Science Immunology最新文献_第4页

Functional differences between rodent and human PD-1 linked to evolutionary divergence 啮齿类动物和人类PD-1的功能差异与进化分化有关

IF 17.6 1区医学

Science Immunology Pub Date : 2025-01-03 DOI: 10.1126/sciimmunol.ads6295

Takeya Masubuchi, Lin Chen, Nimi Marcel, George A. Wen, Christine Caron, Jibin Zhang, Yunlong Zhao, Gerald P. Morris, Xu Chen, Stephen M. Hedrick, Li-Fan Lu, Chuan Wu, Zhengting Zou, Jack D. Bui, Enfu Hui

{"title":"Functional differences between rodent and human PD-1 linked to evolutionary divergence","authors":"Takeya Masubuchi, Lin Chen, Nimi Marcel, George A. Wen, Christine Caron, Jibin Zhang, Yunlong Zhao, Gerald P. Morris, Xu Chen, Stephen M. Hedrick, Li-Fan Lu, Chuan Wu, Zhengting Zou, Jack D. Bui, Enfu Hui","doi":"10.1126/sciimmunol.ads6295","DOIUrl":"10.1126/sciimmunol.ads6295","url":null,"abstract":"<div >Mechanistic understanding of the inhibitory immunoreceptor PD-1 is largely based on mouse models, but human and mouse PD-1 share only 59.6% amino acid identity. Here, we found that human PD-1 is more inhibitory than mouse PD-1, owing to stronger interactions with the ligands PD-L1 and PD-L2 and more efficient recruitment of the effector phosphatase Shp2. In a mouse melanoma model with adoptively transferred T cells, humanization of a PD-1 intracellular domain disrupted the antitumor activity of CD8<sup>+</sup> T cells and increased the magnitude of anti–PD-1 response. We identified a motif highly conserved across vertebrate PD-1 orthologs, absent in rodents, as a key determinant for differential Shp2 recruitment. Evolutionary analysis suggested that PD-1 underwent a rodent lineage–specific functional attenuation during evolution. Together, our study uncovers species-specific features of the PD-1 pathway, with implications for PD-1 evolution and differential anti–PD-(L)1 responses in mouse models and human patients.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 103","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917894","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

Extrasinusoidal macrophages are a distinct subset of immunologically active dural macrophages 窦外巨噬细胞是免疫活性硬膜巨噬细胞的一个独特亚群

IF 17.6 1区医学

Science Immunology Pub Date : 2024-12-20 DOI: 10.1126/sciimmunol.adh1129

Lukas Amann, Amelie Fell, Gianni Monaco, Roman Sankowski, Huang Zie Quann Wu, Marta Joana Costa Jordão, Katharina Borst, Maximilian Fliegauf, Takahiro Masuda, Alberto Ardura-Fabregat, Neil Paterson, Elisa Nent, James Cook, Ori Staszewski, Omar Mossad, Thorsten Falk, Antoine Louveau, Igor Smirnov, Jonathan Kipnis, Tim Lämmermann, Marco Prinz

{"title":"Extrasinusoidal macrophages are a distinct subset of immunologically active dural macrophages","authors":"Lukas Amann, Amelie Fell, Gianni Monaco, Roman Sankowski, Huang Zie Quann Wu, Marta Joana Costa Jordão, Katharina Borst, Maximilian Fliegauf, Takahiro Masuda, Alberto Ardura-Fabregat, Neil Paterson, Elisa Nent, James Cook, Ori Staszewski, Omar Mossad, Thorsten Falk, Antoine Louveau, Igor Smirnov, Jonathan Kipnis, Tim Lämmermann, Marco Prinz","doi":"10.1126/sciimmunol.adh1129","DOIUrl":"10.1126/sciimmunol.adh1129","url":null,"abstract":"<div >Although macrophages in the meningeal compartments of the central nervous system (CNS) have been comprehensively characterized under steady state, studying their contribution to physiological and pathological processes has been hindered by the lack of specific targeting tools in vivo. Recent findings have shown that the dural sinus and its adjacent lymphatic vessels act as a neuroimmune interface. However, the cellular and functional heterogeneity of extrasinusoidal dural macrophages outside this immune hub is not fully understood. Therefore, we comprehensively characterized these cells using single-cell transcriptomics, fate mapping, confocal imaging, clonal analysis, and transgenic mouse lines. Extrasinusoidal dural macrophages were distinct from leptomeningeal and CNS parenchymal macrophages in terms of their origin, expansion kinetics, and transcriptional profiles. During autoimmune neuroinflammation, extrasinusoidal dural macrophages performed efferocytosis of apoptotic granulocytes. Our results highlight a previously unappreciated myeloid cell diversity and provide insights into the brain’s innate immune system.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 102","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867118","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

NK cells restrain cytotoxic CD8+ T cells in the submandibular gland via PD-1–PD-L1 NK细胞通过PD-1-PD-L1抑制颌下腺细胞毒性CD8 + T细胞

IF 17.6 1区医学

Science Immunology Pub Date : 2024-12-20 DOI: 10.1126/sciimmunol.adl2967

Samantha M. Borys, Shanelle P. Reilly, Ian Magill, David Zemmour, Laurent Brossay

{"title":"NK cells restrain cytotoxic CD8+ T cells in the submandibular gland via PD-1–PD-L1","authors":"Samantha M. Borys, Shanelle P. Reilly, Ian Magill, David Zemmour, Laurent Brossay","doi":"10.1126/sciimmunol.adl2967","DOIUrl":"10.1126/sciimmunol.adl2967","url":null,"abstract":"<div >The increasing use of anti–programmed cell death 1 (PD-1) immune checkpoint blockade has led to the emergence of immune-related adverse events (irAEs), including dysfunction of the submandibular gland (SMG). In this study, we investigated the immunoregulatory mechanism contributing to the susceptibility of the SMG to irAEs. We found that the SMGs of PD-1–deficient mice and anti–programmed cell death ligand 1 (PD-L1)–treated mice harbor an expanded population of CD8<sup>+</sup> T cells. We demonstrate that natural killer (NK) cells expressing PD-L1 tightly regulate CD8<sup>+</sup> T cells in the SMG. When this immunoregulation is disrupted, CD8<sup>+</sup> T cells clonally expand and acquire a unique transcriptional profile consistent with T cell receptor (TCR) activation. These clonally expanded cells phenotypically overlapped with cytotoxic GzmK<sup>+</sup> CD8<sup>+</sup> T autoimmune cells identified in patients with primary Sjögren’s syndrome. Understanding how NK cells modulate CD8<sup>+</sup> T cell activity in the SMG opens new avenues for preventing irAEs in patients undergoing checkpoint blockade therapies.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 102","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867119","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

Meeting report: Hidden links in autoimmunity 会议报告：自身免疫的隐藏联系

IF 17.6 1区医学

Science Immunology Pub Date : 2024-12-20 DOI: 10.1126/sciimmunol.ads5884

Mireia Guerau-de-Arellano, Margaret A. Morris, Matthew A. Sherman, Thomas R. Esch

引用次数: 0

Erratum for the Research Article “GGNBP2 regulates MDA5 sensing triggered by self double-stranded RNA following loss of ADAR1 editing” by J. E. Heraud-Farlow et al. J. E. Heraud-Farlow等人的研究文章“GGNBP2调控ADAR1编辑缺失后自双链RNA触发的MDA5传感”的勘误。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-12-20 DOI: 10.1126/sciimmunol.adv0928

引用次数: 0

Antigen-presenting cell activation requires intrinsic and extrinsic STING signaling after the phagocytosis of DNA-damaged cells 抗原呈递细胞的激活需要dna受损细胞吞噬后的内源性和外源性STING信号

IF 17.6 1区医学

Science Immunology Pub Date : 2024-12-20 DOI: 10.1126/sciimmunol.adk7812

Seongji Park, Jeonghyun Ahn, Glen N. Barber

引用次数: 0

Crystal structure of the human LAG-3–HLA-DR1–peptide complex 人lag -3 - hla - dr1肽复合物的晶体结构

IF 17.6 1区医学

Science Immunology Pub Date : 2024-12-13 DOI: 10.1126/sciimmunol.ads5122

Jan Petersen, Carmen Llerena, Bagher Golzarroshan, Camilla Faoro, Frederic Triebel, Jamie Rossjohn

{"title":"Crystal structure of the human LAG-3–HLA-DR1–peptide complex","authors":"Jan Petersen, Carmen Llerena, Bagher Golzarroshan, Camilla Faoro, Frederic Triebel, Jamie Rossjohn","doi":"10.1126/sciimmunol.ads5122","DOIUrl":"10.1126/sciimmunol.ads5122","url":null,"abstract":"<div >T cell activity is governed by T cell receptor (TCR) signaling and constrained by immune checkpoint molecules, including programmed cell death protein 1 (PD-1), cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), and lymphocyte activation gene 3 (LAG-3). The basis for how LAG-3 binds to human leukocyte antigen class II molecules (HLA-II) remains unknown. Here, we present the 3.4-angstrom crystal structure of a LAG-3–peptide–HLA-II complex and probe the energetics of the complex interface. Coincident with the HLA-II binding site of the ancestrally related, monomeric CD4 receptor, the LAG-3 homodimer laterally engages two HLA-II molecules via distal D1 domain surfaces, imposing a 38° angular offset. The LAG-3–HLA-II interface is discontinuous and lacks involvement of the D1 extra loop, a binding site for anti–LAG-3 therapeutic monoclonal antibodies. Upon HLA-II binding, intrinsically mobile loops of the LAG-3 molecule become ordered, with contact residues highly conserved across HLA-DR, DQ, and DP allomorphs. Our data provide a structural foundation for development of immunomodulatory approaches targeting LAG-3.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 102","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815991","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

Asparagine availability controls germinal center B cell homeostasis 天冬酰胺可用性控制生发中心B细胞稳态

IF 17.6 1区医学

Science Immunology Pub Date : 2024-12-13 DOI: 10.1126/sciimmunol.adl4613

Yavuz F. Yazicioglu, Eros Marin, Hana F. Andrew, Karolina Bentkowska, Julia C. Johnstone, Robert Mitchell, Zhi Yi Wong, Kristina Zec, Joannah Fergusson, Mariana Borsa, Iwan G. A. Raza, Moustafa Attar, Mohammad Ali, Barbara Kronsteiner, Izadora L. Furlani, James I. MacRae, Michael J. Devine, Mark Coles, Christopher D. Buckley, Susanna J. Dunachie, Alexander J. Clarke

{"title":"Asparagine availability controls germinal center B cell homeostasis","authors":"Yavuz F. Yazicioglu, Eros Marin, Hana F. Andrew, Karolina Bentkowska, Julia C. Johnstone, Robert Mitchell, Zhi Yi Wong, Kristina Zec, Joannah Fergusson, Mariana Borsa, Iwan G. A. Raza, Moustafa Attar, Mohammad Ali, Barbara Kronsteiner, Izadora L. Furlani, James I. MacRae, Michael J. Devine, Mark Coles, Christopher D. Buckley, Susanna J. Dunachie, Alexander J. Clarke","doi":"10.1126/sciimmunol.adl4613","DOIUrl":"10.1126/sciimmunol.adl4613","url":null,"abstract":"<div >The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these metabolic processes are poorly understood. By integrating metabolomic and transcriptomic profiling of GC B cells, we identified that asparagine (Asn) metabolism was highly up-regulated and essential for B cell function. Asparagine synthetase (ASNS) was up-regulated after B cell activation through the integrated stress response sensor GCN2. Conditional deletion of <i>Asns</i> in B cells impaired survival and proliferation in low Asn conditions. Removal of environmental Asn by asparaginase or dietary restriction compromised the GC reaction, impairing affinity maturation and the humoral response to influenza infection. Furthermore, metabolic adaptation to the absence of Asn required ASNS, and oxidative phosphorylation, mitochondrial homeostasis, and synthesis of nucleotides were particularly sensitive to Asn deprivation. These findings demonstrate that Asn metabolism acts as a key regulator of B cell function and GC homeostasis.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 102","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815923","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

Immunopathology in human tuberculosis 人结核的免疫病理学

IF 17.6 1区医学

Science Immunology Pub Date : 2024-12-13 DOI: 10.1126/sciimmunol.ado5951

Thomas J. Scriba, Mahlatse Maseeme, Carly Young, Laura Taylor, Alasdair J. Leslie

{"title":"Immunopathology in human tuberculosis","authors":"Thomas J. Scriba, Mahlatse Maseeme, Carly Young, Laura Taylor, Alasdair J. Leslie","doi":"10.1126/sciimmunol.ado5951","DOIUrl":"10.1126/sciimmunol.ado5951","url":null,"abstract":"<div ><i>Mycobacterium tuberculosis</i> (<i>M.tb</i>) is a bacterial pathogen that has evolved in humans, and its interactions with the host are complex and best studied in humans. Myriad immune pathways are involved in infection control, granuloma formation, and progression to tuberculosis (TB) disease. Inflammatory cells, such as macrophages, neutrophils, conventional and unconventional T cells, B cells, NK cells, and innate lymphoid cells, interact via cytokines, cell-cell communication, and eicosanoid signaling to contain or eliminate infection but can alternatively mediate pathological changes required for pathogen transmission. Clinical manifestations include pulmonary and extrapulmonary TB, as well as post-TB lung disease. Risk factors for TB progression, in turn, largely relate to immune status and, apart from traditional chemotherapy, interventions primarily target immune mechanisms, highlighting the critical role of immunopathology in TB. Maintaining a balance between effector mechanisms to achieve protective immunity and avoid detrimental inflammation is central to the immunopathogenesis of TB. Many research gaps remain and deserve prioritization to improve our understanding of human TB immunopathogenesis.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 102","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815922","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 “Acquisition of suppressive function by conventional T cells limits antitumor immunity upon Treg depletion” by S. K. Whiteside et al. S. K. Whiteside等人的研究文章《常规T细胞获得抑制功能限制Treg耗竭时的抗肿瘤免疫》的勘误。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-12-13 DOI: 10.1126/sciimmunol.adu6398

引用次数: 0