Science Immunology最新文献_第2页

PPARβ/δ-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8+ T cells PPARβ/δ-orchestrated 代谢重编程支持记忆 CD8+ T 细胞的形成和维持。

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Science Immunology Pub Date : 2024-08-23 DOI: 10.1126/sciimmunol.adn2717

Alessio Bevilacqua, Fabien Franco, Ya-Ting Lu, Nabil Rahiman, Kung-Chi Kao, Yu-Ming Chuang, Yanan Zhu, Werner Held, Xin Xie, Kristin C. Gunsalus, Zhengtao Xiao, Shih-Yu Chen, Ping-Chih Ho

{"title":"PPARβ/δ-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8+ T cells","authors":"Alessio Bevilacqua, Fabien Franco, Ya-Ting Lu, Nabil Rahiman, Kung-Chi Kao, Yu-Ming Chuang, Yanan Zhu, Werner Held, Xin Xie, Kristin C. Gunsalus, Zhengtao Xiao, Shih-Yu Chen, Ping-Chih Ho","doi":"10.1126/sciimmunol.adn2717","DOIUrl":"10.1126/sciimmunol.adn2717","url":null,"abstract":"<div >The formation of memory T cells is a fundamental feature of adaptative immunity, allowing the establishment of long-term protection against pathogens. Although emerging evidence suggests that metabolic reprogramming is crucial for memory T cell differentiation and survival, the underlying mechanisms that drive metabolic rewiring in memory T cells remain unclear. Here, we found that up-regulation of the nuclear receptor peroxisome proliferator–activated receptor β/δ (PPARβ/δ) instructs the metabolic reprogramming that occurs during the establishment of central memory CD8<sup>+</sup> T cells. PPARβ/δ-regulated changes included suppression of aerobic glycolysis and enhancement of oxidative metabolism and fatty acid oxidation. Mechanistically, exposure to interleukin-15 and expression of T cell factor 1 facilitated activation of the PPARβ/δ pathway, counteracting apoptosis induced by antigen clearance and metabolic stress. Together, our findings indicate that PPARβ/δ is a master metabolic regulator orchestrating a metabolic switch that may be favorable for T cell longevity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":17.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044165","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

Hematopoietic stem cell heterogeneity and age-associated platelet bias are evolutionarily conserved 造血干细胞异质性和与年龄相关的血小板偏向在进化过程中是保守的。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-23 DOI: 10.1126/sciimmunol.adk3469

Merve Aksöz, Grigore-Aristide Gafencu, Bilyana Stoilova, Mario Buono, Ying Zhang, Sven Turkalj, Yiran Meng, Niels Asger Jakobsen, Marlen Metzner, Sally-Ann Clark, Ryan Beveridge, Supat Thongjuea, Paresh Vyas, Claus Nerlov

{"title":"Hematopoietic stem cell heterogeneity and age-associated platelet bias are evolutionarily conserved","authors":"Merve Aksöz, Grigore-Aristide Gafencu, Bilyana Stoilova, Mario Buono, Ying Zhang, Sven Turkalj, Yiran Meng, Niels Asger Jakobsen, Marlen Metzner, Sally-Ann Clark, Ryan Beveridge, Supat Thongjuea, Paresh Vyas, Claus Nerlov","doi":"10.1126/sciimmunol.adk3469","DOIUrl":"10.1126/sciimmunol.adk3469","url":null,"abstract":"<div >Hematopoietic stem cells (HSCs) reconstitute multilineage human hematopoiesis after clinical bone marrow (BM) transplantation and are the cells of origin of some hematological malignancies. Although HSCs provide multilineage engraftment, individual murine HSCs are lineage biased and contribute unequally to blood cell lineages. Here, we performed high-throughput single-cell RNA sequencing in mice after xenograft with molecularly barcoded adult human BM HSCs. We demonstrated that human individual BM HSCs are also functionally and transcriptionally lineage biased. Specifically, we identified platelet-biased and multilineage human HSCs. Quantitative comparison of transcriptomes from single HSCs from young and aged BM showed that both the proportion of platelet-biased HSCs and their level of transcriptional platelet priming increase with age. Therefore, platelet-biased HSCs and their increased prevalence and transcriptional platelet priming during aging are conserved features of mammalian evolution.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":17.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044163","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

Mast cell–derived BH4 and serotonin are critical mediators of postoperative pain 肥大细胞衍生的 BH4 和血清素是术后疼痛的关键介质。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-23 DOI: 10.1126/sciimmunol.adh0545

Philipp Starkl, Gustav Jonsson, Tyler Artner, Bruna Lenfers Turnes, Laura-Marie Gail, Tiago Oliveira, Aakanksha Jain, Nadine Serhan, Karel Stejskal, Karin Lakovits, Anastasiya Hladik, Meilin An, Keith M. Channon, Hail Kim, Thomas Köcher, Wolfgang Weninger, Georg Stary, Sylvia Knapp, Victoria Klang, Nicolas Gaudenzio, Clifford J. Woolf, Shweta Tikoo, Rohit Jain, Josef M. Penninger, Shane J. F. Cronin

{"title":"Mast cell–derived BH4 and serotonin are critical mediators of postoperative pain","authors":"Philipp Starkl, Gustav Jonsson, Tyler Artner, Bruna Lenfers Turnes, Laura-Marie Gail, Tiago Oliveira, Aakanksha Jain, Nadine Serhan, Karel Stejskal, Karin Lakovits, Anastasiya Hladik, Meilin An, Keith M. Channon, Hail Kim, Thomas Köcher, Wolfgang Weninger, Georg Stary, Sylvia Knapp, Victoria Klang, Nicolas Gaudenzio, Clifford J. Woolf, Shweta Tikoo, Rohit Jain, Josef M. Penninger, Shane J. F. Cronin","doi":"10.1126/sciimmunol.adh0545","DOIUrl":"10.1126/sciimmunol.adh0545","url":null,"abstract":"<div >Postoperative pain affects most patients after major surgery and can transition to chronic pain. The considerable side effects and limited efficacy of current treatments underline the need for new therapeutic options. We observed increased amounts of the metabolites BH4 and serotonin after skin injury. Mast cells were primary postoperative sources of <i>Gch1</i>, the rate-limiting enzyme in BH4 synthesis, itself an obligate cofactor in serotonin production by tryptophan hydroxylase (Tph1). Mice deficient in mast cells or in mast cell–specific <i>Gch1</i> or <i>Tph1</i> showed drastically decreased postoperative pain. We found that injury induced the nociceptive neuropeptide substance P, mast cell degranulation, and granule nerve colocalization. Substance P triggered serotonin release in mouse and human mast cells, and substance P receptor blockade substantially ameliorated pain hypersensitivity. Our findings highlight the importance of mast cells at the neuroimmune interface and substance P–driven mast cell BH4 and serotonin production as a therapeutic target for postoperative pain treatment.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":17.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044164","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

Context-dependent role of group 3 innate lymphoid cells in mucosal protection 第 3 组先天性淋巴细胞在粘膜保护中的作用与环境有关。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-16 DOI: 10.1126/sciimmunol.ade7530

Leandro P. Araujo, Madeline Edwards, Koichiro Irie, Yiming Huang, Yoshinaga Kawano, Alexander Tran, Simona De Michele, Govind Bhagat, Harris H. Wang, Ivaylo I. Ivanov

{"title":"Context-dependent role of group 3 innate lymphoid cells in mucosal protection","authors":"Leandro P. Araujo, Madeline Edwards, Koichiro Irie, Yiming Huang, Yoshinaga Kawano, Alexander Tran, Simona De Michele, Govind Bhagat, Harris H. Wang, Ivaylo I. Ivanov","doi":"10.1126/sciimmunol.ade7530","DOIUrl":"10.1126/sciimmunol.ade7530","url":null,"abstract":"<div >How group 3 innate lymphoid cells (ILC3s) regulate mucosal protection in the presence of T cells remains poorly understood. Here, we examined ILC3 function in intestinal immunity using ILC3-deficient mice that maintain endogenous T cells, T helper 17 (T<sub>H</sub>17) cells, and secondary lymphoid organs. ILC3s were dispensable for generation of T<sub>H</sub>17 and T<sub>H</sub>22 cell responses to commensal and pathogenic bacteria, and absence of ILC3s did not affect IL-22 production by CD4 T cells before or during infection. However, despite the presence of IL-22–producing T cells, ILC3s and ILC3-derived IL-22 were required for maintaining homeostatic functions of the intestinal epithelium. T cell–sufficient, ILC3-deficient mice were capable of pathogen clearance and survived infection with a low dose of <i>Citrobacter rodentium</i>. However, ILC3s promoted pathogen tolerance at early time points of infection by activating tissue-protective immune pathways. Consequently, ILC3s were indispensable for survival after high-dose infection. Our results demonstrate a context-dependent role for ILC3s in immune-sufficient animals and provide a blueprint for uncoupling of ILC3 and T<sub>H</sub>17 cell functions.</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":"141992387","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

Erratum for the Research Article “SARS-CoV-2 inflammation durably imprints memory CD4 T cells” by S. L. Gray-Gaillard et al. S. L. Gray-Gaillard 等人的研究文章 "SARS-CoV-2 炎症对记忆 CD4 T 细胞的持久影响 "的勘误。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-08-16 DOI: 10.1126/sciimmunol.adr9665

引用次数: 0

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}

引用次数: 0

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

引用次数: 0

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

引用次数: 0

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}

引用次数: 0

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}

引用次数: 0