Nature Immunology最新文献_第10页

Aberrant protein translation promotes T cell exhaustion 异常的蛋白质翻译促进T细胞衰竭

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-07-25 DOI: 10.1038/s41590-025-02244-1

引用次数: 0

Genetic variation in the activity of a TREM2–p53 signaling axis determines oxygen-induced lung injury TREM2-p53信号轴活性的遗传变异决定了氧诱导的肺损伤

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-07-25 DOI: 10.1038/s41590-025-02217-4

Yohei Abe, Nathanael J. Spann, Wenxi Tang, Fenghua Zeng, Cadence Seymour, Sean Jansky, Jason L. Guo, Robert Huff, Kelly Chanthavixay, John Lalith Charles Richard, Miguel Mooney, Debanjan Dhar, Souradipta Ganguly, David M. Lopez, Michael T. Longaker, Christopher Benner, Christopher K. Glass, Eniko Sajti

{"title":"Genetic variation in the activity of a TREM2–p53 signaling axis determines oxygen-induced lung injury","authors":"Yohei Abe, Nathanael J. Spann, Wenxi Tang, Fenghua Zeng, Cadence Seymour, Sean Jansky, Jason L. Guo, Robert Huff, Kelly Chanthavixay, John Lalith Charles Richard, Miguel Mooney, Debanjan Dhar, Souradipta Ganguly, David M. Lopez, Michael T. Longaker, Christopher Benner, Christopher K. Glass, Eniko Sajti","doi":"10.1038/s41590-025-02217-4","DOIUrl":"10.1038/s41590-025-02217-4","url":null,"abstract":"Bronchopulmonary dysplasia is a common complication of preterm birth, driven in part by the inflammatory effects of supplemental oxygen on the immature lung. Although oxygen therapy is essential, it contributes to disrupted lung development but not all infants are equally susceptible. Using genetically diverse mouse models, we found that hyperoxia-sensitive mice exhibit a distinct innate immune response compared to resilient strains. Notably, the hyperoxia-sensitive C57BL/6J strain showed selective upregulation of TREM2 on lung macrophages and monocytes. Deletion of TREM2 in myeloid cells led to reduced inflammation, preserved alveolar structure and sustained cell proliferation in the developing lung following oxygen exposure. Mechanistically, TREM2 loss limited p53 activation, favoring cell-cycle arrest over apoptosis. These results identify TREM2 as a key driver of immune-mediated lung injury in neonatal hyperoxia and suggest it may be a promising therapeutic target for preventing or treating bronchopulmonary dysplasia in vulnerable preterm infants. Sajti and colleagues identify TREM2 as a critical factor in myeloid cells in response to hyperoxia-induced lung injury in neonates, finding that TREM2 deficiency protects mice from bronchopulmonary dysplasia.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 8","pages":"1287-1298"},"PeriodicalIF":27.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701423","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 transcription complex p52–ETS1 is essential for germinal center formation 转录复合体p52-ETS1对生发中心的形成至关重要

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-07-25 DOI: 10.1038/s41590-025-02236-1

Dhakshayini Morgan, Biyan Zhang, Kerem Fidan, Wenfai Pan, Thamil Selvan Vaiyapuri, Anandhkumar Raju, Dorcas Hei, Ting Yi See, Ita Novita Sari, Jun Wei Chan, Prativa Majee, Akhila Balachander, Jiabo Yu, Ada Hang-Heng Wong, Michelle Meng Huang Mok, Shi Hui Foo, Wei Lin Tang, Nicholas Ang, Ivan Tan, Yan Fen Peng, Patrick Jaynes, Shengli Xu, Gourisankar Ghosh, Shandy Shahabi, Anand D. Jeyasekharan, Masahito Ikawa, Yongliang Zhang, Shanshan Wu Howland, Mai Chan Lau, Vivien Ya-Fan Wang, Kong-Peng Lam, Vinay Tergaonkar

{"title":"The transcription complex p52–ETS1 is essential for germinal center formation","authors":"Dhakshayini Morgan, Biyan Zhang, Kerem Fidan, Wenfai Pan, Thamil Selvan Vaiyapuri, Anandhkumar Raju, Dorcas Hei, Ting Yi See, Ita Novita Sari, Jun Wei Chan, Prativa Majee, Akhila Balachander, Jiabo Yu, Ada Hang-Heng Wong, Michelle Meng Huang Mok, Shi Hui Foo, Wei Lin Tang, Nicholas Ang, Ivan Tan, Yan Fen Peng, Patrick Jaynes, Shengli Xu, Gourisankar Ghosh, Shandy Shahabi, Anand D. Jeyasekharan, Masahito Ikawa, Yongliang Zhang, Shanshan Wu Howland, Mai Chan Lau, Vivien Ya-Fan Wang, Kong-Peng Lam, Vinay Tergaonkar","doi":"10.1038/s41590-025-02236-1","DOIUrl":"10.1038/s41590-025-02236-1","url":null,"abstract":"The NF-κB family comprises five transcription factors (RELA, RELB, C-REL, NF-κB1 (p50) and NF-κB2 (p52)) that form homo- or heterodimers among themselves to regulate gene expression by binding DNA. Here we show that p52 activates transcription without directly binding DNA but as a heterotetrameric complex with ETS1, a transcription factor outside the NF-κB family. By generating a knock-in mouse model (Nfkb2ki/ki) with three mutated residues on p52 required for its interaction with ETS1, but not RELB, we demonstrate that the p52–ETS1 complex regulates the expression of transcription factors OCT1 and OBF1, which are known to be critical for the germinal center program. Consequently, B cell-intrinsic expression of the p52–ETS1 complex was indispensable for splenic germinal center B cell formation and T cell-dependent antibody responses. Functionally, loss of p52–ETS1 interaction led to diminished antigen-specific IgE, thereby protecting mice from allergic responses. Collectively, our findings expand current knowledge of NF-κB signaling and may provide new therapeutic targets for the treatment of allergic diseases. Tergaonkar and colleagues identify a noncanonical interaction between the NF-κB transcription factor family member p52 and the ETS family member ETS1. They find that the p52–ETS1 complex is required for splenic germinal center B cell formation and T cell-dependent antibody responses.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 9","pages":"1553-1566"},"PeriodicalIF":27.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701600","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

How leukocytes push their way through tissues 白细胞是如何穿过组织的

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-07-25 DOI: 10.1038/s41590-025-02242-3

引用次数: 0

Spatial map of microglial diversity beyond proteopathy 超越蛋白质病变的小胶质细胞多样性的空间图

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-07-24 DOI: 10.1038/s41590-025-02205-8

引用次数: 0

Secretogranin 2 binds LILRB4 resulting in immunosuppression 分泌颗粒蛋白2与LILRB4结合导致免疫抑制

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-07-24 DOI: 10.1038/s41590-025-02233-4

Xing Yang, Ryan Huang, Meng Fang, Yubo He, Jingjing Xie, Xiaoye Liu, Chengcheng Zhang, Qi Lou, Mi Deng, Wei Xiong, Cheryl Lewis, Zade Sadek, Ankit Gupta, Lianqi Chen, Xuewu Zhang, Lei Guo, Lin Xu, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

{"title":"Secretogranin 2 binds LILRB4 resulting in immunosuppression","authors":"Xing Yang, Ryan Huang, Meng Fang, Yubo He, Jingjing Xie, Xiaoye Liu, Chengcheng Zhang, Qi Lou, Mi Deng, Wei Xiong, Cheryl Lewis, Zade Sadek, Ankit Gupta, Lianqi Chen, Xuewu Zhang, Lei Guo, Lin Xu, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang","doi":"10.1038/s41590-025-02233-4","DOIUrl":"10.1038/s41590-025-02233-4","url":null,"abstract":"Immunosuppressive myeloid cells are important in a variety of physiological and pathological contexts, including tumor development, but how hormones might regulate their activity is unclear. Secretogranins, a family of secretory proteins in endocrine and neuronal cells, are proposed to function as prohormones or hormones, but their specific receptors are unknown. Here we show that secretogranin 2 (SCG2), a granin family member, functionally interacts with leukocyte immunoglobulin-like receptor B4 (LILRB4) on monocytic cells. Tumor-derived SCG2 promotes tumor growth in myeloid-specific LILRB4 transgenic mice in a T cell-dependent manner, whereas SCG2 deficiency in host mice impairs tumor progression and reduces infiltration of immunosuppressive monocytic cells. Blockade of LILRB4 abrogates SCG2-induced signaling, immunosuppression and tumor growth. Mechanistically, this SCG2–LILRB4 interaction triggers SHP recruitment and SHP-independent STAT3 activation. These findings define a function for SCG2 in regulating monocytic immunosuppression and suggest that the SCG2–LILRB4 axis might be a therapeutic target. Here the authors identify the granin hormone SCG2 as a ligand for the inhibitory receptor LILRB4. They show that SCG2 released from tumors can suppress antitumor immune responses via this interaction, indicating possible therapeutic strategies.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 9","pages":"1567-1580"},"PeriodicalIF":27.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693790","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

Early methionine availability attenuates T cell exhaustion 早期蛋氨酸可用性减弱T细胞耗竭

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-07-23 DOI: 10.1038/s41590-025-02223-6

Piyush Sharma, Ao Guo, Suresh Poudel, Emilio Boada-Romero, Katherine C. Verbist, Gustavo Palacios, Kalyan Immadisetty, Mark J. Chen, Dalia Haydar, Ashutosh Mishra, Junmin Peng, M. Madan Babu, Giedre Krenciute, Evan S. Glazer, Douglas R. Green

{"title":"Early methionine availability attenuates T cell exhaustion","authors":"Piyush Sharma, Ao Guo, Suresh Poudel, Emilio Boada-Romero, Katherine C. Verbist, Gustavo Palacios, Kalyan Immadisetty, Mark J. Chen, Dalia Haydar, Ashutosh Mishra, Junmin Peng, M. Madan Babu, Giedre Krenciute, Evan S. Glazer, Douglas R. Green","doi":"10.1038/s41590-025-02223-6","DOIUrl":"10.1038/s41590-025-02223-6","url":null,"abstract":"T cell receptor (TCR) activation is regulated in many ways, including niche-specific nutrient availability. Here we investigated how methionine (Met) availability and TCR signaling interplay during the earliest events of T cell activation affect subsequent cell fate. Limiting Met during the initial 30 min of TCR engagement increased Ca2+ influx, NFAT1 (encoded by Nfatc2) activation and promoter occupancy, leading to T cell exhaustion. We identified changes in the protein arginine methylome during initial TCR engagement and identified an arginine methylation of the Ca2+-activated potassium transporter KCa3.1, which regulates Ca2+-mediated NFAT1 signaling for optimal activation. Ablation of KCa3.1 arginine methylation increased NFAT1 nuclear localization, rendering T cells dysfunctional in mouse tumor and infection models. Furthermore, acute, early Met supplementation reduced nuclear NFAT1 in tumor-infiltrating T cells and augmented antitumor activity. These findings identify a metabolic event early after T cell activation that affects cell fate. The tumor environment is nutrient deficient. Here the authors show that early availability of methionine is critical for optimal T cell activation and prevents T cell dysfunction, and that dietary methionine can improve the efficacy of cancer immunotherapy in mice.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 8","pages":"1384-1396"},"PeriodicalIF":27.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-025-02223-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcription factors TCF4 and KLF4 respectively control the development of the DC2A and DC2B lineages 转录因子TCF4和KLF4分别控制DC2A和DC2B谱系的发育

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-07-23 DOI: 10.1038/s41590-025-02208-5

Yiwen Zhu, Peiliang Cai, Ziyi Li, Shuangyan Zhang, Wan Ting Kong, Haiting Wang, Fei Gao, Yingying Zeng, Jiawen Qian, Bing Su, Zhaoyuan Liu, Florent Ginhoux

{"title":"Transcription factors TCF4 and KLF4 respectively control the development of the DC2A and DC2B lineages","authors":"Yiwen Zhu, Peiliang Cai, Ziyi Li, Shuangyan Zhang, Wan Ting Kong, Haiting Wang, Fei Gao, Yingying Zeng, Jiawen Qian, Bing Su, Zhaoyuan Liu, Florent Ginhoux","doi":"10.1038/s41590-025-02208-5","DOIUrl":"10.1038/s41590-025-02208-5","url":null,"abstract":"Conventional dendritic cells (cDCs) are a heterogeneous population of professional antigen-presenting cells that bridge innate and adaptive immunity. Many studies in mice have identified various populations of cDCs whose inter-relationships and discrete identities, as well as their link to plasmacytoid DCs (pDCs), have not been cohesively addressed. Here, by combining single-cell sequencing, transcription factor fate-mapping models, conditional knockout models and adoptive transfer, we show that Klf4 expression clearly separates cDC lineage from the pDC lineage, and defined two pre-DC2 subsets: Siglec-H+CD115− pre-DC2s and Siglec-HloCD115+ pre-DC2s. While Siglec-H+CD115− pre-DC2s represent the pDC-like cells that give rise to CD7+CD11blo DC2As in a TCF4-dependent manner, Siglec-HloCD115+ pre-DC2s give rise to CD7−CD11bhi DC2Bs in a KLF4-dependent manner. These data reveal the transcriptional basis of two pre-DC2 subsets and present a firm framework for mouse cDC classification, paving the way for a better understanding of these cells in tissues and in disease. Here Zhu et al. investigate the ontogeny of type 2 dendritic cells (DC2s) in mice. Using Klf4 expression to distinguish conventional DC precursors from plasmacytoid DCs, they identify two pre-DC2 populations with their development controlled by TCF4 and KLF4 that give rise to DC2A and DC2B cells.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 8","pages":"1275-1286"},"PeriodicalIF":27.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684532","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

2B or not 2B is the question in DC ontogeny 2B或不2B是DC个体发生的问题

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-07-23 DOI: 10.1038/s41590-025-02220-9

Venetia Bigley, Matthew Collin

引用次数: 0

LARP4-mediated hypertranslation drives T cell dysfunction in tumors larp4介导的超翻译驱动肿瘤中的T细胞功能障碍

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-07-22 DOI: 10.1038/s41590-025-02232-5

Yi Liu, Haochen Ni, Jie Li, Jing Yang, Ivann Sekielyk, Bryan E. Snow, Zihao Zhang, Feifan Zhang, Michael St. Paul, Jinyi Han, Meghan Kates, Shaofeng Liu, Yawei Zhang, Zurui Huang, Yin Xu, Samuel D. Saibil, Tak W. Mak, Dali Han, Meng Michelle Xu

{"title":"LARP4-mediated hypertranslation drives T cell dysfunction in tumors","authors":"Yi Liu, Haochen Ni, Jie Li, Jing Yang, Ivann Sekielyk, Bryan E. Snow, Zihao Zhang, Feifan Zhang, Michael St. Paul, Jinyi Han, Meghan Kates, Shaofeng Liu, Yawei Zhang, Zurui Huang, Yin Xu, Samuel D. Saibil, Tak W. Mak, Dali Han, Meng Michelle Xu","doi":"10.1038/s41590-025-02232-5","DOIUrl":"10.1038/s41590-025-02232-5","url":null,"abstract":"Adoptive T cell therapies have therapeutic potential for treating solid tumors, but long-term efficacy is limited by reduced functional fitness and poor persistence within the tumor microenvironment. Here we show that intratumoral T cells undergo translatome remodeling, transitioning into a hypertranslational state as they acquire dysfunctional traits. The RNA-binding protein LARP4 is a translation regulator that drives hypertranslation and dysfunction by selectively enhancing the translation of nuclear-encoded oxidative phosphorylation (OXPHOS) mRNAs in exhausted T cells, disrupting OXPHOS subunit balance and causing mitochondrial dysfunction. Knockout of Larp4 in tumor-specific CD8+ T cells reduces hypertranslation, restores mitochondrial function, mitigates exhaustion and enhances effector persistence, resulting in enhanced anti-tumor responses. Additionally, LARP4 knockdown in chimeric antigen receptor T cells prevents terminal exhaustion and improves the response to liquid and solid tumors. This study highlights translation dysregulation as a determinant of T cell dysfunction in tumors. The authors show that LARP4 drives T cell dysfunction in tumors by promoting hypertranslation of oxidative phosphorylation-related mRNAs, resulting in mitochondrial dysfunction. They also target LARP4 to enhance T cell persistence and anti-tumor activity and provide a CAR T cell strategy for treating solid and liquid tumors.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 9","pages":"1488-1500"},"PeriodicalIF":27.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677307","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