IF 26.3 1区医学

Immunity Pub Date : 2025-10-21 DOI: 10.1016/j.immuni.2025.09.018

Pinar Cakmak, Jennifer H Lun, Aakanksha Singh, Jadranka Macas, Jonathan Schupp, Jonas Schuck, Zeina Mahmoud, Miriam Köhler, Tatjana Starzetz, Michael C Burger, Eike Steidl, Lucie Marie Hasse, Elke Hattingen, Karl H Plate, Yvonne Reiss, Katharina Imkeller

{"title":"Spatial immune profiling defines a subset of human gliomas with functional tertiary lymphoid structures.","authors":"Pinar Cakmak, Jennifer H Lun, Aakanksha Singh, Jadranka Macas, Jonathan Schupp, Jonas Schuck, Zeina Mahmoud, Miriam Köhler, Tatjana Starzetz, Michael C Burger, Eike Steidl, Lucie Marie Hasse, Elke Hattingen, Karl H Plate, Yvonne Reiss, Katharina Imkeller","doi":"10.1016/j.immuni.2025.09.018","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.09.018","url":null,"abstract":"<p><p>Adult-type diffuse gliomas, the most common primary brain tumors, respond poorly to immune-based therapies and are considered immunologically \"cold\" tumors. Here, we examined the features and clinical relevance of glioma intratumoral tertiary lymphoid structures (TLSs) using spatial transcriptome and proteome profiling. In a cohort of 642 gliomas, TLSs were present in 15% of tumors and associated with a remodeled perivascular space and spatial redistribution of extracellular matrix components. Three distinct TLS subtypes could be defined based on differing cellular composition and immune activity. While all subtypes lacked classical germinal center architecture, certain TLSs exhibited features of dynamic immune functions, including clonal T and B cell expansion, generation of IgA⁺ and IgG⁺ plasma cells, and dendritic cell-T cell interactions. The presence of TLSs with active immune response features correlated with improved overall survival. Thus, a functional adaptive immune response is detectable in some gliomas, with implications for stratification and treatment.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":""},"PeriodicalIF":26.3,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345140","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

ATG9A-mediated autophagy prevents inflammatory skin disease by limiting TNFR1-driven STING activation and ZBP1-dependent cell death. atg9a介导的自噬通过限制tnfr1驱动的STING激活和zbp1依赖的细胞死亡来预防炎症性皮肤病。

IF 26.3 1区医学

Immunity Pub Date : 2025-10-20 DOI: 10.1016/j.immuni.2025.09.019

Dario Priem, Jon Huyghe, Barbara Gilbert, Simon Verdonck, Tom Delanghe, Bruno Verstraeten, Esther Hoste, Peter Vandenabeele, Jonathan Maelfait, Geert van Loo, Mathieu J M Bertrand

{"title":"ATG9A-mediated autophagy prevents inflammatory skin disease by limiting TNFR1-driven STING activation and ZBP1-dependent cell death.","authors":"Dario Priem, Jon Huyghe, Barbara Gilbert, Simon Verdonck, Tom Delanghe, Bruno Verstraeten, Esther Hoste, Peter Vandenabeele, Jonathan Maelfait, Geert van Loo, Mathieu J M Bertrand","doi":"10.1016/j.immuni.2025.09.019","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.09.019","url":null,"abstract":"<p><p>Tumor necrosis factor (TNF) is a central pro-inflammatory cytokine with pathologic roles in chronic inflammatory and autoimmune disorders. The mechanisms by which TNF sensing drives the pathogenesis of these diseases are not fully understood. We previously showed that the lack of the autophagic lipid scramblase ATG9A in mouse keratinocytes leads to severe dermatitis and systemic inflammation, with features resembling human skin disorders. We now demonstrate that the disease is initiated by TNF but caused by cGAS/STING-dependent type I interferon (IFN) production and subsequent ZBP1-dependent apoptosis and necroptosis. ATG9A prevented the pathogenesis of the disease by engaging both light-chain 3 (LC3)-dependent and -independent autophagy. These results uncover an additional pathological arm of TNF signaling, opening avenues for alternative therapeutic interventions for TNF-driven diseases. Moreover, this study reveals another pathophysiological function of LC3-independent autophagy in restraining type I IFN production, which triggers the development or exacerbation of an interferonopathy in mice and humans.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":""},"PeriodicalIF":26.3,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345081","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

Cutting the Gordian knot: Untangling gasdermin C from pyroptosis 切断戈甸结：从焦亡中解开缠结的气皮素C

IF 32.4 1区医学

Immunity Pub Date : 2025-10-14 DOI: 10.1016/j.immuni.2025.09.015

Zhaoyu Lin, Hai-Bin Ruan

引用次数: 0

Resident memory T cells call the shots in tissue immunity 常驻记忆T细胞在组织免疫中发号施令

IF 32.4 1区医学

Immunity Pub Date : 2025-10-14 DOI: 10.1016/j.immuni.2025.09.017

Sigrun Stulz, Georg Gasteiger

引用次数: 0

Alzheimer’s alphabet soup: Find the letters “Z-DNA-ZBP1-RIPK1” 阿尔茨海默氏症字母汤：找到字母“Z-DNA-ZBP1-RIPK1”

IF 32.4 1区医学

Immunity Pub Date : 2025-10-14 DOI: 10.1016/j.immuni.2025.09.010

Jake A. Gertie, Hachung Chung

引用次数: 0

Nurture over nature in fate decisions of antigen-specific CD8+ T cell clones from an endogenous repertoire 后天培养在内源性抗原特异性CD8+ T细胞克隆的命运决定中的作用

IF 32.4 1区医学

Immunity Pub Date : 2025-10-14 DOI: 10.1016/j.immuni.2025.09.005

Adrian Straub, Zahra Abedi, Dirk H. Busch, Veit R. Buchholz

{"title":"Nurture over nature in fate decisions of antigen-specific CD8+ T cell clones from an endogenous repertoire","authors":"Adrian Straub, Zahra Abedi, Dirk H. Busch, Veit R. Buchholz","doi":"10.1016/j.immuni.2025.09.005","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.09.005","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>Abdullah et al.<sup>1</sup> recently set out to gauge the influence of T cell receptor (TCR)-intrinsic vs. -extrinsic factors on memory vs. effector fate decisions of CD8<sup>+</sup> T cells. They concluded that “a majority of TCR clonotypes were highly biased toward memory or effector fate,” and that “TCR intrinsic biases […] were dominant over environmental cues.” We argue that these conclusions cannot be drawn based on the authors’ limited clonotypic data and are strongly opposed by our own observation of highly</section></section><section><section><h2>Acknowledgments</h2>The ultra-deep H2-K<sup>b</sup>/SIINFEKL-specific TCR library was created as part of the MATCHMAKERS team, supported by the Cancer Grand Challenges partnership financed by <span>CRUK</span> (CGCATF-2023/100002) and the <span>National Cancer Institute</span> (1OT2CA297204-01). A.S., Z.A., and D.H.B. are members of the MATCHMAKERS team. The work was further funded by SFB-TRR 338/1 2021- 452881907 (project A01 [D.H.B.] and project B02 [V.R.B.]) and the <span>European Research Council</span> (starting grant 949719 SCIMAP to V.R.B.).</section></section><section><section><h2>Declaration of interests</h2>The authors declare no competing interests.</section></section>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"81 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283462","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

Primate resident memory T cells activate humoral and stromal immunity 灵长类动物常驻记忆T细胞激活体液和基质免疫

IF 32.4 1区医学

Immunity Pub Date : 2025-10-14 DOI: 10.1016/j.immuni.2025.09.009

Vineet Joag, Benjamin N. Bimber, Clare F. Quarnstrom, Venkata S. Bollimpelli, Jason M. Schenkel, Kathryn A. Fraser, Mario Bertogliat, Andrew G. Soerens, J. Michael Stolley, Stephen D. O’Flanagan, Pamela C. Rosato, Noah V. Gavil, Marco Künzli, Jason S. Mitchell, Traci Legere, Sherrie Jean, Amit A. Upadhyay, C. Yong Kang, James Gibbs, Jonathan W. Yewdell, David Masopust

{"title":"Primate resident memory T cells activate humoral and stromal immunity","authors":"Vineet Joag, Benjamin N. Bimber, Clare F. Quarnstrom, Venkata S. Bollimpelli, Jason M. Schenkel, Kathryn A. Fraser, Mario Bertogliat, Andrew G. Soerens, J. Michael Stolley, Stephen D. O’Flanagan, Pamela C. Rosato, Noah V. Gavil, Marco Künzli, Jason S. Mitchell, Traci Legere, Sherrie Jean, Amit A. Upadhyay, C. Yong Kang, James Gibbs, Jonathan W. Yewdell, David Masopust","doi":"10.1016/j.immuni.2025.09.009","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.09.009","url":null,"abstract":"CD8<sup>+</sup> resident memory T (Trm) cells comprise a small population of frontline sentinels compared with the large tissues they surveil, making outsized contributions to immune protection from infection. Here, we interrogated mechanisms of Trm cell function in primates. Intravenous immunization of macaques with a simian immunodeficiency virus (SIV)-gag-containing heterologous prime-boost-boost vaccine established memory T cells in >30 tissues, including visceral and mucosal compartments. Upon <em>in vivo</em> reactivation in the reproductive tract, antigen-sensing CD8<sup>+</sup> Trm activated local stromal, parenchymal, and innate and adaptive immune cells. Stromal and parenchymal cells accentuated leukocyte migration and antiviral defenses. B and plasma cells mobilized into the vaginal mucosa, and bloodborne CD4<sup>+</sup> T cells were recruited and adopted a host-defense program. Our findings demonstrate that systemic vaccination promotes a Trm cell response in barrier compartments and that Trm cells repurpose abundant neighboring stromal, parenchymal, and immune cells to amplify alarm signals and activate diverse host defenses.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"120 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283789","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

Reply to nurture over nature in fate decisions of antigen-specific CD8+ T cell clones from an endogenous repertoire 在内源性抗原特异性CD8+ T细胞克隆的命运决定中，对培养的应答高于自然

IF 32.4 1区医学

Immunity Pub Date : 2025-10-14 DOI: 10.1016/j.immuni.2025.09.006

Leena Abdullah, Joshua J. Obar, Yina H. Huang

{"title":"Reply to nurture over nature in fate decisions of antigen-specific CD8+ T cell clones from an endogenous repertoire","authors":"Leena Abdullah, Joshua J. Obar, Yina H. Huang","doi":"10.1016/j.immuni.2025.09.006","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.09.006","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>Upon activation, individual CD8<sup>+</sup> clones decide between effector and memory T cell fates by integrating intrinsic T cell receptor (TCR) signals or “nature” and extrinsic signals from co-stimulatory ligands and inflammatory cytokines or “nurture”. The collective antigen-specific CD8<sup>+</sup> T cell response is composed of differential fate decisions made by ∼100–1,000 individual clones. Several models describe how variations in nature drive effector vs. memory T cell differentiation, including the</section></section><section><section><h2>Acknowledgments</h2>This work was supported in part by the <span>National Institutes of Health</span> (NIH) grant R01-AI131975 to Y.H.H.; Tom and Susan Stepp to Y.H.H.; <span>Prouty Developmental grant</span> to Y.H.H.; <span>NIH</span> grants P20-GM130454, S10-OD025235, and S10-OD030242, which support the single-cell genomics core; and <span>NIH</span> grant P30-CA023108, which supports the <span>Dartmouth Cancer Center’s flow cytometry</span> (RRID: <span>SCR_019165</span>) and genomics (RRID: <span>SCR_021293</span>) shared resources.</section></section><section><section><h2>Author contributions</h2>L.A. and Y.H.H. wrote the original manuscript. J.J.O. provided feedback on the final manuscript.</section></section><section><section><h2>Declaration of interests</h2>The authors declare no competing interests.</section></section>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"3 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283466","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

Burning the candle at both ends: ROS-mediated telomere damage drives T cell dysfunction 点燃蜡烛两端：ros介导的端粒损伤驱动T细胞功能障碍

IF 32.4 1区医学

Immunity Pub Date : 2025-10-14 DOI: 10.1016/j.immuni.2025.09.016

Alexander J. Wesolowski, Rahul Roychoudhuri

引用次数: 0

Fibroblasts are not so scar-y in brain injury 成纤维细胞在脑损伤中并不那么可怕

IF 32.4 1区医学

Immunity Pub Date : 2025-10-14 DOI: 10.1016/j.immuni.2025.09.013

Danae N. Mitchell, Julie A. Siegenthaler

引用次数: 0

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