Nature Immunology最新文献

Author Correction: Early methionine availability attenuates T cell exhaustion. 作者更正：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 : 2026-05-07 DOI: 10.1038/s41590-026-02534-2

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

引用次数: 0

Sex differences in Alzheimer’s 老年痴呆症的性别差异

IF 27.6 1区医学

Nature Immunology Pub Date : 2026-04-30 DOI: 10.1038/s41590-026-02519-1

Stephanie Houston

引用次数: 0

Whole mouse profiling 全鼠分析

IF 27.6 1区医学

Nature Immunology Pub Date : 2026-04-30 DOI: 10.1038/s41590-026-02518-2

Nicholas J. Bernard

引用次数: 0

The mechanics of LPS recognition 脂多糖识别的机制

IF 27.6 1区医学

Nature Immunology Pub Date : 2026-04-30 DOI: 10.1038/s41590-026-02521-7

Ioana Staicu

引用次数: 0

Cytosolic CTH senses bacterial lipoproteins and drives noncanonical inflammasome activation. 细胞质CTH感知细菌脂蛋白并驱动非典型炎性体激活。

IF 27.6 1区医学

Nature Immunology Pub Date : 2026-04-30 DOI: 10.1038/s41590-026-02511-9

Qiannv Liu, Chunlei Wang, Mengqian Li, Chun Kong, Zijian Zhong, Xiangyun Cheng, Xiangyang Geng, Zhixia Li, Chongyao Zhong, Dong Jiang, Xiuli Sun, Shuo Wang, Pengyan Xia

{"title":"Cytosolic CTH senses bacterial lipoproteins and drives noncanonical inflammasome activation.","authors":"Qiannv Liu, Chunlei Wang, Mengqian Li, Chun Kong, Zijian Zhong, Xiangyun Cheng, Xiangyang Geng, Zhixia Li, Chongyao Zhong, Dong Jiang, Xiuli Sun, Shuo Wang, Pengyan Xia","doi":"10.1038/s41590-026-02511-9","DOIUrl":"https://doi.org/10.1038/s41590-026-02511-9","url":null,"abstract":"Pathogen-associated molecules can have both membrane-associated and intracellular receptors. Bacterial lipoproteins are recognized by Toll-like receptor 2, but it is unclear whether they can also be sensed by cytoplasmic receptors. Here we found that bacterial lipoproteins could be recognized in the cytoplasm of macrophages by cystathionine γ-lyase (CTH) and hydrolyzed into lipid chains containing sulfhydryl groups. The hydrolyzed lipid chains form molecules containing four acylated chains linked through disulfide bonds, which further cleave caspase-11 and activate the noncanonical inflammasome. Changing the redox environment in macrophages affects their recognition of bacterial lipoproteins. CTH-deficient primary and immortalized macrophages do not trigger activation of the noncanonical inflammasome in the presence of intracellular bacterial lipoproteins, while CTH-deficient mice exhibit attenuated immune responses to infection with Staphylococcus aureus and Listeria monocytogenes. Our findings elucidate the molecular mechanisms by which macrophages recognize intracellular bacterial lipoproteins, as well as the regulatory relationship between cellular redox levels and infection resistance.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817912","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

Irisin supports ST2+ Treg cells 鸢尾素支持ST2+ Treg细胞

IF 27.6 1区医学

Nature Immunology Pub Date : 2026-04-30 DOI: 10.1038/s41590-026-02520-8

Laurie A. Dempsey

引用次数: 0

The long noncoding RNA lnc13 restrains inflammatory responses to maintain oral tolerance to gluten. 长链非编码RNA lnc13抑制炎症反应以维持对谷蛋白的口服耐受性。

IF 27.6 1区医学

Nature Immunology Pub Date : 2026-04-30 DOI: 10.1038/s41590-026-02506-6

Ruxiao Yang-Fischer, Alyssa Shearer, Felipe Batista Leão, Izei Pascual-Gonzalez, Arnold Han, Ainara Castellanos-Rubio, Govind Bhagat, Sankar Ghosh

{"title":"The long noncoding RNA lnc13 restrains inflammatory responses to maintain oral tolerance to gluten.","authors":"Ruxiao Yang-Fischer, Alyssa Shearer, Felipe Batista Leão, Izei Pascual-Gonzalez, Arnold Han, Ainara Castellanos-Rubio, Govind Bhagat, Sankar Ghosh","doi":"10.1038/s41590-026-02506-6","DOIUrl":"https://doi.org/10.1038/s41590-026-02506-6","url":null,"abstract":"Celiac disease (CeD) is an autoimmune disorder triggered by dietary gluten. While HLA-DQ2/8-mediated presentation of gliadin peptides is required for disease, the mechanisms that underlie the loss of oral tolerance to gluten remain incompletely understood. Long-noncoding RNAs (lncRNAs) have been increasingly recognized as regulators of immune function, yet their role in oral tolerance has not been previously explored. Here, using a screen designed to identify lncRNAs responsive to T cell activation and enriched for CeD-associated GWAS variants, we identified lnc13 as a top candidate. In HLA-DQ8 transgenic mice lacking lnc13, unmanipulated gluten ingestion led to molecular signatures resembling human CeD and hallmark features of loss of oral tolerance to gluten: increased IFN-γ+ lymphocytes, IL-12+ myeloid cells, cytotoxic intraepithelial immune cells and crypt hyperplasia in the small intestine. Mechanistically, lnc13 binds specific DNA regulatory regions and limits immune cell responsiveness to proinflammatory signals. In particular, lnc13 restrains IL-15-driven differentiation of CD8+ natural killer-like lymphokine-activated killer cells (an IL-15-dependent pathway strongly implicated in CeD). These findings establish lnc13 as a critical noncoding modulator of oral gluten tolerance.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817909","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

Kupffer cell calibration of T cell responses via VSIG4-CD5 interaction promotes tumor evasion. 通过VSIG4-CD5相互作用对T细胞应答进行Kupffer细胞校准，促进肿瘤逃逸。

IF 27.6 1区医学

Nature Immunology Pub Date : 2026-04-29 DOI: 10.1038/s41590-026-02510-w

Xia Zhou, Wei Liu, Jing Hu, Qi Yao, Futing Zhang, Qi Wu, Liya Li, Jiajia Li, Lixia Zhu, Chen Chen, Qing Zhang, Renjie Zhang, Jinling Liu, Chaowei Shi, Hong Zhou, Ao Guo, Jian Wang, Jizhou Wang, Qingsong Hu, Lu Li, Tengchuan Jin, Zhutian Zeng

{"title":"Kupffer cell calibration of T cell responses via VSIG4-CD5 interaction promotes tumor evasion.","authors":"Xia Zhou, Wei Liu, Jing Hu, Qi Yao, Futing Zhang, Qi Wu, Liya Li, Jiajia Li, Lixia Zhu, Chen Chen, Qing Zhang, Renjie Zhang, Jinling Liu, Chaowei Shi, Hong Zhou, Ao Guo, Jian Wang, Jizhou Wang, Qingsong Hu, Lu Li, Tengchuan Jin, Zhutian Zeng","doi":"10.1038/s41590-026-02510-w","DOIUrl":"https://doi.org/10.1038/s41590-026-02510-w","url":null,"abstract":"Liver metastases can resist T cell immunotherapies, indicating an adaptation of metastatic tumors toward reduced immunogenicity in the liver. Here we show that VSIG4, an immune checkpoint molecule predominantly expressed by Kupffer cells, has an opposing function in determining the growth of liver metastases with distinct antigenicity by modulating cognate T cell antigen receptor signaling through an interaction with CD5. VSIG4-CD5 engagement impedes activation of low-affinity CD8+ T cells while enhancing responses of high-affinity CD8+ T cells by rescuing them from activation-induced cell death. This bidirectional regulation favors the outgrowth of poorly immunogenic metastatic tumor clones and fosters an immune landscape that is unfavorable to T cells as metastatic liver cancer progresses. We also show that blockade of VSIG4-CD5 interaction using a nanoantibody to VSIG4 sensitizes liver metastases to anti-PD-L1 therapy, achieving synergistic efficacy in mice. These findings provide mechanistic insights into cancer immunoediting during liver metastasis and a possible approach for treating immunologically cold tumors.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777044","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

A spatially coordinated keratinocyte–fibroblast circuit recruits MMP9⁺ myeloid cells to drive type I interferon-driven inflammation in photosensitive autoimmunity 在光敏自身免疫中，一个空间协调的角化细胞-成纤维细胞回路招募MMP9 +髓样细胞来驱动I型干扰素驱动的炎症

IF 30.5 1区医学

Nature Immunology Pub Date : 2026-04-24 DOI: 10.1038/s41590-026-02502-w

Yuqing Wang, Khashayar Afshari, Nazgol-Sadat Haddadi, Carolina Salomão Lopes, Chee-Huat Linus Eng, Leah M. Whiteman, Nuria Martinez, Pyae P. Kyawe, Ksenia S. Anufrieva, Kevin Wei, Kirsten Frieda, Misha Rosenbach, Ruth Ann Vleugels, Stefania Gallucci, John E. Harris, Mehdi Rashighi, Manuel Garber

{"title":"A spatially coordinated keratinocyte–fibroblast circuit recruits MMP9⁺ myeloid cells to drive type I interferon-driven inflammation in photosensitive autoimmunity","authors":"Yuqing Wang, Khashayar Afshari, Nazgol-Sadat Haddadi, Carolina Salomão Lopes, Chee-Huat Linus Eng, Leah M. Whiteman, Nuria Martinez, Pyae P. Kyawe, Ksenia S. Anufrieva, Kevin Wei, Kirsten Frieda, Misha Rosenbach, Ruth Ann Vleugels, Stefania Gallucci, John E. Harris, Mehdi Rashighi, Manuel Garber","doi":"10.1038/s41590-026-02502-w","DOIUrl":"https://doi.org/10.1038/s41590-026-02502-w","url":null,"abstract":"Photosensitivity is central to cutaneous lupus erythematosus and dermatomyositis (DM), but the mechanisms linking UVB exposure to tissue-specific autoimmunity are poorly defined. Using single-cell RNA sequencing, spatial transcriptomics, proteomics, UVB provocation and in vitro modeling, we identify MMP9⁺CD14⁺ myeloid cells as critical mediators of photosensitivity. These cells expand significantly in lesional skin, produce interferon-β (IFNβ) and colocalize with cytotoxic CD4⁺ T cells at the dermal–epidermal junction. Keratinocytes activate fibroblasts in the superficial dermis, prompting them to release chemokines (CCL2, CCL19, CCL7, CCL8) that recruit MMP9⁺CD14⁺ cells. In vitro, type I interferon-primed keratinocytes exposed to UVB release cytokines activating dendritic cells, mirroring in vivo responses. UVB irradiation of non-lesional skin of patients with DM rapidly recruits these myeloid cells. In a clinical proof-of-concept study, anti-type I interferon treatment with anifrolumab prevented UVB-induced myeloid infiltration and reduced photosensitivity. Therefore, targeting MMP9⁺CD14⁺ cells may offer therapeutic potential for managing photosensitive autoimmune skin conditions.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"23 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751845","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

IL-9 and Blimp-1 protect the transcriptional identity of group 2 innate lymphocytes in allergic asthma IL-9和Blimp-1保护过敏性哮喘2组先天淋巴细胞的转录特性

IF 30.5 1区医学

Nature Immunology Pub Date : 2026-04-24 DOI: 10.1038/s41590-026-02509-3

Yibo Zheng, Shilpi Giri, Jinyi Zhang, Yijia Chen, Aaron Yang, Sagar L. Kale, Harshita Beeravolu, Abbe Pannucci, Anthony D. Marinov, Jeremy S. Tilstra, Kun He, Arianna Creech, Daniella M. Schwartz, Rachel A. Gottschalk, Nicolas Bouladoux, Yasmine Belkaid, Anthony R. Cillo, Anuradha Ray, Amanda C. Poholek

{"title":"IL-9 and Blimp-1 protect the transcriptional identity of group 2 innate lymphocytes in allergic asthma","authors":"Yibo Zheng, Shilpi Giri, Jinyi Zhang, Yijia Chen, Aaron Yang, Sagar L. Kale, Harshita Beeravolu, Abbe Pannucci, Anthony D. Marinov, Jeremy S. Tilstra, Kun He, Arianna Creech, Daniella M. Schwartz, Rachel A. Gottschalk, Nicolas Bouladoux, Yasmine Belkaid, Anthony R. Cillo, Anuradha Ray, Amanda C. Poholek","doi":"10.1038/s41590-026-02509-3","DOIUrl":"https://doi.org/10.1038/s41590-026-02509-3","url":null,"abstract":"Allergic asthma is driven by type 2 immune responses, including type 2 innate lymphoid cells (ILC2s). Although ILC2s are activated by the tissue alarmins interleukin (IL)-33 and IL-25, these signals do not intrinsically enforce type 2 identity and the mechanisms that maintain type 2 cytokine expression remain unclear. Here we show that allergen-induced IL-33 and IL-25 rapidly induce IL-9, which in turn upregulates the transcriptional repressor Blimp-1 in ILC2s. Blimp-1 sustains type 2 immunity by directly repressing type 1 inflammatory programs, including expression of interferon-γ and tumor necrosis factor. Deletion of Blimp-1 in ILC2s increased type 1 cytokine production and reduced IL-5 and IL-13 expression, eosinophil recruitment and mucus production in the lung. In contrast, IL-9 expression was enhanced in the absence of Blimp-1, leading to increased mast cell recruitment. Together, these findings identify Blimp-1 as a key regulator of ILC2 transcriptional fidelity that stabilizes type 2 inflammation while constraining divergent inflammatory programs during allergic responses.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"250 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751846","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