondrial activity and <i>Mcl1</i> expression necessary to prevent metabolic stress. Thus, a high degree of functional overlap exists between IEM and IEI genes, and immunometabolic mechanisms may underlie a previously underappreciated intersection of these disorders.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":17.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992052","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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Erratum for the Research Article “TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf” by Y. Chang et al. Y. Chang 等人的研究文章 "TGF-β 通过 c-Maf 指定小鼠 CD4+ T 细胞中 TFH 与 TH17 细胞的命运 "的勘误。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-09 DOI: 10.1126/sciimmunol.adr7181

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SARS-CoV-2 JN.1 variant evasion of IGHV3-53/3-66 B cell germlines SARS-CoV-2 JN.1 变体对 IGHV3-53/3-66 B 细胞种系的规避。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-09 DOI: 10.1126/sciimmunol.adp9279

Ida Paciello, Giuseppe Maccari, Giulio Pierleoni, Federica Perrone, Giulia Realini, Marco Troisi, Gabriele Anichini, Maria Grazia Cusi, Rino Rappuoli, Emanuele Andreano

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B cells require DOCK8 to elicit and integrate T cell help when antigen is limiting 当抗原具有局限性时，B 细胞需要 DOCK8 来激发和整合 T 细胞的帮助。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-09 DOI: 10.1126/sciimmunol.add4874

Mukta Deobagkar-Lele, Greg Crawford, Tanya L. Crockford, Jennifer Back, Rose Hodgson, Aneesha Bhandari, Katherine R. Bull, Richard J. Cornall

{"title":"B cells require DOCK8 to elicit and integrate T cell help when antigen is limiting","authors":"Mukta Deobagkar-Lele, Greg Crawford, Tanya L. Crockford, Jennifer Back, Rose Hodgson, Aneesha Bhandari, Katherine R. Bull, Richard J. Cornall","doi":"10.1126/sciimmunol.add4874","DOIUrl":"10.1126/sciimmunol.add4874","url":null,"abstract":"<div >Dedicator of cytokinesis 8 (DOCK8) immunodeficiency syndrome is characterized by a failure of the germinal center response, a process involving the proliferation and positive selection of antigen-specific B cells. Here, we describe how DOCK8-deficient B cells are blocked at a light-zone checkpoint in the germinal centers of immunized mice, where they are unable to respond to T cell–dependent survival and selection signals and consequently differentiate into plasma cells or memory B cells. Although DOCK8-deficient B cells can acquire and present antigen to initiate activation of cognate T cells, integrin up-regulation, B cell–T cell conjugate formation, and costimulation are insufficient for sustained B cell and T cell activation when antigen availability is limited. Our findings provide an explanation for the failure of the humoral response in DOCK8 immunodeficiency syndrome and insight into how the level of available antigen modulates B cell–T cell cross-talk to fine-tune humoral immune responses and immunological memory.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":17.6,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141910108","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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The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity 埃及伊蚊唾液免疫抑制因子以人类 CD47 检查点为靶点，增强了虫媒病毒的皮肤传染性。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-09 DOI: 10.1126/sciimmunol.adk9872

Alejandro Marin-Lopez, John D. Huck, Allen T. Esterly, Veronica Azcutia, Connor Rosen, Rolando Garcia-Milian, Esen Sefik, Gemma Vidal-Pedrola, Hamidah Raduwan, Tse-Yu Chen, Gunjan Arora, Stephanie Halene, Albert C. Shaw, Noah W. Palm, Richard A. Flavell, Charles A. Parkos, Saravanan Thangamani, Aaron M. Ring, Erol Fikrig

{"title":"The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity","authors":"Alejandro Marin-Lopez, John D. Huck, Allen T. Esterly, Veronica Azcutia, Connor Rosen, Rolando Garcia-Milian, Esen Sefik, Gemma Vidal-Pedrola, Hamidah Raduwan, Tse-Yu Chen, Gunjan Arora, Stephanie Halene, Albert C. Shaw, Noah W. Palm, Richard A. Flavell, Charles A. Parkos, Saravanan Thangamani, Aaron M. Ring, Erol Fikrig","doi":"10.1126/sciimmunol.adk9872","DOIUrl":"10.1126/sciimmunol.adk9872","url":null,"abstract":"<div >The <i>Aedes aegypti</i> mosquito is a vector of many infectious agents, including flaviviruses such as Zika virus. Components of mosquito saliva have pleomorphic effects on the vertebrate host to enhance blood feeding, and these changes also create a favorable niche for pathogen replication and dissemination. Here, we demonstrate that human CD47, which is known to be involved in various immune processes, interacts with a 34-kilodalton mosquito salivary protein named Nest1. Nest1 is up-regulated in blood-fed female <i>A. aegypti</i> and facilitates Zika virus dissemination in human skin explants. Nest1 has a stronger affinity for CD47 than its natural ligand, signal regulatory protein α, competing for binding at the same interface. The interaction between Nest1 with CD47 suppresses phagocytosis by human macrophages and inhibits proinflammatory responses by white blood cells, thereby suppressing antiviral responses in the skin. This interaction elucidates how an arthropod protein alters the human response to promote arbovirus infectivity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":17.6,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141910111","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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cGAS-activated endothelial cell–T cell cross-talk initiates tertiary lymphoid structure formation cGAS 激活的内皮细胞-T 细胞交叉对话启动了三级淋巴结构的形成。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-02 DOI: 10.1126/sciimmunol.adk2612

Ruibo Zhao, Jinghe Zhang, Jialu Ma, Yali Qu, Zhenrong Yang, Zhinan Yin, Fengyin Li, Zhongjun Dong, Qinmiao Sun, Shu Zhu, Zhijian J. Chen, Daxing Gao

{"title":"cGAS-activated endothelial cell–T cell cross-talk initiates tertiary lymphoid structure formation","authors":"Ruibo Zhao, Jinghe Zhang, Jialu Ma, Yali Qu, Zhenrong Yang, Zhinan Yin, Fengyin Li, Zhongjun Dong, Qinmiao Sun, Shu Zhu, Zhijian J. Chen, Daxing Gao","doi":"10.1126/sciimmunol.adk2612","DOIUrl":"10.1126/sciimmunol.adk2612","url":null,"abstract":"<div >Aberrant activation of the cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes (cGAS-STING) pathway causes autoimmunity in humans and mice; however, the exact mechanism by which the cGAS-STING pathway initiates adaptive immunity and tissue pathology is still not fully understood. Here, we used a cGAS knockin (KI) mouse model that develops systemic autoimmunity. In the lungs of cGAS-KI mice, blood vessels were enclosed by organized lymphoid tissues that resemble tertiary lymphoid structures (TLSs). Cell-intrinsic cGAS induction promoted up-regulation of CCR5 in CD8<sup>+</sup> T cells and led to CCL5 production in vascular endothelial cells. Peripheral CD8<sup>+</sup> T cells were recruited to the lungs and produced CXCL13 and interferon-γ. The latter triggered endothelial cell death, potentiated CCL5 production, and was essential for TLS establishment. Blocking CCL5 or CCR5, or depleting CD8<sup>+</sup> T cells, impaired TLS formation. cGAS-mediated TLS formation also enhanced humoral and antitumor responses. These data demonstrate that cGAS signaling drives a specialized lymphoid structure that underlies autoimmune tissue pathology.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":17.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adk2612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Recruited atypical Ly6G+ macrophages license alveolar regeneration after lung injury 肺损伤后招募的非典型 Ly6G+ 巨噬细胞许可肺泡再生

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-02 DOI: 10.1126/sciimmunol.ado1227

Cecilia Ruscitti, Joan Abinet, Pauline Maréchal, Margot Meunier, Constance de Meeûs, Domien Vanneste, Pierre Janssen, Mickael Dourcy, Marc Thiry, Fabrice Bureau, Christoph Schneider, Benedicte Machiels, Andres Hidalgo, Florent Ginhoux, Benjamin G. Dewals, Julien Guiot, Florence Schleich, Mutien-Marie Garigliany, Akeila Bellahcène, Coraline Radermecker, Thomas Marichal

{"title":"Recruited atypical Ly6G+ macrophages license alveolar regeneration after lung injury","authors":"Cecilia Ruscitti, Joan Abinet, Pauline Maréchal, Margot Meunier, Constance de Meeûs, Domien Vanneste, Pierre Janssen, Mickael Dourcy, Marc Thiry, Fabrice Bureau, Christoph Schneider, Benedicte Machiels, Andres Hidalgo, Florent Ginhoux, Benjamin G. Dewals, Julien Guiot, Florence Schleich, Mutien-Marie Garigliany, Akeila Bellahcène, Coraline Radermecker, Thomas Marichal","doi":"10.1126/sciimmunol.ado1227","DOIUrl":"10.1126/sciimmunol.ado1227","url":null,"abstract":"<div >The lung is constantly exposed to airborne pathogens and particles that can cause alveolar damage. Hence, appropriate repair responses are essential for gas exchange and life. Here, we deciphered the spatiotemporal trajectory and function of an atypical population of macrophages after lung injury. Post–influenza A virus (IAV) infection, short-lived monocyte-derived Ly6G-expressing macrophages (Ly6G<sup>+</sup> Macs) were recruited to the alveoli of lung perilesional areas. Ly6G<sup>+</sup> Macs engulfed immune cells, exhibited a high metabolic potential, and clustered with alveolar type 2 epithelial cells (AT2s) in zones of active epithelial regeneration. Ly6G<sup>+</sup> Macs were partially dependent on granulocyte-macrophage colony-stimulating factor and interleukin-4 receptor signaling and were essential for AT2-dependent alveolar regeneration. Similar macrophages were recruited in other models of injury and in the airspaces of lungs from patients with suspected pneumonia. This study identifies perilesional alveolar Ly6G<sup>+</sup> Macs as a spatially restricted, short-lived macrophage subset promoting epithelial regeneration postinjury, thus representing an attractive therapeutic target for treating lung damage.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":17.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879346","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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Enough already: T cell inflammation and SARS-CoV-2 virus persist in Long Covid 已经够了T 细胞炎症和 SARS-CoV-2 病毒在 Long Covid 持续存在。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-02 DOI: 10.1126/sciimmunol.adr9661

Rachael A. Clark

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The yeast also rises! PD-L1 dampens inflammation linked to fungal infections 酵母菌也会上升！PD-L1 可抑制与真菌感染有关的炎症。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-02 DOI: 10.1126/sciimmunol.adr9663

Sultan AlSalem, Shiv Pillai

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Never trust a single myeloid marker: Ly6G on repair-promoting lung macrophages 永远不要相信单一的骨髓标志物促进修复的肺巨噬细胞上的 Ly6G。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-02 DOI: 10.1126/sciimmunol.adq7306

Chrysante S. Iliakis, Andreas Wack

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