Science Immunology最新文献_第10页

Erratum for the Research Article “A noncanonical cytoplasmic role for BUB1 in restraining DNA damage–induced dsRNA accumulation and sensing within stress granules” 研究文章“BUB1在抑制DNA损伤诱导的dsRNA积累和感知中的非规范细胞质作用”的勘误

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-10 DOI: 10.1126/sciimmunol.aeh4448

引用次数: 0

The rise of spatial TCR profiling: Emerging technologies and open challenges 空间TCR分析的兴起：新兴技术和开放挑战

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-10 DOI: 10.1126/sciimmunol.aeg7517

Yinglu Tang, Tao Wang

引用次数: 0

The epitope tax: Antibody feedback and the economics of germinal center competition 表位税：抗体反馈与生发中心竞争的经济学

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-03 DOI: 10.1126/sciimmunol.aeh4815

Wallace P. Bezerra, Adam Williams

引用次数: 0

Claudins interact with LILRB immune inhibitory receptors to promote myeloid immunosuppression in cancer claudin与LILRB免疫抑制受体相互作用，促进肿瘤中髓系免疫抑制

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-03 DOI: 10.1126/sciimmunol.adt7832

Xiaoye Liu, Ryan Huang, Zhiqiang Ku, Jingjing Xie, Heyu Chen, Yubo He, Qi Lou, Chengcheng Zhang, Xing Yang, Cheryl Lewis, Jade Homsi, Ankit Gupta, Lei Dong, Kenian Chen, Annabel Tu, Liming Du, Hailong Yu, Qing Hu, Meng Fang, Bufan Li, A. E. M. Adan Khan, Caroline Simith, Samuel John, Lin Xu, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

{"title":"Claudins interact with LILRB immune inhibitory receptors to promote myeloid immunosuppression in cancer","authors":"Xiaoye Liu, Ryan Huang, Zhiqiang Ku, Jingjing Xie, Heyu Chen, Yubo He, Qi Lou, Chengcheng Zhang, Xing Yang, Cheryl Lewis, Jade Homsi, Ankit Gupta, Lei Dong, Kenian Chen, Annabel Tu, Liming Du, Hailong Yu, Qing Hu, Meng Fang, Bufan Li, A. E. M. Adan Khan, Caroline Simith, Samuel John, Lin Xu, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang","doi":"10.1126/sciimmunol.adt7832","DOIUrl":"10.1126/sciimmunol.adt7832","url":null,"abstract":"<div >The mechanisms underlying tumor cell–myeloid cell interactions in the tumor microenvironment (TME) remain unclear, and predictive biomarkers for patient response to myeloid checkpoint blockade are lacking. This study identified specific binding between tight junction claudins (CLDNs) and leukocyte immunoglobulin-like receptor subfamily B2 (LILRB2) and LILRB5. In multiple human cancer cohorts, the spatial proximity of LILRB2-positive macrophages to CLDN-expressing cancer cells correlated with clinical outcomes, highlighting this spatial relationship as a potential biomarker. In syngeneic LILRB2-transgenic and humanized mouse models, CLDN18.2-LILRB2 interactions triggered bidirectional signaling, enhanced the immunosuppressive activity of myeloid cells, and accelerated tumor progression. These effects were reversed by LILRB2 blockade. The CLDN-LILRB2 axis sustained immunosuppression by regulating NF-κB and STAT signaling pathways. Our findings reveal a mechanism of myeloid cell regulation by tight junction proteins in the TME, offering a rationale for targeting this pathway in cancer therapy.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 118","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599610","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

Upstream ORFs control TNFR1 abundance and tissue tolerance to TNF 上游orf控制TNFR1丰度和组织对TNF的耐受性

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-03 DOI: 10.1126/sciimmunol.aeb6484

Biao Ma, Wenxin Lyu, John Rizk, Xiaoyue Han, Majken Kjær, Vinnycius Pereira Almeida, Malin Jessen, Max Benjamin Sauerland, Carol Sze Ki Leung, Benoit J. Van den Eynde, Xin Lu, Mads Gyrd-Hansen

{"title":"Upstream ORFs control TNFR1 abundance and tissue tolerance to TNF","authors":"Biao Ma, Wenxin Lyu, John Rizk, Xiaoyue Han, Majken Kjær, Vinnycius Pereira Almeida, Malin Jessen, Max Benjamin Sauerland, Carol Sze Ki Leung, Benoit J. Van den Eynde, Xin Lu, Mads Gyrd-Hansen","doi":"10.1126/sciimmunol.aeb6484","DOIUrl":"10.1126/sciimmunol.aeb6484","url":null,"abstract":"<div >Tumor necrosis factor (TNF) orchestrates immune responses but can also drive inflammation-associated tissue damage. However, the mechanisms governing tissue tolerance to TNF remain poorly understood. Here, we reveal that TNF receptor 1 (TNFR1) abundance is regulated by two upstream open reading frames (uORFs) in the 5′ untranslated region of <i>TNFRSF1A</i> and demonstrate that this is a key determinant of TNF tolerance. uORF2 dominantly limits TNFR1 translation, and its disruption increases TNFR1 levels, leading to excessive TNF-induced gene activation and cell death in cell culture. By contrast, uORF1 dynamically regulates TNFR1 levels in response to inflammatory and stress signals. In mice, uORF2 protects against TNF-driven systemic inflammatory response syndrome and liver pathology. We additionally report that the translation of other immune receptor messenger RNAs, including <i>TLR4</i>, <i>IFNAR1</i>, and <i>IFNGR2</i>, is also controlled by uORFs. Thus, regulation of TNFR1 levels and possibly of other immune receptors emerges as a mechanism safeguarding against excessive immune responses and tissue damage.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 118","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599611","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

Copper supports regulatory T cell energetic state to sustain peripheral immune tolerance 铜支持调节性T细胞的能量状态以维持外周免疫耐受

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-03 DOI: 10.1126/sciimmunol.aec2573

Yage Zhang, Fan Shi, Haoyu Tang, Tianyi Wang, Hui Zhao, Jie Chang, Chengyao Zhu, Wei Xu, Zhenli Zhu, Jing-wen Lin, Yanfang Wang, Xiangguang Shi, Jiucun Wang, Junxia Min, Fudi Wang, Qian Wu, Songmin Ying

{"title":"Copper supports regulatory T cell energetic state to sustain peripheral immune tolerance","authors":"Yage Zhang, Fan Shi, Haoyu Tang, Tianyi Wang, Hui Zhao, Jie Chang, Chengyao Zhu, Wei Xu, Zhenli Zhu, Jing-wen Lin, Yanfang Wang, Xiangguang Shi, Jiucun Wang, Junxia Min, Fudi Wang, Qian Wu, Songmin Ying","doi":"10.1126/sciimmunol.aec2573","DOIUrl":"10.1126/sciimmunol.aec2573","url":null,"abstract":"<div >Fine-tuning of energy metabolism is essential for the survival and suppressive function of regulatory T cells (T<sub>reg</sub> cells). Here, we show that T<sub>reg</sub> cells with a high energetic state display enhanced functional capacity. Using a screen of mitochondrial inhibitors, we identified copper chelators and ionophores as modulators of T<sub>reg</sub> cell energetic state. T cell receptor (TCR) stimulation in vitro and human autoimmune conditions increased the labile copper pool in T<sub>reg</sub> cells. In murine T<sub>reg</sub> cells, we characterized Slc31a1 as a major copper transporter that supports oxidative phosphorylation, sustains nicotinamide adenine dinucleotide/reduced NAD<sup>+</sup> (NAD<sup>+</sup>/NADH) homeostasis, and promotes histone acetylation at loci encoding core T<sub>reg</sub> cell functional molecules. These mechanisms collectively ensured energy production and T<sub>reg</sub> cell functionality, which were indispensable for peripheral immune tolerance but could be rescued by the copper ionophore elesclomol. Together, our findings identify copper metabolism as a critical regulator of T<sub>reg</sub> cell functionality and suggest potential therapeutic avenues for autoimmune diseases.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 118","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599628","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

Skull-pting meningeal immunity: Skull bone channels shape neonatal meningeal immune cell trafficking 颅骨-脑膜免疫：颅骨通道塑造新生儿脑膜免疫细胞的运输

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-03 DOI: 10.1126/sciimmunol.aeh4811

Emma N. Barnes, David R. Martinez

引用次数: 0

Intestinal epithelial MHC class II induces encephalitogenic CD4 T cells and initiates central nervous system autoimmunity 肠上皮MHC II类诱导脑源性CD4 T细胞并启动中枢神经系统自身免疫

IF 16.3 1区医学

Science Immunology Pub Date : 2026-03-27 DOI: 10.1126/sciimmunol.aec1627

Shohei Suzuki, Kentaro Miyamoto, Anna Tojo, Yusuke Yoshimatsu, Toshiaki Teratani, Hitoshi Uchida, Yasuhiro Nemoto, Ryuichi Okamoto, Andreas Michael Sihombing, Toshiro Sato, Jin Nakahara, Takanori Kanai, Tomohisa Sujino

{"title":"Intestinal epithelial MHC class II induces encephalitogenic CD4 T cells and initiates central nervous system autoimmunity","authors":"Shohei Suzuki, Kentaro Miyamoto, Anna Tojo, Yusuke Yoshimatsu, Toshiaki Teratani, Hitoshi Uchida, Yasuhiro Nemoto, Ryuichi Okamoto, Andreas Michael Sihombing, Toshiro Sato, Jin Nakahara, Takanori Kanai, Tomohisa Sujino","doi":"10.1126/sciimmunol.aec1627","DOIUrl":"10.1126/sciimmunol.aec1627","url":null,"abstract":"<div >The intestinal epithelium plays a critical role in immune-microbiota interactions, yet its contribution to systemic autoimmunity remains unclear. Here, we identify intestinal epithelial cells (IECs) as initiators of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). In both EAE mice and patients with MS, IECs up-regulate antigen presentation pathways and are associated with increased intestinal T helper 17 (T<sub>H</sub>17) cell accumulation. Epithelial major histocompatibility complex class II (MHC II) was highly expressed during EAE, particularly in the ileum, and its conditional deletion reduced pathogenic T<sub>H</sub>17 cell generation and disease severity. Using parabiosis and photoconversion models, we demonstrate that T<sub>H</sub>17 cells induced in the intestinal lamina propria migrate to the spinal cord. Functional coculture assays showed that IEC organoids with cognate myelin oligodendrocyte glycoprotein antigen induce RORγt<sup>+</sup>CD4<sup>+</sup> T cell differentiation in an MHC II–dependent manner. These findings uncover a conserved gut–central nervous system axis in autoimmunity and position epithelial antigen presentation as a key initiator of neuroinflammation.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 117","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147523906","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

Palmitate-induced mitochondrial damage restricts histone acetylation in CD8 T cells to impair antitumor immunity 棕榈酸诱导的线粒体损伤限制CD8 T细胞组蛋白乙酰化，从而损害抗肿瘤免疫

IF 16.3 1区医学

Science Immunology Pub Date : 2026-03-27 DOI: 10.1126/sciimmunol.aeb1459

Silvia Tiberti, Sara Gennari, Martina Romeo, Ilir Sheraj, Mohamed Faisal Kassir, Juan Fernández-García, Carina B. Nava Lauson, Roberta Noberini, Carlotta Catozzi, Tiziano Dallavilla, Mattia Ballerini, Alessia Loffreda, Simona G. Codreanu, Stacy D. Sherrod, Katrina L. Leaptrot, Alexandra C. Schrimpe-Rutledge, John A. McLean, Martin H. Schaefer, Simona Rodighiero, Tiziana Bonaldi, Sarah-Maria Fendt, Besim Ogretmen, Sara Sdelci, Luigi Nezi, Teresa Manzo

{"title":"Palmitate-induced mitochondrial damage restricts histone acetylation in CD8 T cells to impair antitumor immunity","authors":"Silvia Tiberti, Sara Gennari, Martina Romeo, Ilir Sheraj, Mohamed Faisal Kassir, Juan Fernández-García, Carina B. Nava Lauson, Roberta Noberini, Carlotta Catozzi, Tiziano Dallavilla, Mattia Ballerini, Alessia Loffreda, Simona G. Codreanu, Stacy D. Sherrod, Katrina L. Leaptrot, Alexandra C. Schrimpe-Rutledge, John A. McLean, Martin H. Schaefer, Simona Rodighiero, Tiziana Bonaldi, Sarah-Maria Fendt, Besim Ogretmen, Sara Sdelci, Luigi Nezi, Teresa Manzo","doi":"10.1126/sciimmunol.aeb1459","DOIUrl":"10.1126/sciimmunol.aeb1459","url":null,"abstract":"<div >Lipid accumulation in the tumor microenvironment is a hallmark of solid tumors, with increased palmitate (PA) availability fostering tumor progression. Although PA’s direct effects on cancer cells are well described, its impact on CD8 T cells [cytotoxic T lymphocytes (CTLs)] remains unclear. Here, we show that PA irreversibly impairs CTL mitochondrial metabolism, leading to the loss of effector functions and compromised antitumor immunity. PA-induced mitochondrial dysfunction reduced histone acetylation and chromatin accessibility, suppressing transcription of genes involved in T cell replication and effector programs. We identified sphingosine kinase 2 (SPHK2) as a key mediator of PA-induced dysfunction, with pharmacological inhibition of SPHK2 restoring mitochondrial fitness, rescuing CTL effector function, and promoting antitumor activity. These findings uncover a distinct mechanism by which PA drives immune evasion in tumors and highlight SPHK2 as a potential therapeutic target to enhance T cell–based immunotherapies.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 117","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147523904","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 "TCRγ constant usage tunes human γδ T cell antigen sensitivity, thymic programming, and peripheral function". 研究文章“TCRγ恒定使用调节人γδ T细胞抗原敏感性，胸腺编程和外周功能”的勘误。

IF 24.8 1区医学

Science Immunology Pub Date : 2026-03-20 DOI: 10.1126/sciimmunol.aeg7865

引用次数: 0