Nature Immunology最新文献

A co-stimulatory signal via the coinhibitory TIGIT. 一个通过共抑制TIGIT的共刺激信号。

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-10-24 DOI: 10.1038/s41590-025-02315-3

Kazuko Shibuya,Akira Shibuya

引用次数: 0

Microglial MEF2C is a uniquely human bridge between neurodevelopment and neurodegeneration. 小胶质细胞MEF2C是人类神经发育和神经变性之间的独特桥梁。

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-10-22 DOI: 10.1038/s41590-025-02313-5

Ryan J Rahman,Mariko L Bennett

引用次数: 0

Transcriptional and epigenetic targets of MEF2C in human microglia contribute to cellular functions related to autism risk and age-related disease. MEF2C在人小胶质细胞中的转录和表观遗传靶点参与与自闭症风险和年龄相关疾病相关的细胞功能。

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-10-22 DOI: 10.1038/s41590-025-02299-0

Celina Nguyen,Emily H Broersma,Anna S Warden,Cristina Mora,Claudia Z Han,Zahara Keulen,Nathanael Spann,Jing Wang,Gabriela Ramirez,Samantha Mak,Samantha Trescott,Mohammadparsa Khakpour,Avalon Johnson,Fatir Qureshi,Michael R La Frano,Kiana Mohajeri,Michael E Talkowski,Olivia Corradin,Marie-Ève Tremblay,Christopher K Glass,Nicole G Coufal

{"title":"Transcriptional and epigenetic targets of MEF2C in human microglia contribute to cellular functions related to autism risk and age-related disease.","authors":"Celina Nguyen,Emily H Broersma,Anna S Warden,Cristina Mora,Claudia Z Han,Zahara Keulen,Nathanael Spann,Jing Wang,Gabriela Ramirez,Samantha Mak,Samantha Trescott,Mohammadparsa Khakpour,Avalon Johnson,Fatir Qureshi,Michael R La Frano,Kiana Mohajeri,Michael E Talkowski,Olivia Corradin,Marie-Ève Tremblay,Christopher K Glass,Nicole G Coufal","doi":"10.1038/s41590-025-02299-0","DOIUrl":"https://doi.org/10.1038/s41590-025-02299-0","url":null,"abstract":"MEF2C encodes a transcription factor that is critical in nervous system development. Here, to examine disease-associated functions of MEF2C in human microglia, we profiled microglia differentiated from isogenic MEF2C-haploinsufficient and MEF2C-knockout induced pluripotent stem cell lines. Complementary transcriptomic and functional analyses revealed that loss of MEF2C led to a hyperinflammatory phenotype with broad phagocytic impairment, lipid accumulation, lysosomal dysfunction and elevated basal inflammatory cytokine secretion. Genome-wide profiling of MEF2C-bound sites coupled with the active regulatory landscape enabled inference of its transcriptional functions and potential mechanisms for MEF2C-associated cellular functions. Transcriptomic and epigenetic approaches identified substantial overlap with idiopathic autism datasets, suggesting a broader role of human microglial MEF2C dysregulation in idiopathic autism. In a mouse xenotransplantation model, loss of MEF2C led to morphological, lysosomal and lipid abnormalities in human microglia in vivo. Together, these studies reveal mechanisms by which reduced microglial MEF2C could contribute to the development of neurological diseases.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"101 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339028","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 unified multimodal single-cell framework reveals a discrete state model of hematopoiesis in mice. 统一的多模态单细胞框架揭示了小鼠造血的离散状态模型。

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-10-22 DOI: 10.1038/s41590-025-02307-3

Kyle Ferchen,Xuan Zhang,Kairavee Thakkar,Guangyuan Li,David Bernardicius,Sidharth Sen,Priyanka Rawat,Andre Olsson,Sierra N Bennett,Crystal Potter,Fred D Finkelman,Josh Croteau,Samantha Morris,Harinder Singh,Nathan Salomonis,H Leighton Grimes

{"title":"A unified multimodal single-cell framework reveals a discrete state model of hematopoiesis in mice.","authors":"Kyle Ferchen,Xuan Zhang,Kairavee Thakkar,Guangyuan Li,David Bernardicius,Sidharth Sen,Priyanka Rawat,Andre Olsson,Sierra N Bennett,Crystal Potter,Fred D Finkelman,Josh Croteau,Samantha Morris,Harinder Singh,Nathan Salomonis,H Leighton Grimes","doi":"10.1038/s41590-025-02307-3","DOIUrl":"https://doi.org/10.1038/s41590-025-02307-3","url":null,"abstract":"Large-scale, unbiased single-cell genomics studies of complex developmental compartments, such as hematopoiesis, have inferred novel cell states and trajectories; however, further characterization has been hampered by difficulty isolating cells corresponding to discrete genomic states. To address this, we present a framework that integrates multimodal single-cell analyses (RNA, surface protein and chromatin) with high-dimensional flow cytometry and enables semiautomated enrichment and functional characterization of diverse cell states. Our approach combines transcription factor expression with chromatin activity to uncover hierarchical gene regulatory networks driving these states. We delineated and isolated rare bone marrow Lin-Sca-CD117+CD27+ multilineage cell states ('MultiLin'), validated predicted lineage trajectories and mapped differentiation potentials. Additionally, we used transcription factor activity on chromatin to trace and isolate multilineage progenitors undergoing multipotent to oligopotent lineage restriction. In the proposed model of steady-state hematopoiesis, discrete states governed developmental trajectories. This framework provides a scalable solution for isolating and characterizing novel cell states across different biological systems.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339027","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

Single-cell RNA profiling of blood CD4+ T cells identifies distinct helper and dysfunctional regulatory clusters in children with SLE. 单细胞RNA分析血液CD4+ T细胞识别不同的辅助和功能失调的调节簇SLE儿童。

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-10-21 DOI: 10.1038/s41590-025-02297-2

Preetha Balasubramanian,Uthra Balaji,Marina Silva Santos,Jeanine Baisch,Cynthia Smitherman,Lynnette Walters,Paola Sparagana,Lorien Nassi,Katie Stewart,Julie Fuller,Terry Means,Virginia Savova,Jacques F Banchereau,Tracey Wright,Virginia Pascual,Jinghua Gu,Simone Caielli

{"title":"Single-cell RNA profiling of blood CD4+ T cells identifies distinct helper and dysfunctional regulatory clusters in children with SLE.","authors":"Preetha Balasubramanian,Uthra Balaji,Marina Silva Santos,Jeanine Baisch,Cynthia Smitherman,Lynnette Walters,Paola Sparagana,Lorien Nassi,Katie Stewart,Julie Fuller,Terry Means,Virginia Savova,Jacques F Banchereau,Tracey Wright,Virginia Pascual,Jinghua Gu,Simone Caielli","doi":"10.1038/s41590-025-02297-2","DOIUrl":"https://doi.org/10.1038/s41590-025-02297-2","url":null,"abstract":"To characterize the complexity of the CD4⁺ T cell compartment in patients with systemic lupus erythematosus (SLE), we performed single-cell RNA sequencing of sorted blood CD4⁺ T cells from pediatric patients and healthy donors. We identified naive, memory, regulatory T (Treg) cell, proliferative and interferon-stimulated gene-high (ISG-high) clusters. Within the memory compartment, both follicular and peripheral helper cells were expanded in patients with lupus nephritis and/or high disease activity. Cytotoxic signatures were enriched in effector memory T cells re-expressing CD45RA (TEMRA), as well as in two memory subclusters, one of which overlapped with T helper 10-like cells (TH10). Notably, we observed an expansion of dysfunctional Treg cells in patients with lupus nephritis, along with upregulation of TLR5 and FCRL3 in SLE-naive Treg cells, suggesting a potential link with mucosal microbial dysbiosis. These findings highlight distinct CD4⁺ T cell subsets that may contribute to aberrant antibody responses and impaired immune regulation in SLE.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"58 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338604","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

Charting new territory for T cells in pediatric lupus. 绘制儿童狼疮中T细胞的新领域。

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-10-21 DOI: 10.1038/s41590-025-02312-6

Nan Shen,Betty P Tsao

引用次数: 0

Unexpected redundancy or harmfulness of plasmacytoid dendritic cells in viral infections. 病毒感染中浆细胞样树突状细胞的意外冗余或危害。

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-10-20 DOI: 10.1038/s41590-025-02322-4

引用次数: 0

Antigen-presenting cells as arbiters of mucosal tolerance and immunity. 抗原呈递细胞作为粘膜耐受和免疫的仲裁者。

IF 30.5 1区医学