Genes and immunity最新文献_第4页

Integrated analysis reveals NLRC4 as a potential biomarker in sepsis pathogenesis 综合分析揭示 NLRC4 是败血症发病机制中的潜在生物标记。

IF 5 3区医学

Genes and immunity Pub Date : 2024-08-24 DOI: 10.1038/s41435-024-00293-4

Chunhui Jiang, Jiani Chen, Jiaqing Xu, Chen Chen, Hongguo Zhu, Yinghe Xu, Hui Zhao, Jiaxi Chen

{"title":"Integrated analysis reveals NLRC4 as a potential biomarker in sepsis pathogenesis","authors":"Chunhui Jiang, Jiani Chen, Jiaqing Xu, Chen Chen, Hongguo Zhu, Yinghe Xu, Hui Zhao, Jiaxi Chen","doi":"10.1038/s41435-024-00293-4","DOIUrl":"10.1038/s41435-024-00293-4","url":null,"abstract":"Sepsis remains a significant global health burden and contributor to mortality, yet the precise molecular mechanisms underlying the immune response are not fully elucidated. To gain insight into this issue, we performed a comprehensive analysis using a variety of techniques including bulk RNA sequencing, single-cell RNA sequencing, and enzyme-linked immunosorbent assay (ELISA). We performed enrichment analysis of differentially expressed genes in sepsis and healthy individuals by utilizing Gene Ontology (GO) analysis and indicated significant enrichment of immune-related response. Following Weighted Gene Co-Expression Network Analysis (WGCNA) and protein-protein interaction analysis (PPI) were used to identify key immune-related hub genes and validated by ELISA to show that NLRC4 is highly expressed in sepsis. Additionally, an analysis of scRNA-seq data from newly diagnosed sepsis, sepsis diagnosis at 6 hours, and healthy samples demonstrates a significant increase in both the expression levels and proportions of NLRC4 in sepsis monocytes and neutrophils. In addition, using pySCENIC we identified upstream transcription factors that regulate NLRC4. Our study provides valuable insights into the identification of NLRC4 in peripheral blood as a potential candidate gene for the diagnosis and treatment of sepsis.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 5","pages":"397-408"},"PeriodicalIF":5.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055382","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

Deciphering the role of oxidative stress genes in idiopathic pulmonary fibrosis: a multi-omics mendelian randomization approach 解密氧化应激基因在特发性肺纤维化中的作用：一种多组学孟德尔随机方法。

IF 5 3区医学

Genes and immunity Pub Date : 2024-08-22 DOI: 10.1038/s41435-024-00292-5

Xin Liu, Dengfeng Zhang, Fangchao Zhao, Shujun Li, Haiyong Zhu, Xu Zhang

{"title":"Deciphering the role of oxidative stress genes in idiopathic pulmonary fibrosis: a multi-omics mendelian randomization approach","authors":"Xin Liu, Dengfeng Zhang, Fangchao Zhao, Shujun Li, Haiyong Zhu, Xu Zhang","doi":"10.1038/s41435-024-00292-5","DOIUrl":"10.1038/s41435-024-00292-5","url":null,"abstract":"Oxidative stress (OS) is crucial in idiopathic pulmonary fibrosis (IPF) pathogenesis, with its genes potentially acting as both causes and consequences of the disease. We identified OS-related genes from GeneCards and performed a meta-analysis on pulmonary transcriptome datasets to discover differentially expressed genes (DEGs) related to OS in IPF. We integrated this data with the largest available IPF GWAS summaries, expression quantitative trait loci (eQTLs), and DNA methylation QTLs (mQTLs) from blood. This approach aimed to identify blood OS genes and regulatory elements linked to IPF risk, incorporating the latest pulmonary eQTLs and bronchoalveolar lavage fluid microbial QTLs (bmQTLs) for a comprehensive view of gene-lung microbiota interactions through SMR and colocalization analyses. Sensitivity analyses were conducted using two additional mendelian randomization (MR) methods. Meta-analysis revealed 1090 differentially expressed OS genes between IPF patients and controls. Integration with IPF GWAS, eQTL, and mQTL data identified key genes and regulatory elements involved in IPF pathogenesis, highlighting the role of specific genes such as KCNMA1 and SLC22A5 in modulating IPF risk through epigenetic mechanisms. Colocalization analysis further identified potential interactions between gene expression and lung microbiota. Our findings elucidate the complex interplay between OS genes and IPF, suggesting potential therapeutic targets and highlighting the importance of considering epigenetic and microbial interactions in the disease’s etiology and progression.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 5","pages":"389-396"},"PeriodicalIF":5.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035688","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

Innate immune dynamics in the context of multisite EGFR mutations in lung adenocarcinoma 肺腺癌多位点表皮生长因子受体突变背景下的先天免疫动态。

IF 5 3区医学

Genes and immunity Pub Date : 2024-08-06 DOI: 10.1038/s41435-024-00288-1

Yuan Peng, Chuan Zeng, Rongxin Liao, Lu Shen, Yan Zhou, Zhenzhou Yang

{"title":"Innate immune dynamics in the context of multisite EGFR mutations in lung adenocarcinoma","authors":"Yuan Peng, Chuan Zeng, Rongxin Liao, Lu Shen, Yan Zhou, Zhenzhou Yang","doi":"10.1038/s41435-024-00288-1","DOIUrl":"10.1038/s41435-024-00288-1","url":null,"abstract":"Based on favorable outcomes and decreased propensity for lymph node and distant metastasis, multiple ground-glass nodules (GGNs) are now predominantly recognized as early-stage primary independent lung cancer. In this study, we discuss a case involving a patient with reoperative multifocal GGNs who was ultimately diagnosed with early multiple intrapulmonary metastases and multifocal primary lung cancers. This patient exhibited multisite epidermal growth factor receptor (EGFR) mutations, including the classical L858R, exon 19 deletion and the rare V834L variant. Despite a high tumor burden and the presence of various EGFR driver mutations, the patient experienced prolonged dormancy and exceptionally slow lesion growth, even without any systemic treatment. Our research indicates that the patient’s immune response against the tumor remained robust throughout the disease course. Furthermore, we found that pathways associated with integrin-mediated cell extracellular matrix adhesion played a role in activating her innate immune responses and regulating tumor dormancy. Our findings suggest that the interplay between cancer cell mutations and the tumor microenvironment (TME) phenotype during tumor evolution contributed to this patient’s prolonged survival. Integrating these aspects for lung tumor stratification is expected to improve predictions of growth potential and aid in clinical decision making.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 1","pages":"64-69"},"PeriodicalIF":5.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897257","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

Apolipoprotein E deficiency leads to the polarization of splenic macrophages towards M1 phenotype by increasing iron content 载脂蛋白 E 缺乏会通过增加铁含量导致脾巨噬细胞向 M1 表型极化。

IF 5 3区医学

Genes and immunity Pub Date : 2024-08-05 DOI: 10.1038/s41435-024-00290-7

Meng-Qi Shen, Qian Guo, Wei Li, Zhong-Ming Qian

{"title":"Apolipoprotein E deficiency leads to the polarization of splenic macrophages towards M1 phenotype by increasing iron content","authors":"Meng-Qi Shen, Qian Guo, Wei Li, Zhong-Ming Qian","doi":"10.1038/s41435-024-00290-7","DOIUrl":"10.1038/s41435-024-00290-7","url":null,"abstract":"Apolipoprotein E (ApoE) plays a crucial role in iron homeostasis in the body, while macrophages are the principal cells responsible for handling iron in mammals. However, it is unknown whether ApoE can affect the functional subtypes and the iron handling capacity of splenic macrophages (SM). Here, we investigated the effects of ApoE deficiency (ApoE−/−) on the polarization and iron content of SM and its potential mechanisms. ApoE−/− was found to induce a significant increase in the expressions of M1 marker genes CD86, IL-1β, IL-6, IL-12, TNF-α and iNOS and a reduction in M2 marker genes CD206, Arg-1, IL-10 and Ym-1 in SM of mice aged 28 weeks, Meanwhile, ApoE−/− caused a significant increase in iron content and expression of ferritin, transferrin receptor 1 (TfR1), iron regulatory protein 1 (IRP1) and heme oxygenase-1 (HO-1) and a reduction in ferroportin1 (Fpn1) in spleen and/or SM of mice aged 28 weeks. It was concluded that ApoE−/− can increase iron content through increased iron uptake mediated by TfR/ IRPs and decreased iron release mediated by Fpn1, leading to polarization of the SM to M1 phenotype.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 5","pages":"381-388"},"PeriodicalIF":5.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893251","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

Machine-learning and scRNA-Seq-based diagnostic and prognostic models illustrating survival and therapy response of lung adenocarcinoma 基于机器学习和 scRNA-Seq 的诊断和预后模型，说明肺腺癌的存活率和治疗反应。

IF 5 3区医学

Genes and immunity Pub Date : 2024-07-29 DOI: 10.1038/s41435-024-00289-0

Qingyu Cheng, Weidong Zhao, Xiaoyuan Song, Tengchuan Jin

{"title":"Machine-learning and scRNA-Seq-based diagnostic and prognostic models illustrating survival and therapy response of lung adenocarcinoma","authors":"Qingyu Cheng, Weidong Zhao, Xiaoyuan Song, Tengchuan Jin","doi":"10.1038/s41435-024-00289-0","DOIUrl":"10.1038/s41435-024-00289-0","url":null,"abstract":"Lung cancer is a major cause accounting for cancer-related mortalities, with lung adenocarcinoma (LUAD) being the most prevalent subtype. Given the high clinical and cellular heterogeneities of LUAD, accurate diagnosis and prognosis are crucial to avoid overdiagnosis and overtreatment. Taking full advantage of scRNA-Seq data to resolve the tumor heterogeneities, we explored the overall landscape of LUAD microenvironment. Utilizing the stage-specific tumor cell markers, we have developed highly accurate diagnostic and prognostic models with elevated sensitivity and specificity. The diagnostic model, developed through random forest algorithms with a thirteen-gene signature, achieved an accuracy of 96.4% and an AUC of 0.993. These metrics were further demonstrated by benchmarking with available models and scoring systems in independent cohorts. Concurrently, the prognostic model, formulated via Cox regression with a six-gene signature, effectively predicted overall survival, with elevated risk scores associated with increased fractions of cancer-associated fibroblasts, and higher likelihood of immune escape and T-cell exclusion. Subsequently, two nomograms were developed to predict survival and drug responses, facilitating their integration into clinical practice. Overall, this study underscores the potential of our models for efficient, rapid, and cost-effective diagnosis and prognosis of LUAD, adaptable to multiple expression profiling platforms and quantification methods.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 5","pages":"356-366"},"PeriodicalIF":5.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792302","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

Identification of the ferroptosis‐related gene signature and the associated regulation axis in lung cancer and rheumatoid arthritis 确定肺癌和类风湿性关节炎中的铁蛋白沉积相关基因特征及相关调控轴。

IF 5 3区医学

Genes and immunity Pub Date : 2024-07-29 DOI: 10.1038/s41435-024-00287-2

Bo Cai, Yibin Huang, Dandan Liu, Yizheng You, Nuoshi Chen, Ligang Jie, Hongyan Du

{"title":"Identification of the ferroptosis‐related gene signature and the associated regulation axis in lung cancer and rheumatoid arthritis","authors":"Bo Cai, Yibin Huang, Dandan Liu, Yizheng You, Nuoshi Chen, Ligang Jie, Hongyan Du","doi":"10.1038/s41435-024-00287-2","DOIUrl":"10.1038/s41435-024-00287-2","url":null,"abstract":"Patients with Rheumatoid arthritis (RA) have an elevated risk of lung cancer compared to the healthy population. However, there are few studies on the relationship between RA and lung adenocarcinoma (LUAD), especially the mechanisms at the genetic level. In this study, we investigated the link between RA and LUAD regarding Ferroptosis-Related Genes. The RNA-seq data of RA (GSE77298 and GSE 82107) and LUAD(GSE75037) in the Gene Expression Omnibus (GEO) database were obtained. 259 ferroptosis-related genes were obtained from the website ( http://www.zhounan.org/ferrdb/ ).The differential genes obtained from the RA and LUAD datasets were intersected with ferroptosis-related genes to obtain the ferroptosis-related differentially expressed genes (FRDEGs). Next, the mRNA-miRNA network was constructed, then Gene Set Enrichment Analysis (GSEA) for target genes were performed. The CIBERSORT algorithm was used to analyze the immune infiltration. Finally, the results were validated using external datasets (GSE89408 and GSE48780) and The Cancer Genome Atlas (TCGA) dataset. We obtained FRDEGs common to LUAD and RA: FANCD2, HELLS, RRM2, G6PD, VLDLR. These five genes play important roles in the progression of RA and LUAD. They also hold great diagnostic value for both diseases. Also, we found that LUAD and RA share common signaling pathways and similar immune mechanisms.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 5","pages":"367-380"},"PeriodicalIF":5.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855280","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

The shared role of neutrophils in ankylosing spondylitis and ulcerative colitis 中性粒细胞在强直性脊柱炎和溃疡性结肠炎中的共同作用。

IF 5 3区医学

Genes and immunity Pub Date : 2024-07-25 DOI: 10.1038/s41435-024-00286-3

Tianyou Chen, Weiming Tan, Xinli Zhan, Chenxing Zhou, Jichong Zhu, Shaofeng Wu, Boli Qin, Rongqing He, Xiaopeng Qin, Wendi Wei, Chengqian Huang, Bin Zhang, Sitan Feng, Chong Liu

{"title":"The shared role of neutrophils in ankylosing spondylitis and ulcerative colitis","authors":"Tianyou Chen, Weiming Tan, Xinli Zhan, Chenxing Zhou, Jichong Zhu, Shaofeng Wu, Boli Qin, Rongqing He, Xiaopeng Qin, Wendi Wei, Chengqian Huang, Bin Zhang, Sitan Feng, Chong Liu","doi":"10.1038/s41435-024-00286-3","DOIUrl":"10.1038/s41435-024-00286-3","url":null,"abstract":"This study aimed to analyze single-cell sequencing data to investigate immune cell interactions in ankylosing spondylitis (AS) and ulcerative colitis (UC). Vertebral bone marrow blood was collected from three AS patients for 10X single-cell sequencing. Analysis of single-cell data revealed distinct cell types in AS and UC patients. Cells significantly co-expressing immune cells (P < 0.05) were subjected to communication analysis. Overlapping genes of these co-expressing immune cells were subjected to GO and KEGG analyses. Key genes were identified using STRING and Cytoscape to assess their correlation with immune cell expression. The results showed the significance of neutrophils in both diseases (P < 0.01), with notable interactions identified through communication analysis. XBP1 emerged as a Hub gene for both diseases, with AUC values of 0.760 for AS and 0.933 for UC. Immunohistochemistry verified that the expression of XBP1 was significantly lower in the AS group and significantly greater in the UC group than in the control group (P < 0.01). This finding highlights the critical role of neutrophils in both AS and UC, suggesting the presence of shared immune response elements. The identification of XBP1 as a potential therapeutic target offers promising intervention avenues for both diseases.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 4","pages":"324-335"},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765878","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

Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy 验证与急性髓性白血病诱导化疗后感染事件有关的先天性免疫基因变异。

IF 5 3区医学

Genes and immunity Pub Date : 2024-07-09 DOI: 10.1038/s41435-024-00285-4

Ulf Schnetzke, Mike Fischer, Christoph Röllig, André Scherag, Heidi Altmann, Friedrich Stölzel, Nael Alakel, Martin Bornhäuser, Andreas Hochhaus, Sebastian Scholl

{"title":"Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy","authors":"Ulf Schnetzke, Mike Fischer, Christoph Röllig, André Scherag, Heidi Altmann, Friedrich Stölzel, Nael Alakel, Martin Bornhäuser, Andreas Hochhaus, Sebastian Scholl","doi":"10.1038/s41435-024-00285-4","DOIUrl":"10.1038/s41435-024-00285-4","url":null,"abstract":"Infectious events, such as sepsis and invasive fungal disease (IFD), pose significant risks in patients with acute myeloid leukemia (AML). Previous studies, including our own, have suggested a potential role of single nucleotide polymorphisms (SNPs) within the innate immune system in influencing individual infection susceptibility. However, many of these associations lack validation in independent cohorts. This study sought to validate the impact of 11 candidate SNPs across 6 genes (TLR2, TLR4, Dectin-1, DC-SIGN, PTX3, L-Ficolin) in an independent cohort of patients. Two cohorts with newly diagnosed AML patients receiving intensive induction chemotherapy were analyzed: a stratification cohort comprising 186 patients and a validation cohort consisting of 138 patients. Multiple SNPs in each cohort were found to be associated to infectious complications, notably the DC-SIGN SNP rs4804800 demonstrated a significant association with sepsis in both cohorts. SNPs within the PTX3 and Dectin-1 genes were linked to IFD development in one cohort each. This study represents the first validation study of candidate genes associated with infectious events in AML patients after intensive induction chemotherapy. Identifying genetic predispositions to infections could significantly impact the management of antimicrobial prophylaxis and treatment in AML patients.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 4","pages":"317-323"},"PeriodicalIF":5.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-024-00285-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563233","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

SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells SARS-CoV-2 病毒在肺泡巨噬细胞中的持续存在受 IFN-γ 和 NK 细胞的控制。

IF 5 3区医学

Genes and immunity Pub Date : 2024-06-26 DOI: 10.1038/s41435-024-00284-5

Emma Beaumont, Michaela Müller-Trutwin, Nicolas Huot

引用次数: 0

The ability of microRNAs to regulate the immune response in ischemia/reperfusion inflammatory pathways microRNA 在缺血/再灌注炎症途径中调节免疫反应的能力。

IF 5 3区医学

Genes and immunity Pub Date : 2024-06-22 DOI: 10.1038/s41435-024-00283-6

Peter Artimovič, Ivana Špaková, Ema Macejková, Timea Pribulová, Miroslava Rabajdová, Mária Mareková, Martina Zavacká

引用次数: 0