Genes and immunity最新文献_第2页

An efficient framework to decipher microRNA regulatory programs applied to T cells. 一个有效的框架来破译应用于T细胞的microRNA调控程序。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-08-18 DOI: 10.1038/s41435-025-00351-5

Hongya Zhu, Divya Ganapathi Sankaran, Norah L Smith, Ciarán W P Daly, Kristel Yee Mon, Cybelle Tabilas, Erin M Wissink, Brian D Rudd, Andrew Grimson

{"title":"An efficient framework to decipher microRNA regulatory programs applied to T cells.","authors":"Hongya Zhu, Divya Ganapathi Sankaran, Norah L Smith, Ciarán W P Daly, Kristel Yee Mon, Cybelle Tabilas, Erin M Wissink, Brian D Rudd, Andrew Grimson","doi":"10.1038/s41435-025-00351-5","DOIUrl":"10.1038/s41435-025-00351-5","url":null,"abstract":"Naïve CD8 + T cells are heterogenous, with subsets exhibiting divergent kinetics and functions post-activation. MicroRNAs, important mediators of post-transcriptional regulation, contribute to specification of different naïve T cell subsets. However, the microRNA regulatory circuits mediating functional specialization of naïve subsets are poorly understood. Here, we profiled microRNA expression in diverse subsets of naïve CD8 + T cells, revealing significant differences in their microRNA expression landscapes. We developed a novel framework, miR-Inf, to decipher microRNA regulatory programs. miR-Inf features two innovative attributes: (i) an efficient approach based on intron-exon ratios to estimate gene decay rates from a compendium of RNA-seq profiles, in order to better capture microRNA regulatory effects, and (ii) identification of cell-type-specific microRNA targets by integrating decay rate data and microRNA expression data. We applied this framework to identify consequential miRNAs in naïve CD8 + T cell subsets and predicted their subset-specific targets. Our analyses revealed that miR-29, a microRNA known to be important in CD8 + T cells, likely functions by modulating transcripts encoding epigenetic factors, thereby pre-programming different naïve T cell subsets to exhibit different immune responses post-activation. Collectively, our data and broadly applicable framework defined microRNA regulatory circuits across a variety of naïve CD8 + T cell subsets.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Neutrophil extracellular traps aggravate periodontitis by disturbing regulatory T-cell differentiation. 中性粒细胞胞外陷阱通过干扰调节性t细胞分化而加重牙周炎。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-08-11 DOI: 10.1038/s41435-025-00350-6

Beibei Chen, Danni Song, Tianfan Cheng, Lijian Jin, Yongming Li, Chongshan Liao

{"title":"Neutrophil extracellular traps aggravate periodontitis by disturbing regulatory T-cell differentiation.","authors":"Beibei Chen, Danni Song, Tianfan Cheng, Lijian Jin, Yongming Li, Chongshan Liao","doi":"10.1038/s41435-025-00350-6","DOIUrl":"10.1038/s41435-025-00350-6","url":null,"abstract":"Excessive neutrophil extracellular traps (NETs) induce an intense inflammatory response in periodontitis. Recently, Tregs were shown to be essential for attenuating inflammation-driven bone resorption. However, the regulation of Tregs differentiation by NETs in periodontitis is still unclear and needs further investigation. In this study, a murine experimental periodontitis model was established either without or with NETs depletion via DNase I. Firstly, we revealed that NETs accumulated significantly in both periodontal tissues and sera of mice models with periodontitis, while the depletion of NETs alleviated alveolar bone resorption. Moreover, RNA sequencing and bioinformatics analysis revealed that NETs depletion regulated the immune response of gingival tissue, especially affecting T-cell differentiation, and identified potential regulatory pathways. Subsequently, we verified that inhibition of NETs promoted the infiltration of Tregs and increased expression levels of IL-10 and TGF-β in periodontal tissue. Furthermore, in vitro studies demonstrated that NETs produced by P. g-LPS-stimulated neutrophils impeded the differentiation of co-cultured naive CD4+ T cells into Tregs, which could be restored by DNase I-mediated digestion of NETs. In conclusion, excessive NETs could exacerbate alveolar bone resorption in periodontitis by interfering with the differentiation of Tregs, and DNase I provides a novel targeted strategy for the immunotherapy of periodontitis.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 multi-omics approach reveals dysregulated TNF-related signaling pathways in circulating NK and T cell subsets of young children with autism. 多组学方法揭示了自闭症儿童循环NK和T细胞亚群中tnf相关信号通路失调。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-07-30 DOI: 10.1038/s41435-025-00349-z

Wared Nour-Eldine, Samia M Ltaief, Khalid Ouararhni, Nimshitha P Abdul Manaph, Alberto de la Fuente, Ilham Bensmail, Houari B Abdesselem, Abeer R Al-Shammari

{"title":"A multi-omics approach reveals dysregulated TNF-related signaling pathways in circulating NK and T cell subsets of young children with autism.","authors":"Wared Nour-Eldine, Samia M Ltaief, Khalid Ouararhni, Nimshitha P Abdul Manaph, Alberto de la Fuente, Ilham Bensmail, Houari B Abdesselem, Abeer R Al-Shammari","doi":"10.1038/s41435-025-00349-z","DOIUrl":"10.1038/s41435-025-00349-z","url":null,"abstract":"Peripheral immune dysregulation is frequently reported in autism spectrum disorder (ASD); however, the underlying molecular mechanisms remain unclear. We recruited a well-defined cohort of young Arab children with ASD, aged 2-4 years, along with matched controls in Qatar. Using a multimodal approach, we integrated transcriptomic, proteomic, and single-cell RNA-seq data analyses from this cohort. Targeted transcriptomic profiling identified differential expression of 50 immune-related genes in the circulating PBMCs of children with ASD, three of which (JAK3, CUL2, and CARD11) negatively correlated with ASD symptom severity. These gene signatures were validated in independent studies using blood and brain tissues from individuals with ASD. Enrichment analysis revealed involvement of these genes in immune function, particularly through TNF signaling pathway. Proteomic analysis highlighted disrupted TNF signaling and upregulated levels of TNFSF10 (TRAIL), TNFSF11 (RANKL), and TNFSF12 (TWEAK) in plasma of individuals with ASD. Single-cell RNA-seq revealed that B cells, CD4 T cells, and NK cells potentially contributed to these upregulations in ASD. Dysregulated TRAIL, RANKL, and TWEAK signaling pathways were specifically observed in CD8 T cells, CD4 T cells, and NK cells of individuals with ASD. These findings provide new insights into immune dysregulation mechanisms in ASD and highlight potential therapeutic targets.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Impact of tertiary lymphoid structure scores and their stage of maturation on prognosis of colorectal cancer patients. 三级淋巴样结构评分及其成熟阶段对结直肠癌患者预后的影响。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-07-28 DOI: 10.1038/s41435-025-00346-2

Si Shen, Ran Sun, Tian Wang, Danfang Zhang, Na Che, Xiao Wang, Nan Zhao

{"title":"Impact of tertiary lymphoid structure scores and their stage of maturation on prognosis of colorectal cancer patients.","authors":"Si Shen, Ran Sun, Tian Wang, Danfang Zhang, Na Che, Xiao Wang, Nan Zhao","doi":"10.1038/s41435-025-00346-2","DOIUrl":"10.1038/s41435-025-00346-2","url":null,"abstract":"Tertiary lymphoid structures (TLSs) are essential for promoting immune responses against tumours. However, the impact of TLS score and its maturation stage on the prognosis of colorectal cancer (CRC) patients has not yet been clarified. The aim of this study was to investigate the relationship between TLS score and its maturation stage and CRC prognosis through a retrospective study. In this study, firstly, high TLS score (≥0.752) was found to be a favourable prognostic factor for the survival of CRC patients using the TCGA database (HR = 0.381, 95% CI = 0.222 ~ 0.656). Secondly, CCL19, CCL21, and CXCL13 were found to be differential genes in the high and low TLS score groups in combination with several databases, and their main function was to chemotaxis TLS maturation. Subsequently, immunohistochemical staining was used to clarify the stage of TLS maturation in 76 clinical samples and to investigate its impact on patients' survival prognosis. Finally, the validation of TNFRSF17 gene function was completed by cellular experiments. Analysis of the clinical samples showed that patients with higher early TLS (E-TLS) density had shorter survival than those with lower density (P = 0.016). High E-TLS density may be an independent risk factor for CRC (HR = 6.40, 95% CI = 1.82 ~ 22.55). However, the density of secondary follicular-like TLS did not show a significant prognostic effect in this study. In conclusion, patients with high TLS scores had longer survival, higher expression of immune checkpoint genes, and higher expression of TNFRSF17, which promotes T-cell infiltration and adhesion, but highly aggregated E-TLS may hamper patients' survival prognosis.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

N6-methyladenosine RNA modification regulates microglial phagocytosis in the APP/PS1 mouse model of Alzheimer's disease. n6 -甲基腺苷RNA修饰调控阿尔茨海默病APP/PS1小鼠模型的小胶质细胞吞噬

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-07-24 DOI: 10.1038/s41435-025-00347-1

Xueqi Qu, Li Lin, Yinhu Li, Yuewen Chen, Yu Chen

{"title":"N6-methyladenosine RNA modification regulates microglial phagocytosis in the APP/PS1 mouse model of Alzheimer's disease.","authors":"Xueqi Qu, Li Lin, Yinhu Li, Yuewen Chen, Yu Chen","doi":"10.1038/s41435-025-00347-1","DOIUrl":"10.1038/s41435-025-00347-1","url":null,"abstract":"N6-methyladenosine (m6A) methylation and abnormal cellular processes are involved in neurodegenerative diseases, including Alzheimer's disease (AD). However, the functions of molecular signatures associated with m6A modification in AD remain unclear. Here, we show that m6A abundance is elevated in the hippocampus in 6-month-old APP/PS1 mice, an AD mouse model. Comparative analysis of mRNA m6A modification profiles revealed substantial variation in m6A modifications between AD and control mice. Transcripts with differential m6A modification (either hyper- or hypomethylation) were enriched in the regulation of cellular processes, including metabolic alterations, immune responses, synaptic transmission, and responses to stimuli, in both the nervous and immune systems. Moreover, the m6A-associated immune features were involved in microglial signatures, including cytokine signaling, microglial homeostasis, and microglial phagocytosis. Importantly, we identified genes with significant enrichment of m6A modifications in AD mice. Among these, we confirmed that m6A methylation was associated with the gene expression levels of CD9 and Cebpβ. Moreover, these alterations were negatively associated with microglia-mediated phagocytosis in vitro, which in turn impaired activated microglia-induced inflammation. Taken together, these findings suggest that the alteration of m6A modification contributes to the progression of AD by regulating gene expression and microglial function.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Genetic insights into the association between inflammatory bowel disease and Alzheimer's disease. 对炎症性肠病和阿尔茨海默病之间关系的遗传见解。

IF 5 3区医学

Genes and immunity Pub Date : 2025-07-16 DOI: 10.1038/s41435-025-00344-4

Lu Zeng, Charles C White, David A Bennett, Hans-Ulrich Klein, Philip L De Jager

{"title":"Genetic insights into the association between inflammatory bowel disease and Alzheimer's disease.","authors":"Lu Zeng, Charles C White, David A Bennett, Hans-Ulrich Klein, Philip L De Jager","doi":"10.1038/s41435-025-00344-4","DOIUrl":"10.1038/s41435-025-00344-4","url":null,"abstract":"Myeloid cells, including monocytes, macrophages, and microglia, play major roles in innate and adaptive immune responses. Alzheimer's disease (AD) and inflammatory bowel disease (IBD) susceptibility loci are both enriched for genes expressed in myeloid cells, so we assessed whether these myeloid pathways may be shared. Leveraging genome-wide association study results, we investigated the causal effect of IBD (including ulcerative colitis and Crohn's disease) variants on AD and its endophenotypes. Microglia and monocyte expression Quantitative Trait Locus (eQTLs) were used to examine the functional consequences of IBD and AD variants. Our results revealed that the sets of genes and pathways implicated in AD and IBD susceptibility are largely distinct. Specifically, AD loci were enriched for microglial eQTLs, while IBD loci were enriched for monocyte eQTLs. Nonetheless, genetically determined IBD was associated with a modest protective effect against AD (p < 0.03), whereas CD susceptibility was linked to a modest increase in amyloid accumulation (β = 7.14, p = 0.02) and AD risk. UC susceptibility, on the other hand, was associated with increased TDP-43 deposition (β = 7.58, p value = 6.11 × 10-4). Thus, the relationship between gastrointestinal inflammatory diseases and AD is complex, but there is evidence for a modest role of IBD susceptibility on AD risk that could yield valuable therapeutic insights.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Peripheral immune imbalance in pediatric fulminant myocarditis revealed by single-cell sequencing and plasma proteomics 单细胞测序和血浆蛋白质组学揭示小儿暴发性心肌炎的外周免疫失衡。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-07-08 DOI: 10.1038/s41435-025-00343-5

Keyu Liu, Li Zhang, Xiuyun Duan, Hailin Jia, Shan Zhou, Mengjie Ma, Xiao Pan, Xiaojing Zhang, Bo Han

{"title":"Peripheral immune imbalance in pediatric fulminant myocarditis revealed by single-cell sequencing and plasma proteomics","authors":"Keyu Liu, Li Zhang, Xiuyun Duan, Hailin Jia, Shan Zhou, Mengjie Ma, Xiao Pan, Xiaojing Zhang, Bo Han","doi":"10.1038/s41435-025-00343-5","DOIUrl":"10.1038/s41435-025-00343-5","url":null,"abstract":"The precise pathological immune subsets and molecular changes in myocarditis, especially fulminant myocarditis (FM), have not been elucidated. We present a systemic analysis of immunological signatures and cell communications from pediatric PBMCs during the acute and recovery phases of FM using scRNA-seq. The peripheral immune profile in acute FM exhibited significant dysregulation in the proportion and function of immune cells. Several unique cell types, regulatory B cells, MAIT cells, adaptive NK cells, and CD8+Tpex cells, were identified in peripheral blood. Transcriptomic analysis revealed elevated expression of chemokine receptor CXCR4 and S100A family genes across nearly all cell types in the FM acute phase, as well as MHC-II molecules in antigen-presenting cells. TCR and BCR analysis showed remarkable clonal amplification and skewed V gene usage. Ligand receptor analysis highlighted active communication between myeloid cells and other immune cells. Furthermore, plasma proteomics analysis identified 36 differentially expressed proteins that interact with peripheral immune cells. Notably, anti-inflammation factors IL-10 and TGFB1 demonstrated significant potential in regulating the activity of downstream target genes involved in the immune response of peripheral immune cells. These findings enhance the understanding of the immune landscape of pediatric FM and provide valuable insights for developing potential diagnostic and therapeutic strategies.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 4","pages":"394-412"},"PeriodicalIF":4.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Regulation of CD4 + T cell differentiation and function by glucose metabolism 糖代谢对CD4 + T细胞分化和功能的调节。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-07-05 DOI: 10.1038/s41435-025-00340-8

Yubo Liu, Yiwen Zhou, Ji Zhang, Jingyi Li, Liyun Zou

{"title":"Regulation of CD4 + T cell differentiation and function by glucose metabolism","authors":"Yubo Liu, Yiwen Zhou, Ji Zhang, Jingyi Li, Liyun Zou","doi":"10.1038/s41435-025-00340-8","DOIUrl":"10.1038/s41435-025-00340-8","url":null,"abstract":"The long-term persistence of naive T lymphocytes is maintained by a state of relative quiescence. Upon antigenic stimulation, these naive T cells undergo rapid activation and proliferation, differentiating into effector cells with specific clonal expansion. Recently, in-depth studies have revealed a fundamental difference in the metabolic requirements of distinct T cell subsets. The fate of CD4 + T cells is influenced by glucose-mediated glycolysis and oxidative phosphorylation (OXPHOS). In this context, key enzymes and various glycolytic intermediates, in conjunction with transcription factors and cytokines, play a crucial role in CD4 + T cell differentiation and function. In our study, we investigated the mechanisms underlying glycolytic reprogramming in CD4 + T cells, with a particular focus on the role of glycolytic enzymes in modulating cytokines and transcription factors that govern T cell differentiation.Our aim is to provide novel insights into the treatment of clinically relevant immune diseases by thoroughly elucidating the characteristics and potential regulatory mechanisms of glucose metabolism in CD4 + T cells.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 4","pages":"287-296"},"PeriodicalIF":4.5,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Folate metabolism-associated CYP26A1 is a clinico-immune target in colorectal cancer 叶酸代谢相关的CYP26A1是结直肠癌的临床免疫靶点。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-07-03 DOI: 10.1038/s41435-025-00342-6

Yifei Zhu, Teng Zhou, Yao Zheng, Yanxi Yao, Mingxi Lin, Cheng Zeng, Yuxin Yan, Yifei Zhou, Dou-Dou Li, Jian Zhang

{"title":"Folate metabolism-associated CYP26A1 is a clinico-immune target in colorectal cancer","authors":"Yifei Zhu, Teng Zhou, Yao Zheng, Yanxi Yao, Mingxi Lin, Cheng Zeng, Yuxin Yan, Yifei Zhou, Dou-Dou Li, Jian Zhang","doi":"10.1038/s41435-025-00342-6","DOIUrl":"10.1038/s41435-025-00342-6","url":null,"abstract":"Folic acid plays a crucial role in cellular regulation and metabolism, commonly included in dietary supplements. Despite this, its involvement in colorectal cancer (CRC), particularly in metabolic pathways and immune evasion, remains poorly understood. We developed the FMRG_score system using machine learning algorithms on TCGA and GEO data to assess modification patterns influencing clinical outcomes and immune characteristics in CRC. The system’s reliability was validated across multiple external immunotherapy cohorts. We examined associations between FMRG-related features and clinical traits, mutation profiles, biological functions, immune infiltration, therapy responses, and drug sensitivities. By integrating in vitro and in vivo experiments with bioinformatics, we built a nine-gene risk model linked to folate metabolism for CRC prognosis. Notably, CYP26A1, a key gene in the model, was upregulated in CRC tissues, promoting cell proliferation, migration, invasion, and contributing to an immunosuppressive tumor microenvironment. Significant differences in clinical traits, immune infiltration, checkpoint expression, therapy response, and drug sensitivity were observed between risk groups. This folate-based scoring system provides a novel tool for evaluating CRC prognosis, tumor microenvironment, and response to immunotherapy. We also propose CYP26A1 as a potential oncogene in CRC, offering new therapeutic insights.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 4","pages":"376-393"},"PeriodicalIF":4.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

S-nitrosylated NEDD4 exacerbates gouty arthritis by upregulating NOD1 to induce pyroptosis s -亚硝基化的NEDD4通过上调NOD1诱导焦亡而加重痛风性关节炎。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-07-01 DOI: 10.1038/s41435-025-00341-7

Xiusheng Qu, Qingdong Wang, Hongbin Qiu

{"title":"S-nitrosylated NEDD4 exacerbates gouty arthritis by upregulating NOD1 to induce pyroptosis","authors":"Xiusheng Qu, Qingdong Wang, Hongbin Qiu","doi":"10.1038/s41435-025-00341-7","DOIUrl":"10.1038/s41435-025-00341-7","url":null,"abstract":"Gouty arthritis (GA) is a common inflammatory disease which has no effective treatments. Pyroptosis has been reported to exacerbate the progression of GA. We aimed to explore the molecular mechanism by which S-nitrosylated NEDD4 accelerates GA progression by regulating pyroptosis. In our study, we found NOD1 knockdown inhibited pyroptosis and reduced c-Caspase-1, NLRP3, ASC, and GSDMD-N expression, IL-1β and IL-18 levels, and XOD activity in GA in vivo and in vitro. In addition, NOD1 knockdown alleviated inflammatory symptoms of joint tissues in GA mice model. Moreover, downregulation of NEDD4 caused by S-nitrosylation modification at C365 site upregulated NOD1 expression by reducing ubiquitination and degradation of NOD1. Furthermore, iNOS promoted NOD1 expression by mediating S-nitrosylation of NEDD4 thereby inducing GA in vitro. In conclusion, S-nitrosylation of NEDD4 promoted NLRP3-mediated pyroptosis by upregulating NOD1 expression, which ultimately accelerated the development of GA. We are the first to report the expression patterns of NEDD4 and NOD1 in GA, and demonstrated firstly that S-nitrosylation of NEDD4 inhibited ubiquitination-mediated degradation of NOD1, thereby modulating pyroptosis in GA. By elucidating how S-nitrosylation of NEDD4 orchestrates NOD1-mediated pyroptosis, this work opens avenues for developing first-in-class therapies for GA.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 4","pages":"365-375"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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