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An interleukin-9-ZBTB18 axis promotes germinal center development of memory B cells
IF 32.4 1区 医学
Immunity Pub Date : 2025-03-18 DOI: 10.1016/j.immuni.2025.02.021
Xiaocui Luo, Xiaoxiao Hou, Yifeng Wang, Ye Li, Shangcheng Yu, Hai Qi
{"title":"An interleukin-9-ZBTB18 axis promotes germinal center development of memory B cells","authors":"Xiaocui Luo, Xiaoxiao Hou, Yifeng Wang, Ye Li, Shangcheng Yu, Hai Qi","doi":"10.1016/j.immuni.2025.02.021","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.021","url":null,"abstract":"Memory B cell (MBC) development from germinal centers (GCs) entails profound changes in cell cycling, localization, and survival. Here, we examined the mechanisms that induce the memory program, focusing on interleukin (IL)-9, given its importance for normal recall antibody responses. Using adoptive transfer and radiation chimera models, we found that T cell-derived IL-9 was required for MBC development and function. By contrast, B cells deficient in IL-9 generated functionally normal MBCs that support antibody recall normally. IL-9 induced expression of the transcriptional repressor ZBTB18 in GC memory precursor cells and MBCs. ZBTB18 was dispensable for naive B cell activation and GC formation but required for the development of GC-derived MBCs. ZBTB18 directly repressed the expression of a suite of genes encoding cyclin and cyclin-dependent kinases, pro-apoptotic genes <em>Bid</em> and <em>Casp3</em>, and the GC-retaining factor <em>S1pr2</em>. Lack of IL-9-mediated instruction or intrinsic programming by ZBTB18 impaired GC-derived MBC development and antibody recall. Thus, an IL-9-ZBTB18 axis instructs the development of functional B cell memory from GCs.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"14 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640501","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
Single-cell atlas of endothelial and mural cells across primary and metastatic brain tumors
IF 32.4 1区 医学
Immunity Pub Date : 2025-03-18 DOI: 10.1016/j.immuni.2025.02.022
Leire Bejarano, Joao Lourenco, Annamaria Kauzlaric, Eleni Lamprou, Catia F. Costa, Sabine Galland, Roeltje R. Maas, Paola Guerrero Aruffo, Nadine Fournier, Jean-Philippe Brouland, Andreas F. Hottinger, Roy T. Daniel, Monika E. Hegi, Johanna A. Joyce
{"title":"Single-cell atlas of endothelial and mural cells across primary and metastatic brain tumors","authors":"Leire Bejarano, Joao Lourenco, Annamaria Kauzlaric, Eleni Lamprou, Catia F. Costa, Sabine Galland, Roeltje R. Maas, Paola Guerrero Aruffo, Nadine Fournier, Jean-Philippe Brouland, Andreas F. Hottinger, Roy T. Daniel, Monika E. Hegi, Johanna A. Joyce","doi":"10.1016/j.immuni.2025.02.022","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.022","url":null,"abstract":"Central nervous system (CNS) malignancies include primary tumors, such as gliomas, and brain metastases (BrMs) originating from diverse extracranial cancers. The blood-brain barrier (BBB) is a key structural component of both primary and metastatic brain cancers. Here, we comprehensively analyzed the two major BBB cell types, endothelial and mural cells, across non-tumor brain tissue, isocitrate dehydrogenase (<em>IDH</em>) mutant (<em>IDH</em> mut) low-grade gliomas, <em>IDH</em> wild-type (<em>IDH</em> WT) high-grade glioblastomas (GBMs), and BrMs from various primary tumors. Bulk and single-cell RNA sequencing, integrated with spatial analyses, revealed that GBMs, but not low-grade gliomas, exhibit significant alterations in the tumor vasculature, including the emergence of diverse pathological vascular cell subtypes. However, these alterations are less pronounced in GBMs than in BrMs. Notably, the BrM vasculature shows higher permeability and more extensive interactions with distinct immune cell populations. This vascular atlas presents a resource toward understanding of tumor-specific vascular features in the brain, providing a foundation for developing vascular- and immune-targeting therapies.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"61 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640500","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
Anti-vascular endothelial growth factor treatment potentiates immune checkpoint blockade through a BAFF- and IL-12-dependent reprogramming of the TME
IF 32.4 1区 医学
Immunity Pub Date : 2025-03-14 DOI: 10.1016/j.immuni.2025.02.017
Mohamed-Reda Benmebarek, Cihan Oguz, Matthias Seifert, Benjamin Ruf, Yuta Myojin, Kylynda C. Bauer, Patrick Huang, Chi Ma, Marina Villamor-Payà, Francisco Rodriguez-Matos, Marlaine Soliman, Rajiv Trehan, Cecilia Monge, Changqing Xie, David E. Kleiner, Bradford J. Wood, Elliot B. Levy, Anuradha Budhu, Noemi Kedei, Christian T. Mayer, Tim F. Greten
{"title":"Anti-vascular endothelial growth factor treatment potentiates immune checkpoint blockade through a BAFF- and IL-12-dependent reprogramming of the TME","authors":"Mohamed-Reda Benmebarek, Cihan Oguz, Matthias Seifert, Benjamin Ruf, Yuta Myojin, Kylynda C. Bauer, Patrick Huang, Chi Ma, Marina Villamor-Payà, Francisco Rodriguez-Matos, Marlaine Soliman, Rajiv Trehan, Cecilia Monge, Changqing Xie, David E. Kleiner, Bradford J. Wood, Elliot B. Levy, Anuradha Budhu, Noemi Kedei, Christian T. Mayer, Tim F. Greten","doi":"10.1016/j.immuni.2025.02.017","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.017","url":null,"abstract":"Anti-vascular endothelial growth factor (VEGF) treatment has shown clinical activity together with immune checkpoint blockade (ICB), but the exact mechanism is not known. We show that VEGF blockade in combination with anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) + anti-programmed death-ligand 1 (PD-L1) in cholangiocarcinoma (CCA) potentiated a multimodal mechanism dependent on B cell activating factor (BAFF), leading to a proinflammatory B cell response. It led to a BAFF- and interleukin (IL)-12-dependent expansion and rewiring of T regulatory cells (Tregs) toward an anti-tumor T helper-1 (Th-1)-like fragile state. We translated this approach to the clinic and observed immunological changes characterized by Treg cell expansion and rewiring toward fragile and unstable states. We explored the effect of VEGF receptor 2 (VEGFR2) signaling on Treg cell transcriptional programming and established a mouse model ablating VEGFR2 expression on Treg cells. This study reveals the immunological interplay resulting from targeting VEGF together with CTLA-4 and PD-L1 blockade.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"23 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618561","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 resident memory cells arise from NK cells that accumulate in tissues independently of persistent local infection
IF 32.4 1区 医学
Immunity Pub Date : 2025-03-11 DOI: 10.1016/j.immuni.2025.02.019
Iona S. Schuster, Matthew E. Wikstrom, Christopher E. Andoniou, Mariapia A. Degli-Esposti
{"title":"NK resident memory cells arise from NK cells that accumulate in tissues independently of persistent local infection","authors":"Iona S. Schuster, Matthew E. Wikstrom, Christopher E. Andoniou, Mariapia A. Degli-Esposti","doi":"10.1016/j.immuni.2025.02.019","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.019","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>A recent study by Gasteiger and colleagues<sup>1</sup> described a population of circulating natural killer (NK) cells that are recruited and retained in the skin for several weeks following local viral (vaccinia virus) and bacterial (Staphylococcus aureus) infections. These cells, which the authors refer to as tissue resident (tr)NK cells, exhibit increased production of effector molecules (interferon [IFN]-γ, granzyme B [Gzmb], perforin [Prf1]) upon re-challenge, suggesting a role in enhanced pathogen</section></section><section><section><h2>Acknowledgments</h2>The work was supported by funding from the <span>National Health and Medical Research Council of Australia</span> (NHMRC <span>2004397</span>, <span>1119298</span>, and <span>2026377</span>).</section></section><section><section><h2>Declaration of interests</h2>The authors declare no competing interests.</section></section>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"20 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589990","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
Lactate: A key regulator of the immune response
IF 32.4 1区 医学
Immunity Pub Date : 2025-03-11 DOI: 10.1016/j.immuni.2025.02.008
Alba Llibre, Salih Kucuk, Atrayee Gope, Michelangelo Certo, Claudio Mauro
{"title":"Lactate: A key regulator of the immune response","authors":"Alba Llibre, Salih Kucuk, Atrayee Gope, Michelangelo Certo, Claudio Mauro","doi":"10.1016/j.immuni.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.008","url":null,"abstract":"Lactate, the end product of both anaerobic and aerobic glycolysis in proliferating and growing cells—with the latter process known as the Warburg effect—is historically considered a mere waste product of cell and tissue metabolism. However, research over the past ten years has unveiled multifaceted functions of lactate that critically shape and impact cellular biology. Beyond serving as a fuel source, lactate is now known to influence gene expression through histone modification and to function as a signaling molecule that impacts a wide range of cellular activities. These properties have been particularly studied in the context of both adaptive and innate immune responses. Here, we review the diverse roles of lactate in the regulation of the immune system during homeostasis and disease pathogenesis (including cancer, infection, cardiovascular diseases, and autoimmunity). Furthermore, we describe recently proposed therapeutic interventions for manipulating lactate metabolism in human diseases.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"68 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143590044","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
Parts and ICRAFTs: Finding new immunotherapy targets
IF 32.4 1区 医学
Immunity Pub Date : 2025-03-11 DOI: 10.1016/j.immuni.2025.02.016
Kevin Bi, Kathleen B. Yates
{"title":"Parts and ICRAFTs: Finding new immunotherapy targets","authors":"Kevin Bi, Kathleen B. Yates","doi":"10.1016/j.immuni.2025.02.016","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.016","url":null,"abstract":"CRISPR screens are widely utilized to identify genes that regulate immune function or mediate sensitivity of cancer cells to immune attack. In this issue of <em>Immunity</em>, Zeng et al. present a computational framework for uncovering gene targets with dual function in both cancer and immune cells and nominate <em>TNFAIP3</em> as a synergistic target whose ablation strongly elicits an antitumor response.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"87 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589993","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
Differentiation of tissue-resident NK cells: Why origin and context matter
IF 32.4 1区 医学
Immunity Pub Date : 2025-03-11 DOI: 10.1016/j.immuni.2025.02.020
Christin Friedrich, Tommaso Torcellan, Georg Gasteiger
{"title":"Differentiation of tissue-resident NK cells: Why origin and context matter","authors":"Christin Friedrich, Tommaso Torcellan, Georg Gasteiger","doi":"10.1016/j.immuni.2025.02.020","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.020","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>In their letter to <em>Immunity</em>, Degli-Esposti and colleagues<sup>1</sup> discuss the potential origins of tissue-resident natural killer (trNK) cells and the inflammatory contexts enabling their differentiation. These largely unresolved issues are relevant for NK-based cellular therapies and our understanding of tissue immunity. Here, we examine key complementarities and differences between their work and our recent work,<sup>2</sup> highlighting future challenges and open research questions.TrNK cells are found in a</section></section><section><section><h2>Declaration of interests</h2>The authors declare no competing interests.</section></section>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"10 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589991","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
SPeak to the heart
IF 32.4 1区 医学
Immunity Pub Date : 2025-03-11 DOI: 10.1016/j.immuni.2025.02.014
Min Zhang, Zhen Zhang
{"title":"SPeak to the heart","authors":"Min Zhang, Zhen Zhang","doi":"10.1016/j.immuni.2025.02.014","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.014","url":null,"abstract":"Neuroimmune regulation modulates responses to cardiovascular stress and injury. In this issue of <em>Immunity</em>, Perrotta et al. delineate a heart-brain-spleen axis that induces adaptive cardiac remodeling in response to pressure overload, highlighting a SPeak mechanism (spleen-derived PlGF efflux activates cardiac macrophages).","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"31 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143590201","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 CREscendoing promise of HDAC targeting to limit atherosclerosis
IF 32.4 1区 医学
Immunity Pub Date : 2025-03-11 DOI: 10.1016/j.immuni.2025.02.010
Máté G. Kiss, Christoph J. Binder
{"title":"The CREscendoing promise of HDAC targeting to limit atherosclerosis","authors":"Máté G. Kiss, Christoph J. Binder","doi":"10.1016/j.immuni.2025.02.010","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.010","url":null,"abstract":"The factors that modulate the inflammatory response in atherosclerosis are not well defined. In this issue of <em>Immunity</em>, Asare et al. examine the impact of a <em>cis</em>-regulatory element (CRE) that controls expression of <em>HDAC9</em> and find that HDAC9-mediated deacetylation of NLRP3 might be the mechanism by which genetic variants in this conserved CRE influence the inflammation associated with human atherosclerosis.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"29 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589988","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
Immo-bile-izing CD8+ T cell anti-tumor immunity
IF 32.4 1区 医学
Immunity Pub Date : 2025-03-11 DOI: 10.1016/j.immuni.2025.02.015
Scott A. Read, Golo Ahlenstiel
{"title":"Immo-bile-izing CD8+ T cell anti-tumor immunity","authors":"Scott A. Read, Golo Ahlenstiel","doi":"10.1016/j.immuni.2025.02.015","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.015","url":null,"abstract":"Hepatocellular carcinoma is poorly responsive to immune checkpoint blockade. In a recent issue of <em>Science</em>, Varanasi et al. reveal how bile acids dampen anti-tumor CD8<sup>+</sup> T cell responses in the liver, contributing to cancer progression and poor immunotherapy outcomes.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"29 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143590051","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
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