Nature Immunology最新文献_第2页

Skin fibroblasts sculpt distinct stromal and immune niches across diseases 皮肤成纤维细胞在疾病中塑造出不同的基质和免疫龛。

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-09-24 DOI: 10.1038/s41590-025-02266-9

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Spatial and functional diversity of innate lymphoid cells in the human female genital tract may contribute to antiviral responses to HIV. 人类女性生殖道先天淋巴样细胞的空间和功能多样性可能有助于对HIV的抗病毒反应。

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-09-22 DOI: 10.1038/s41590-025-02285-6

Alexandra Werner,Laura Moreno de Lara,Aleah Holmes,Siddharth Parthasarathy,Genna E Moldovan,Anna Borchers,Francisco J Carrillo-Salinas,Jared M Fortier,Vidya Iyer,Alison Vogell,Rebecca Jameson,Jacquelyn Stephens,Marta Rodriguez-Garcia

{"title":"Spatial and functional diversity of innate lymphoid cells in the human female genital tract may contribute to antiviral responses to HIV.","authors":"Alexandra Werner,Laura Moreno de Lara,Aleah Holmes,Siddharth Parthasarathy,Genna E Moldovan,Anna Borchers,Francisco J Carrillo-Salinas,Jared M Fortier,Vidya Iyer,Alison Vogell,Rebecca Jameson,Jacquelyn Stephens,Marta Rodriguez-Garcia","doi":"10.1038/s41590-025-02285-6","DOIUrl":"https://doi.org/10.1038/s41590-025-02285-6","url":null,"abstract":"Innate lymphoid cells (ILCs) are tissue-resident lymphocytes specialized in cytokine secretion that lack antigen-specific receptors. The contribution of ILCs to antiviral mucosal immunity in humans, particularly in the female genital tract (FGT), remains unexplored. Here we resolved human FGT ILC diversity by spectral flow cytometry and CITE-seq, spatial location within genital anatomical regions using ChipCytometry, and determined homeostatic function and antiviral responses. We uncovered spatial and functional specializations of genital ILC subsets under homeostasis, with compartmentalized age-related and pregnancy-related changes. CD161 expression differentially discriminated ILC subsets preloaded with cytokines at steady state. We identified a unique NKp44+CCR6+ ILC3 subset in the endometrium that actively degranulated at homeostasis and was located in lymphoid aggregates surrounded by B cells and T cells. By contrast, ILC1s were found scattered, enriched in the ectocervix and located close to the epithelium. Following in vitro HIV stimulation, genital ILCs displayed rapid subset-specific antiviral responses. These findings reveal distinct tissue and subset-specific features of FGT ILCs and their capacity to immediately respond to viral stimuli, providing a foundation for future studies to determine the potential role of ILCs in mucosal immune protection in the FGT.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"41 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117054","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}

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Precise inhibition of pyroptotic pores presents new opportunities for inflammation therapy 精确抑制热腐毛孔为炎症治疗提供了新的机会。

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-09-19 DOI: 10.1038/s41590-025-02294-5

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STING signals to NF-κB from late endolysosomal compartments using IRF3 as an adaptor. 利用IRF3作为接头，STING信号从内溶酶体晚期腔室传递给NF-κB。

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-09-19 DOI: 10.1038/s41590-025-02283-8

Bao-Cun Zhang,Alice Pedersen,Line S Reinert,Ying Li,Ryo Narita,Manja Idorn,Lili Hu,Morten K Skouboe,Sirui Li,Muyesier Maimaitili,Xiangning Ding,Yingying Cong,Jian Zhao,Marie-Louise Frémond,Kasper Mikkelsen,Zongliang Gao,Jin-Rong Huang,Emil A Thomsen,Jakob H Mikkelsen,Rajan Venkatraman,Martin K Thomsen,Marie B Iversen,Sonia Assil,Ran Zhang,Linda Henneman,Martin R Jakobsen,Claus Oxvig,Tina S Dalgaard,Peter Møller,Angela Fago,Tobias Wang,Christian B F Andersen,Dominic De Nardo,Fulvio Reggiori,Jenny P-Y Ting,Jacob G Mikkelsen,Rasmus O Bak,Trine H Mogensen,Pingwei Li,Søren R Paludan

{"title":"STING signals to NF-κB from late endolysosomal compartments using IRF3 as an adaptor.","authors":"Bao-Cun Zhang,Alice Pedersen,Line S Reinert,Ying Li,Ryo Narita,Manja Idorn,Lili Hu,Morten K Skouboe,Sirui Li,Muyesier Maimaitili,Xiangning Ding,Yingying Cong,Jian Zhao,Marie-Louise Frémond,Kasper Mikkelsen,Zongliang Gao,Jin-Rong Huang,Emil A Thomsen,Jakob H Mikkelsen,Rajan Venkatraman,Martin K Thomsen,Marie B Iversen,Sonia Assil,Ran Zhang,Linda Henneman,Martin R Jakobsen,Claus Oxvig,Tina S Dalgaard,Peter Møller,Angela Fago,Tobias Wang,Christian B F Andersen,Dominic De Nardo,Fulvio Reggiori,Jenny P-Y Ting,Jacob G Mikkelsen,Rasmus O Bak,Trine H Mogensen,Pingwei Li,Søren R Paludan","doi":"10.1038/s41590-025-02283-8","DOIUrl":"https://doi.org/10.1038/s41590-025-02283-8","url":null,"abstract":"NF-κB is central for activation of immune responses. Cytosolic DNA activates the cGAS-STING pathway to induce type I interferons (IFNs) and signaling through NF-κB, thus instigating host defenses and pathological inflammation. However, the mechanism underlying STING-induced NF-κB activation is unknown. Here we report that STING activates NF-κB in a delayed manner, following exit from the Golgi to endolysosomal compartments. Activation of NF-κB is dependent on the IFN-inducing transcription factor IRF3 but is independent of type I IFN signaling. This activation pattern is evolutionarily conserved in tetrapods. Mechanistically, the monomer IRF3 is recruited to STING pS358, with delayed kinetics relative to IRF3 recruitment to STING pS366, which promotes type I IFN responses. IRF3 engagement with STING pS358 induces trafficking to late endolysosomal compartments, supporting recruitment of TRAF6 and activation of NF-κB. We identify a TRAF6 binding motif in IRF3 that facilitates recruitment of TRAF6. This work defines a signaling surface on STING and a function for IRF3 as an adaptor in immune signaling. These findings indicate that STING signaling to NF-κB is enabled only within a short time window between exit from the Golgi and lysosomal degradation, possibly limiting inflammation under homeostatic and danger-sensing conditions.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"20 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089752","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

DNA hypomethylation primes ILC lineage choice DNA低甲基化引发ILC谱系选择。

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-09-18 DOI: 10.1038/s41590-025-02275-8

Noah Gamble, Michelle Sun, Andrew S. Koh

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Epigenetic imprinting in innate lymphoid cell precursors directs the lineage segregation of innate lymphoid cells 先天淋巴样细胞前体的表观遗传印迹指导先天淋巴样细胞的谱系分离。

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-09-18 DOI: 10.1038/s41590-025-02261-0

Zhen Liu, Fei Shao, Qiang Zhang, Min Zhao, Shuai Gao, Xusheng Zhang, Dou Yu, Jingyao Zhang, Pengyan Xia, Shuo Wang

{"title":"Epigenetic imprinting in innate lymphoid cell precursors directs the lineage segregation of innate lymphoid cells","authors":"Zhen Liu, Fei Shao, Qiang Zhang, Min Zhao, Shuai Gao, Xusheng Zhang, Dou Yu, Jingyao Zhang, Pengyan Xia, Shuo Wang","doi":"10.1038/s41590-025-02261-0","DOIUrl":"10.1038/s41590-025-02261-0","url":null,"abstract":"Innate lymphoid cells (ILCs) are essential for mucosal homeostasis, but the epigenetic regulation of their lineage segregation remains elusive. Here we simultaneously profiled the single-cell DNA methylome, chromatin accessibility and transcriptome of ILC subsets and ILC precursors (ILCPs) and found that ILCPs could be divided into two subgroups (ILCP1 and ILCP2). ILCP2s had highly heterogeneous DNA methylation profiles and could be divided into three groups according to their DNA methylation characteristics, which matched those of ILC subsets. We identified the signature methylation regions (SMRs) of each ILC subset and traced the DNA methylation imprinting during ILCP differentiation. ILCP2s with hypomethylated SMRs characteristic of ILC subsets differentiated into those subsets. DNA methylation editing of SMRs suppressed ILC lineage segregation, while deletion of Dnmt1 in ILCPs abrogated the heterogeneous distribution of SMRs and resulted in ILC differentiation defects. These findings provide evidence that epigenetic imprinting determines lineage segregation during immune cell development. Wang and colleagues show that specific DNA methylation profiles mark the ILC progenitors (ILCP) that would differentiate into ILC1, ILC2 or ILC3 subsets.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 10","pages":"1686-1698"},"PeriodicalIF":27.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083397","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}

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Publisher Correction: The pre-T cell receptor as a tumor immunotherapy target in T cell leukemia 发布者更正：前T细胞受体作为T细胞白血病的肿瘤免疫治疗靶点

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-09-16 DOI: 10.1038/s41590-025-02306-4

Aliza Rosen, Iannis Aifantis

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Microbiota-mediated mechanisms of mucosal immunity across the lifespan 微生物群介导的粘膜免疫机制贯穿整个生命周期

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-09-16 DOI: 10.1038/s41590-025-02281-w

Iliyan D. Iliev, J. Magarian Blander, Nicholas Collins, Chun-Jun Guo, Randy S. Longman, Gregory F. Sonnenberg, Melody Y. Zeng, David Artis

{"title":"Microbiota-mediated mechanisms of mucosal immunity across the lifespan","authors":"Iliyan D. Iliev, J. Magarian Blander, Nicholas Collins, Chun-Jun Guo, Randy S. Longman, Gregory F. Sonnenberg, Melody Y. Zeng, David Artis","doi":"10.1038/s41590-025-02281-w","DOIUrl":"10.1038/s41590-025-02281-w","url":null,"abstract":"The microbiota has a fundamental role in regulating homeostasis and inflammation across the barrier surfaces of the body. The gut is a unique bioreactor where the high concentration of microorganisms, microbial and dietary metabolites, microbial-derived molecular structures, immune cells, stroma and neurons form a complex, highly interactive and precisely regulated system. The mucosal immune system in the gut has profound local and systemic effects, influencing both health and disease. A critical period of immune imprinting occurs early in life, shaped by the neonatal microbiota and nutrition, to influence immune development and long-term disease susceptibility. Microbiota-derived metabolites have crucial roles in immune modulation, influencing epithelial integrity, oral tolerance and inflammatory responses. This Review explores the interactions between the microbiota and the mucosal immune system from infancy to adulthood, highlighting the impact on health and disease. We also discuss therapeutic interventions, including microbiota-derived molecules, dietary metabolites and emerging microbiome-based co-therapies. Here Iliev et al. review the interactions between the microbiota and the mucosal immune system from infancy to adulthood, highlighting the impact on health and disease.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 10","pages":"1645-1659"},"PeriodicalIF":27.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067919","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

TFH cell programs by pathogen and species TFH细胞受病原体和物种的影响

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-09-16 DOI: 10.1038/s41590-025-02284-7

Amy S. Weinmann, Danielle A. Chisolm

引用次数: 0

Lymph nodes fuel KLF2-dependent effector CD8+ T cell differentiation during chronic infection and checkpoint blockade 慢性感染和检查点阻断期间，淋巴结燃料klf2依赖性效应CD8+ T细胞分化

IF 27.6 1区医学

Nature Immunology Pub Date : 2025-09-15 DOI: 10.1038/s41590-025-02276-7

Carlson Tsui, Leonie Heyden, Lifen Wen, Catarina Gago da Graça, Nikita Potemkin, Aleksej Frolov, Daniel Rawlinson, Lei Qin, Verena C. Wimmer, Marjan Hadian-Jazi, Darya Malko, Chun-Hsi Su, Sining Li, Kayla R. Wilson, Helena Horvatic, Sharanya K. Wijesinghe, Marcela L. Moreira, Lachlan Dryburgh, Dominik Schienstock, Lisa Rausch, Daniel T. Utzschneider, Cornelia Halin, Scott N. Mueller, Marc D. Beyer, Sammy Bedoui, Zeinab Abdullah, Jan Schröder, Axel Kallies

{"title":"Lymph nodes fuel KLF2-dependent effector CD8+ T cell differentiation during chronic infection and checkpoint blockade","authors":"Carlson Tsui, Leonie Heyden, Lifen Wen, Catarina Gago da Graça, Nikita Potemkin, Aleksej Frolov, Daniel Rawlinson, Lei Qin, Verena C. Wimmer, Marjan Hadian-Jazi, Darya Malko, Chun-Hsi Su, Sining Li, Kayla R. Wilson, Helena Horvatic, Sharanya K. Wijesinghe, Marcela L. Moreira, Lachlan Dryburgh, Dominik Schienstock, Lisa Rausch, Daniel T. Utzschneider, Cornelia Halin, Scott N. Mueller, Marc D. Beyer, Sammy Bedoui, Zeinab Abdullah, Jan Schröder, Axel Kallies","doi":"10.1038/s41590-025-02276-7","DOIUrl":"10.1038/s41590-025-02276-7","url":null,"abstract":"Exhausted CD8+ T (TEX) cell responses are maintained by precursors of exhausted T (TPEX) cells that possess high self-renewal and developmental potential. TPEX cells also drive the proliferative burst of effector T cells upon therapeutic immune checkpoint blockade (ICB). However, the spatial context and signals that regulate their differentiation and function are not well defined. Here we identify developmental and functional compartmentalization of TPEX and TEX cells across secondary lymphoid organs during chronic infection. We show that stem-like CD62L+ TPEX and effector-like CX3CR1+ TEX cells constitute a distinct developmental lineage that is promoted by the lymph node (LN) microenvironment and dependent on the transcription factor KLF2. LNs act as a niche in which migratory dendritic cells provide antigen and costimulatory signals to maintain the proliferative fitness of CD62L+ TPEX cells and generation of CX3CR1+ TEX cells. Moreover, LNs exclusively drive the proliferative burst and systemic dissemination of CX3CR1+ TEX cells during ICB. Thus, our findings identify a unique role for LNs in the maintenance of T cell differentiation and function during systemic chronic infection and ICB therapy. Here the authors show a function for lymph nodes in the maintenance of effector T cell differentiation and function during chronic infection and checkpoint blockade, identifying a spatial component in the regulation of exhausted T cell fitness.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 10","pages":"1752-1765"},"PeriodicalIF":27.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059695","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