Nature Immunology最新文献_第4页

Train your histones 训练组蛋白

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-30 DOI: 10.1038/s41590-025-02214-7

Laurie A. Dempsey

{"title":"Train your histones","authors":"Laurie A. Dempsey","doi":"10.1038/s41590-025-02214-7","DOIUrl":"https://doi.org/10.1038/s41590-025-02214-7","url":null,"abstract":"Previous cellular experiences can be remembered by epigenetic modifications of chromatin, which can then promote or impair subsequent cellular responses. This epigenetic memory process underlies the concept of ‘trained immunity’ that occurs in innate immune cells. In Cell, Ziogas et al. show that monocytes from humans vaccinated with Bacille Calmette-Guérin (BCG) undergo long-term epigenetic reprogramming that involves histone H3 lactylation on lysine 18 (H3K18la). BCG-induced training increases intracellular lactate production, in part by increasing expression of PKM, LDHA and LDHB. After BCG stimulation, the chromatin modifier p300–CBP promotes H3K18la post-translational modifications, which mainly occur at distal enhancers — in particular, at loci enriched for bZIP transcription factor motifs and CTCF-binding sites. Notably, this response seems to rely on intracellular lactate sources. This H3K18la memory response is associated with increased cytokine and chemokine gene expression that can persist for months after initial stimulation. These findings provide mechanistic underpinnings for the BCG-mediated trained immune effects.Original reference: Cell 188, 2992–3012 (2025)","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"7 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520442","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

Y do T cells fail T细胞会失败

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-30 DOI: 10.1038/s41590-025-02215-6

Nicholas J. Bernard

{"title":"Y do T cells fail","authors":"Nicholas J. Bernard","doi":"10.1038/s41590-025-02215-6","DOIUrl":"https://doi.org/10.1038/s41590-025-02215-6","url":null,"abstract":"Loss of the Y chromosome in blood cells occurs more commonly as men age and is associated with an increased risk of cancer and other inflammatory diseases. Cancer cells that lose Y chromosome expression are also considered a marker of poor outcome. Data now published in Nature link loss of tumor cell Y chromosomes with loss in immune cells that infiltrate the tumor microenvironment (TME). Using a wide variety of human tumors and a bespoke transcriptomic method to track chromosomal loss, the researchers found an association between Y chromosomal loss and worse survival outcomes with more aggressive tumor phenotypes. In addition, the degree of loss in tumor cells was predictive of the level of loss in other cell types in the TME, including immune cells and particularly in T cells. Mouse modeling indicated that loss of epithelial Y chromosomes can drive loss in these neighboring tumor-infiltrating T cells but not in blood cells. How does this work? The data seem to rule out a role for T cell exhaustion, but this is presently an open question. Nevertheless, the findings are intriguing and indicate the clinical need to assess Y chromosome stability of benign cells in the TME, with potential implications for T cell immunotherapies.Original reference: Nature https://doi.org/10.1038/s41586-025-09071-2 (2025)","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"67 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520440","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

Lipids rewire T cell exhaustion 脂质重新连接T细胞衰竭

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-27 DOI: 10.1038/s41590-025-02177-9

Marie-Elen Tuchel, Annette Oxenius

引用次数: 0

Restriction of innate Tγδ17 cell plasticity by an AP-1 regulatory axis AP-1调控轴对先天t - γδ17细胞可塑性的限制

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-27 DOI: 10.1038/s41590-025-02206-7

Morgan E. Parker, Naren U. Mehta, Tzu-Chieh Liao, William H. Tomaszewski, Stephanie A. Snyder, Julia Busch, Maria Ciofani

{"title":"Restriction of innate Tγδ17 cell plasticity by an AP-1 regulatory axis","authors":"Morgan E. Parker, Naren U. Mehta, Tzu-Chieh Liao, William H. Tomaszewski, Stephanie A. Snyder, Julia Busch, Maria Ciofani","doi":"10.1038/s41590-025-02206-7","DOIUrl":"https://doi.org/10.1038/s41590-025-02206-7","url":null,"abstract":"Interleukin-17 (IL-17)-producing γδ T (Tγδ17) cells are innate-like mediators of intestinal barrier immunity. Although IL-17-producing helper T cell and group 3 innate lymphoid cell plasticity have been extensively studied, the mechanisms governing Tγδ17 cell effector flexibility remain undefined. Here, we combined type 3 fate mapping with single-cell ATAC-sequencing/RNA-sequencing multiome profiling to define the cellular features and regulatory networks underlying Tγδ17 cell plasticity. During homeostasis, Tγδ17 cell effector identity was stable across tissues, including for intestinal T-bet+ Tγδ17 cells that restrained interferon-γ production. However, Salmonella enterica subsp. enterica serovar Typhimurium infection induced intestinal Vγ6+ Tγδ17 cell conversion into type 1 effectors, with loss of IL-17A production and partial RORγt downregulation. Multiome analysis revealed a trajectory along Vγ6+ Tγδ17 cell effector conversion, with TIM-3 marking ex-Tγδ17 cells with enhanced type 1 functionality. Last, we characterized and validated a critical AP-1 regulatory axis centered around JUNB and FOSL2 that controls Vγ6+ Tγδ17 cell plasticity by stabilizing type 3 identity and restricting type 1 effector conversion.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"7 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500409","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

Microglia loss triggers glial stress and white matter damage in human leukodystrophy 在人类脑白质营养不良中，小胶质细胞的丢失会引发胶质细胞应激和白质损伤

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-26 DOI: 10.1038/s41590-025-02194-8

引用次数: 0

Mutations in the human CSF1R gene impact microglia’s maintenance of brain white matter integrity 人CSF1R基因突变影响小胶质细胞对脑白质完整性的维持

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-26 DOI: 10.1038/s41590-025-02195-7

Siling Du, Yingyue Zhou, Dian Li, Julia Lier, Marina Cella, Mari Tada, Hideomi Hamasaki, Junjie Wu, Zhangying Cai, Jennifer L. Orthmann-Murphy, Akiyoshi Kakita, Jonathan Kipnis, Caroline G. Bergner, Marco Colonna

{"title":"Mutations in the human CSF1R gene impact microglia’s maintenance of brain white matter integrity","authors":"Siling Du, Yingyue Zhou, Dian Li, Julia Lier, Marina Cella, Mari Tada, Hideomi Hamasaki, Junjie Wu, Zhangying Cai, Jennifer L. Orthmann-Murphy, Akiyoshi Kakita, Jonathan Kipnis, Caroline G. Bergner, Marco Colonna","doi":"10.1038/s41590-025-02195-7","DOIUrl":"https://doi.org/10.1038/s41590-025-02195-7","url":null,"abstract":"Microglia, the brain’s resident macrophages, depend on interleukin-34 and colony-stimulating factor 1 (CSF1) for their development and maintenance, engaging the CSF1 receptor (CSF1R). Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a neurodegenerative disorder affecting the brain’s white matter, is caused by heterozygous pathogenic mutations in the CSF1R gene. This study investigated molecular mechanisms underlying ALSP using single-nucleus RNA sequencing on postmortem brain specimens. Results showed a significant reduction in microglia in ALSP brains, with remaining cells exhibiting a unique activation signature. This reduction correlated with decreased myelinating oligodendrocytes (OLs) and increased neuropilin-2+ OLs with a stress-response and anti-apoptotic signature, driven by STAT3 and fibroblast growth factor receptor pathways. Additionally, astrocytes displayed maladaptive activation and stress responses. These findings underscore microglia’s crucial role in supporting OL myelination and limiting astrocyte repair responses, suggesting therapeutic strategies balancing CSF1R, fibroblast growth factor receptor and STAT3 pathways for ALSP and other genetically caused microgliopathies.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"17 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488427","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

Beneficial role of GZMK+CD8+ T cells in neurodegeneration GZMK+CD8+ T细胞在神经退行性变中的有益作用

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-25 DOI: 10.1038/s41590-025-02209-4

引用次数: 0

Neuroprotective liver portal area macrophages attenuate hepatic inflammation

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-19 DOI: 10.1038/s41590-025-02190-y

Mengli Xu, Zheng Liu, Qi Pan, Zhenzhen Cai, Xinlin Li, Songlin Huang, Xinru Wang, Yilun Xu, Jiayang Liu, Yujie Zhai, Jie Yang, Borui Li, Zhan Fan, Yafang Lu, Lulu Gao, Yutong Han, Qingming Luo, Zhihong Zhang

{"title":"Neuroprotective liver portal area macrophages attenuate hepatic inflammation","authors":"Mengli Xu, Zheng Liu, Qi Pan, Zhenzhen Cai, Xinlin Li, Songlin Huang, Xinru Wang, Yilun Xu, Jiayang Liu, Yujie Zhai, Jie Yang, Borui Li, Zhan Fan, Yafang Lu, Lulu Gao, Yutong Han, Qingming Luo, Zhihong Zhang","doi":"10.1038/s41590-025-02190-y","DOIUrl":"https://doi.org/10.1038/s41590-025-02190-y","url":null,"abstract":"Tissue macrophages have an important role in the maintenance of liver homeostasis, and their functions are closely related to spatial localization. Here, through integration of whole liver lobe imaging and single-cell RNA sequencing analysis of CX3CR1+ cells in the mouse liver, we identified a dense network of CX3CR1+CD63+ liver portal area macrophages (LPAMs) that exhibited transcriptional and spatial differences compared with CX3CR1+CD207+ liver capsular macrophages. The survival of LPAMs was dependent on colony-stimulating factor 1 receptor (CSF1R). LPAMs colonized the hepatic portal area of mice after birth and were replenished from bone-marrow-derived cells during liver homeostasis. LPAMs efficiently captured antigens derived from hepatocytes and closely interacted with sympathetic nerves around the portal vein. Deletion of LPAMs led to increased neutrophil infiltration and worsened sympathetic nerve degeneration during hepatic nonalcoholic steatohepatitis. In summary, our results provide insights into a distinct subset of nerve-associated portal macrophages that function to maintain liver immune homeostasis.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"24 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319295","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

Portal macrophages maintain liver homeostasis

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-19 DOI: 10.1038/s41590-025-02184-w

Sheau Yng Lim, Hwee Ying Lim, Veronique Angeli

引用次数: 0

Peripheral infection wires T cells in the brain 外周感染会连接大脑中的T细胞

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-18 DOI: 10.1038/s41590-025-02200-z

Alexis M. Johnson, John R. Lukens

引用次数: 0