Nature Immunology最新文献_第10页

Rediscovering eosinophil identity through tissue adaptation 通过组织适应重新发现嗜酸性粒细胞身份。

IF 26.5 1区医学

Nature Immunology Pub Date : 2026-07-10 DOI: 10.1038/s41590-026-02593-5

Svetoslav Chakarov, Heping Xu

{"title":"Rediscovering eosinophil identity through tissue adaptation","authors":"Svetoslav Chakarov, Heping Xu","doi":"10.1038/s41590-026-02593-5","DOIUrl":"10.1038/s41590-026-02593-5","url":null,"abstract":"Eosinophils are now recognized as multifunctional immune cells that contribute to tissue homeostasis, repair, metabolism and host defense in addition to fulfilling their established roles in type 2 immunity and allergic disease. Substantial eosinophil heterogeneity is evident across tissues and inflammatory states, challenging the view that eosinophils are a uniform population of short-lived effector granulocytes. Here we discuss the current understanding of eosinophil development, tissue adaptation and functional specialization across organs and disease contexts. We propose an integrated framework in which eosinophil identity is shaped by four interdependent axes: differentiation and lineage commitment; local environmental cues; time of tissue residence; and inflammatory status. Together, these factors generate eosinophil states that are dynamic, context dependent and continuously tuned to their tissue environment. Viewing eosinophils through this multidimensional lens reframes these cells as adaptable participants in tissue physiology, rather than solely as terminal effectors of type 2 immunity. In this Review, the authors discuss the immunology of eosinophils beyond their roles in allergy and type 2 immune responses, focusing on the adaptation and heterogeneity of these cells in different tissues and inflammatory contexts.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 8","pages":"1563-1576"},"PeriodicalIF":26.5,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148415901","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

In tuberculosis, the neutrophil is neutral in name alone 在结核病中，嗜中性粒细胞本身就是中性的。

IF 26.5 1区医学

Nature Immunology Pub Date : 2026-07-09 DOI: 10.1038/s41590-026-02586-4

David G. Russell

引用次数: 0

ALOX15 orchestrates mitochondrial antiviral immunity and serves as a host target for anti-influenza therapy ALOX15协调线粒体抗病毒免疫，并作为抗流感治疗的宿主靶点。

IF 26.5 1区医学

Nature Immunology Pub Date : 2026-07-08 DOI: 10.1038/s41590-026-02584-6

Jing-Yu Weng, Xin-Xing Chen, Hui-Er Ye, Ying-Ying Zeng, Wan-Li Liang, Yin-Ci Zhang, Xin-Yu Zong, Chang-Yu Yan, Yue Ye, Yan-Ping Wu, Wan-Yang Sun, Wen-Jun Duan, Lei Liang, Yuqi Yan, Yun-Feng Cao, Yi Dai, Hiroshi Kurihara, Hao Gao, Shu-Hua Ouyang, Yi-Fang Li, Rong-Rong He

{"title":"ALOX15 orchestrates mitochondrial antiviral immunity and serves as a host target for anti-influenza therapy","authors":"Jing-Yu Weng, Xin-Xing Chen, Hui-Er Ye, Ying-Ying Zeng, Wan-Li Liang, Yin-Ci Zhang, Xin-Yu Zong, Chang-Yu Yan, Yue Ye, Yan-Ping Wu, Wan-Yang Sun, Wen-Jun Duan, Lei Liang, Yuqi Yan, Yun-Feng Cao, Yi Dai, Hiroshi Kurihara, Hao Gao, Shu-Hua Ouyang, Yi-Fang Li, Rong-Rong He","doi":"10.1038/s41590-026-02584-6","DOIUrl":"10.1038/s41590-026-02584-6","url":null,"abstract":"Viral infections trigger cellular stress responses, and host stress proteins play key roles in antiviral defense. Here we identify stress-responsive protein arachidonate lipoxygenase-15 (ALOX15) is a critical component of mitochondrial antiviral innate immunity. Loss of Alox15 impairs mitochondrial antiviral signaling (MAVS)-mediated type I interferon production, resulting in increased susceptibility to influenza virus, an effect reversed by adeno-associated virus-mediated lung delivery of Alox15. ALOX15 translocates to mitochondria in response to H1N1 and other RNA viruses (H3N2 and human coronavirus-229E), independent of its enzymatic activity. This mitochondrial localization is also strikingly observed in peripheral blood mononuclear cells from influenza-infected individuals. Mechanistically, ALOX15 is recruited to mitochondria by polymerized MAVS, displacing the deubiquitinase USP19 and sustaining MAVS K63-linked ubiquitination and aggregation. Leveraging these insights, we developed a synergistic ALOX15 regulation-based therapeutic strategy for influenza infection by combining the ALOX15 transcriptional activator songorine with its enzymatic inhibitor PD146176. Together, our findings establish ALOX15 as an essential component of mitochondrial antiviral immunity and a promising host-directed target for antiviral therapy. ALOX15 translocates to mitochondria under RNA virus stress, and orchestrates MAVS innate immunity in a nonenzymatic manner, identifying ALOX15 as a host-directed target for anti-influenza therapy.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 8","pages":"1604-1618"},"PeriodicalIF":26.5,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408340","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

Implications of RNA virus persistence for post-acute sequelae and chronic inflammatory syndromes RNA病毒持续存在对急性后后遗症和慢性炎症综合征的影响

IF 26.5 1区医学

Nature Immunology Pub Date : 2026-07-07 DOI: 10.1038/s41590-026-02577-5

Daniela Vidal, Ítalo de Araújo Castro, Carolina B. López

{"title":"Implications of RNA virus persistence for post-acute sequelae and chronic inflammatory syndromes","authors":"Daniela Vidal, Ítalo de Araújo Castro, Carolina B. López","doi":"10.1038/s41590-026-02577-5","DOIUrl":"10.1038/s41590-026-02577-5","url":null,"abstract":"Viral persistence refers to the ability of a virus to remain in its host for an extended period. Although most non-retroviral RNA viruses are traditionally known for causing acute, self-limiting infections, accumulating evidence of the detection of viral products long after the infectious virus is cleared suggests that RNA viruses can establish persistent infections. Persistent viral products include replication-competent viral genomes, viral proteins, mutated viruses or non-standard viral genomes. The persistence of viral products entails a continuous interaction with the host and is often associated with prolonged tissue inflammation and chronic disease. Here, we discuss emerging evidence of the persistence of viral products from viruses commonly considered to cause acute infections. We explore the known requirements for virus persistence and the implications for the development of post-acute sequelae and predisposition to chronic inflammatory syndromes. López and colleagues review recent evidence of RNA virus persistence and the associated consequences in terms of post-acute sequelae or chronic inflammatory syndromes.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 8","pages":"1553-1562"},"PeriodicalIF":26.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-026-02577-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400708","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

Tissue-resident CD8+ T cells link pregnancy to breast cancer protection 组织常驻CD8+ T细胞将怀孕与乳腺癌保护联系起来。

IF 26.5 1区医学

Nature Immunology Pub Date : 2026-07-07 DOI: 10.1038/s41590-026-02580-w

引用次数: 0

Exhausted CD8+ T cell subsets differ a TAD 耗竭的CD8+ T细胞亚群不同于TAD。

IF 26.5 1区医学

Nature Immunology Pub Date : 2026-07-06 DOI: 10.1038/s41590-026-02583-7

Maegan K. Murphy, Takeshi Egawa

引用次数: 0

Mapping self-associating chromatin hubs identifies Id proteins as key determinants of exhausted CD8+ T cell fate 绘制自相关的染色质枢纽，确定Id蛋白是耗尽CD8+ T细胞命运的关键决定因素。

IF 26.5 1区医学

Nature Immunology Pub Date : 2026-07-06 DOI: 10.1038/s41590-026-02578-4

Wei Hu, Qing Chen, Shaoqi Zhu, Shengen Shawn Hu, Haibo Yu, Vanita Patel, Ying Wang, Vladimir P. Badovinac, Yi Zhang, Chongzhi Zang, Weiqun Peng, Hai-Hui Xue

{"title":"Mapping self-associating chromatin hubs identifies Id proteins as key determinants of exhausted CD8+ T cell fate","authors":"Wei Hu, Qing Chen, Shaoqi Zhu, Shengen Shawn Hu, Haibo Yu, Vanita Patel, Ying Wang, Vladimir P. Badovinac, Yi Zhang, Chongzhi Zang, Weiqun Peng, Hai-Hui Xue","doi":"10.1038/s41590-026-02578-4","DOIUrl":"10.1038/s41590-026-02578-4","url":null,"abstract":"Within days of exposure to chronic viral infections, activated CD8+ T cells differentiate into Tcf1−Slamf6loTim3hi exhaustion-prone effector T (TEX_EFF) cells or self-renewing Tcf1+Slamf6hiTim3lo precursor exhausted T (TPEX) cells. Here we showed that early CD8+ TEX cell fates were imprinted by forming subset-specific, self-associating chromatin hubs. Chromatin hub assembly coincided with effector or stemness gene induction and identified the transcription cofactors Id2 and Id3 as key regulators that promoted CD8+ TEX_EFF and CD8+ TPEX cell fates, respectively. Id2 drove CD8+ TEX_EFF cell specification by activating effector genes, while suppressing genes involved in exhaustion and stemness. In contrast, Id3-repressed effector genes but upregulated IL-7Rα and AhR, thereby maintaining the CD8+ TPEX cell pool. Mechanistically, Id2 and Id3 exhibited a distinct impact on the chromatin accessibility landscape in early CD8+ TEX cells by engaging Runx3 and Tcf1 transcription factors along with E proteins. These findings indicated that reshaping chromatin architecture represents a critical means for specifying CD8+ TEX cell fates and ensuring lineage stability. Xue et al. describe the dynamics of chromatin architecture during exhausted CD8+ T cell fate decisions and identify Id proteins as key regulators.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 8","pages":"1678-1692"},"PeriodicalIF":26.5,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393382","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

Exhausted CD8+ T cell fate is programmed by dynamic CTCF-mediated enhancer activation and invariant CTCF-imposed barriers 耗尽的CD8+ T细胞的命运是通过动态ctcf介导的增强子激活和不变的ctcf施加的屏障来编程的。

IF 26.5 1区医学

Nature Immunology Pub Date : 2026-07-06 DOI: 10.1038/s41590-026-02585-5

Wei Hu, Shaoqi Zhu, Qing Chen, Vladimir P. Badovinac, Weiqun Peng, Hai-Hui Xue

{"title":"Exhausted CD8+ T cell fate is programmed by dynamic CTCF-mediated enhancer activation and invariant CTCF-imposed barriers","authors":"Wei Hu, Shaoqi Zhu, Qing Chen, Vladimir P. Badovinac, Weiqun Peng, Hai-Hui Xue","doi":"10.1038/s41590-026-02585-5","DOIUrl":"10.1038/s41590-026-02585-5","url":null,"abstract":"Exhausted CD8+ T (TEX) cells undergo extensive genome reorganization during differentiation, yet the drivers of this process remain elusive. Here we show that CTCF programmed CD8+ TEX cell fates through two distinct modes of action. CTCF acquired de novo binding sites and concordantly induced open chromatin in early CD8+ TEX cells responding to chronic viral infection. The dynamic CTCF binding activated enhancers and promoted chromatin looping. Consequently, genetic ablation of CTCF diminished chromatin accessibility and interaction strength, impairing CD8+ TEX cell proliferation, effector function and bioenergetic mobilization. Conversely, invariant CTCF binding acted as essential chromatin barriers, and loss of CTCF disrupted insulation and caused aberrant chromatin self-association and undue RNA polymerase II pausing, leading to excessive activation of exhaustion- and stemness-linked genes. Thus, CTCF balanced CD8+ TEX cell differentiation by gaining dynamic binding to induce cytotoxicity and sustain metabolic fitness, while its invariant binding compartmentalized exhaustion and stemness program genes to prevent their overexuberant activation. Xue and colleagues show that the chromatin regulator CTCF balances stemness preservation and effector differentiation to specify CD8+ TPEX versus CD8+ TEX_EFF cell fate decisions.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 8","pages":"1693-1707"},"PeriodicalIF":26.5,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393375","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

Author Correction: An atlas of genetic effects on cellular composition of the tumor microenvironment 作者更正：肿瘤微环境中细胞组成的遗传效应图谱。

IF 26.5 1区医学

Nature Immunology Pub Date : 2026-07-06 DOI: 10.1038/s41590-026-02602-7

Yimin Cai, Zequn Lu, Can Chen, Ying Zhu, Zhirui Chen, Zuyou Wu, Jingyi Peng, Xuanyu Zhu, Ziying Liu, Bin Li, Ming Zhang, Jinyu Huang, Yanmin Li, Yizhuo Liu, Qianying Ma, Chunyi He, Shuoni Chen, Wen Tian, Linyun Fan, Caibo Ning, Hui Geng, Bin Xu, Haijie Li, Xu Zhu, Jun Fang, Xiaoyang Wang, Shaokai Zhang, Meng Jin, Chaoqun Huang, Xiaojun Yang, Jianbo Tian, Xiaoping Miao

引用次数: 0

Mechanosensing by T cells promotes a tissue-resident memory transcriptional program T细胞的机械感应促进了组织驻留记忆转录程序。

IF 26.5 1区医学

Nature Immunology Pub Date : 2026-07-03 DOI: 10.1038/s41590-026-02581-9

Jérémy Postat, Mauricio Merino, Angela R. Mingarelli, Aysha Cerf, Aanya Bhagrath, Dhanesh Patel, Connie Shen, Johanna Brodbeck, Pouria Tirgar, Dakota Rogers, Jules Blanc, Thiviya Jeyakumar, Caitlin Schneider, Shana Coley, Nadia Giannetti, Taylor A. DePauw, Johannes Textor, Allen Ehrlicher, Stephen C. Jameson, Reza Sharif-Naeini, Abhinav Sharma, Judith N. Mandl

{"title":"Mechanosensing by T cells promotes a tissue-resident memory transcriptional program","authors":"Jérémy Postat, Mauricio Merino, Angela R. Mingarelli, Aysha Cerf, Aanya Bhagrath, Dhanesh Patel, Connie Shen, Johanna Brodbeck, Pouria Tirgar, Dakota Rogers, Jules Blanc, Thiviya Jeyakumar, Caitlin Schneider, Shana Coley, Nadia Giannetti, Taylor A. DePauw, Johannes Textor, Allen Ehrlicher, Stephen C. Jameson, Reza Sharif-Naeini, Abhinav Sharma, Judith N. Mandl","doi":"10.1038/s41590-026-02581-9","DOIUrl":"10.1038/s41590-026-02581-9","url":null,"abstract":"Cell migration and strategic positioning within tissues is critical for the rapid mobilization of a T cell response. T cells must remain motile in both lymphoid and nonlymphoid tissues, which vary widely in mechanical properties such as stiffness. Here we showed that activated T cells sensed mechanical cues and responded with changes in cell morphology, nuclear envelope composition and initiation of DNA repair to protect their genomic material from force-mediated damage. Increased mechanical input also drove the transcriptional reprogramming of activated T cells, including changes in many of the core genes shared by tissue-resident memory T cells across diverse tissues, by modulating the expression of the tissue-resident memory T cell-associated transcription factors Klf2, Runx3 and Hic1. Thus, mechanosensing by activated T cells impacted T cell fate, promoting a transcriptional program associated with tissue residency. Mandl and colleagues show that increased mechanical input drives transcriptional changes associated with a core tissue-resident program in activated CD8+ T cells.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 8","pages":"1708-1721"},"PeriodicalIF":26.5,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-026-02581-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379748","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