Genes and immunity最新文献_第3页

Lipid metabolism-related genes are involved in the formation of macrophage extracellular traps in allergic airway inflammation. 脂质代谢相关基因参与变态反应性气道炎症中巨噬细胞胞外陷阱的形成。

IF 5 3区医学

Genes and immunity Pub Date : 2025-04-01 Epub Date: 2025-01-09 DOI: 10.1038/s41435-025-00319-5

Haixia Wang, Bin Ma, Yuanmin Jia, Hui Wei, Danyang Li, Junlian Gu, Ou Chen, Shouwei Yue

{"title":"Lipid metabolism-related genes are involved in the formation of macrophage extracellular traps in allergic airway inflammation.","authors":"Haixia Wang, Bin Ma, Yuanmin Jia, Hui Wei, Danyang Li, Junlian Gu, Ou Chen, Shouwei Yue","doi":"10.1038/s41435-025-00319-5","DOIUrl":"10.1038/s41435-025-00319-5","url":null,"abstract":"Recent studies have highlighted the critical role of lipid metabolism in macrophages concerning lung inflammation. However, it remains unclear whether lipid metabolism is involved in macrophage extracellular traps (METs). We analyzed the GSE40885 dataset from the GEO database using weighted correlation network analysis (WGCNA) and further selection using the least absolute shrinkage and selection operator (LASSO) regression. We identified ABCA1, SLC44A2, and C3 as key genes jointly involved in lipid metabolism and METs. Additionally, immune infiltration analysis was performed using the Xcell and CIBERSORT algorithms, while single-cell transcriptome analysis was utilized using data from the Tabula Muris database. The expression of key genes was validated in external datasets (GSE42606, GSE27066, GSE137268, and GSE256534). Notably, our results indicated that ABCA1 expression was elevated in patients experiencing acute asthma exacerbations, which aligned with its expression trend in lipopolysaccharide (LPS)-induced macrophages. However, ABCA1 expression was reduced in cases of chronic and severe asthma. Results from immunofluorescence (IF), SYTOX Green staining, and Western blot analyses suggested that ABCA1 may play a role in the formation of METs both in vivo and in vitro. In conclusion, this study indicates that ABCA1 may be involved in METs. ABCA1 may represent a promising therapeutic target for asthma.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":"96-110"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947694","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

Long noncoding RNA PARAL1 regulates myeloid dendritic cell differentiation and TLR signaling. 长链非编码RNA PARAL1调控髓树突状细胞分化和TLR信号传导。

IF 5 3区医学

Genes and immunity Pub Date : 2025-04-01 Epub Date: 2025-02-26 DOI: 10.1038/s41435-025-00323-9

Raza Ali Naqvi, Araceli Valverde, Deepak Shukla, Afsar Naqvi

{"title":"Long noncoding RNA PARAL1 regulates myeloid dendritic cell differentiation and TLR signaling.","authors":"Raza Ali Naqvi, Araceli Valverde, Deepak Shukla, Afsar Naqvi","doi":"10.1038/s41435-025-00323-9","DOIUrl":"10.1038/s41435-025-00323-9","url":null,"abstract":"Dendritic cells (DCs) are professional antigen presentation cells (APCs) that bridge innate and adaptive immune functions to contain pathogenic threats. Long noncoding RNAs (lncRNAs) are implicated in regulating biological processes, including inflammation and immunity. However, the knowledge of myeloid DC-expressed lncRNA repertoire and their regulatory functions is limited. Here we profiled lncRNA expression kinetics during monocyte-to-DC (moDC) differentiation and characterized their functional roles. Our RNA-seq data identified a repertoire of differentially expressed lncRNAs associated with moDC differentiation and a large subset of these lncRNAs are distinct from M1 or M2 macrophages. We selected two DC-enriched lncRNAs and observed that PARAL1 silencing, or overexpression modulates DC surface markers expression. Importantly, PARAL1 RNAi significantly reduced, while its overexpression upregulated the levels of multiple TLRs. Upon treatment with TLR agonists PARAL1 knockdown cells exhibit reduced NF-κB, IRF3 and IRF7 phosphorylation substantiating its role in potentiating TLR signaling. Mechanistically, PARAL1 silencing showed significant downregulation of multiple NF-κB-induced genes and time-dependent inhibition of proinflammatory cytokine secretion upon challenge with TLR agonists. Finally, PARAL1 RNAi in DCs significantly impaired antigen processing and presentation to T cells. Overall, this study characterized novel functions of PARAL1 in regulating DC differentiation, TLR-dependent innate immunity and activation of adaptive immune response.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":"151-165"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500543","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

Roles of immunoglobulin GM and KM allotypes and Fcγ receptor 2 A genotypes in humoral immunity to a conserved microbial polysaccharide in pulmonary diseases. 免疫球蛋白GM和KM异体型和Fcγ受体2a基因型在肺部疾病对保守微生物多糖的体液免疫中的作用

IF 5 3区医学

Genes and immunity Pub Date : 2025-04-01 Epub Date: 2025-01-07 DOI: 10.1038/s41435-024-00318-y

Janardan P Pandey, Paul J Nietert, Aryan M Namboodiri, Christine Kimball, Patrick A Flume

{"title":"Roles of immunoglobulin GM and KM allotypes and Fcγ receptor 2 A genotypes in humoral immunity to a conserved microbial polysaccharide in pulmonary diseases.","authors":"Janardan P Pandey, Paul J Nietert, Aryan M Namboodiri, Christine Kimball, Patrick A Flume","doi":"10.1038/s41435-024-00318-y","DOIUrl":"10.1038/s41435-024-00318-y","url":null,"abstract":"Immunoglobulin GM (γ marker) and KM (κ marker) allotypes-encoded by immunoglobulin heavy chain G (IGHG) and immunoglobulin κ constant (IGKC) genes-have been shown to be associated with immune responsiveness to a variety of self and nonself antigens. The aim of the present investigation was to determine whether allelic variation at the GM and KM loci was associated with antibody responsiveness to poly-N-acetyl-D-glucosamine (PNAG), a broadly-conserved surface polysaccharide expressed by many microbial pathogens. In addition, we wished to determine whether Fcγ receptor 2 A (FCGR2A) genotypes, which have been shown to be risk factors for some pathogens, also influenced antibody responses to PNAG. DNA from 257 patients with various pulmonary diseases (PD) was genotyped for several GM, KM, and FCGR2A alleles, and plasma were characterized for anti-PNAG IgG antibodies. The levels of IgG4 antibodies to PNAG were associated with FCGR2A genotypes (p = 0.01). Also, KM and FCGR2A alleles epistatically contributed to anti-PNAG IgG3 antibody responses: subjects with KM 1/1 or KM 1/3 and homozygous for the R allele of FCGR2A had the highest levels of anti-PNAG IgG3 antibodies compared to all other genotype combinations. If confirmed by larger studies, these results are potentially relevant to immunotherapy against many PNAG-expressing infectious pathogens.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":"91-95"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947697","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

Multi-omics clustering analysis carries out the molecular-specific subtypes of thyroid carcinoma: implicating for the precise treatment strategies. 多组学聚类分析对甲状腺癌的分子特异性亚型进行分析，为精确的治疗策略提供依据。

IF 5 3区医学

Genes and immunity Pub Date : 2025-04-01 Epub Date: 2025-03-04 DOI: 10.1038/s41435-025-00322-w

Zhenglin Wang, Qijun Han, Xianyu Hu, Xu Wang, Rui Sun, Siwei Huang, Wei Chen

{"title":"Multi-omics clustering analysis carries out the molecular-specific subtypes of thyroid carcinoma: implicating for the precise treatment strategies.","authors":"Zhenglin Wang, Qijun Han, Xianyu Hu, Xu Wang, Rui Sun, Siwei Huang, Wei Chen","doi":"10.1038/s41435-025-00322-w","DOIUrl":"10.1038/s41435-025-00322-w","url":null,"abstract":"Thyroid cancer (TC) is the most prevalent endocrine malignancy worldwide. This study aimed to explore the molecular subtypes and improve the selection of targeted therapies. We used multi-omics data from 539 patients with DNA methylation, gene mutations, mRNA, lncRNA, and miRNA expressions. This study employed consensus clustering algorithms to identify molecular subtypes and used various bioinformatics tools to analyze genetic alterations, signaling pathways, immune infiltration, and responses to chemotherapy and immunotherapy. Two prognostically relevant TC subtypes, CS1 and CS2, were identified. CS2 was associated with a poorer prognosis of shorter progression-free survival times (P < 0.001). CS1 exhibited higher copy number alterations but a lower tumor mutation burden than CS2. CS2 exhibited activation in cell proliferation and immune-related pathways. Drug sensitivity analysis indicated CS2's higher sensitivity to cisplatin, doxorubicin, paclitaxel, and sunitinib, whereas CS1 was more sensitive to bicalutamide and FH535. The different activated pathways and sensitivity to drugs for the subtypes were further validated in an external cohort. Twenty-four paired tumors and adjacent normal tissues by immunohistochemical staining further demonstrated the prognostic value of CXCL17. In conclusion, we identified two distinct molecular subtypes of TC with significant implications for prognosis, genetic alterations, pathway activation, and treatment response.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":"137-150"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556633","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 need for Cre-loci controls in conditional mouse experiments: Mrp8-cre transgene predisposes mice to antibody-induced arthritis. 条件小鼠实验中对cre位点对照的需要：Mrp8-cre转基因使小鼠易患抗体诱导的关节炎。

IF 5 3区医学

Genes and immunity Pub Date : 2025-04-01 Epub Date: 2024-12-04 DOI: 10.1038/s41435-024-00313-3

Zhongwei Xu, Laura Romero-Castillo, Àlex Moreno-Giró, Rajan Kumar Pandey, Rikard Holmdahl

引用次数: 0

Comprehensive analysis of autophagy status and its relationship with immunity and inflammation in ischemic stroke through integrated transcriptomic and single-cell sequencing. 综合转录组学和单细胞测序分析缺血性脑卒中自噬状态及其与免疫和炎症的关系。

IF 5 3区医学

Genes and immunity Pub Date : 2025-04-01 Epub Date: 2025-01-18 DOI: 10.1038/s41435-025-00320-y

Xiaole Zhu, Zhongman Zhang, Yi Zhu, Yanlong Chen, Wei Li, Huae Xu, Xufeng Chen

{"title":"Comprehensive analysis of autophagy status and its relationship with immunity and inflammation in ischemic stroke through integrated transcriptomic and single-cell sequencing.","authors":"Xiaole Zhu, Zhongman Zhang, Yi Zhu, Yanlong Chen, Wei Li, Huae Xu, Xufeng Chen","doi":"10.1038/s41435-025-00320-y","DOIUrl":"10.1038/s41435-025-00320-y","url":null,"abstract":"Ischemic stroke (IS) significantly impacts patients' health and quality of life, with the roles of autophagy and autophagy-related genes in IS still not fully understood. In this study, IS datasets were retrieved from the GEO database. Autophagy-related genes(ARGs) were identified and screened for differential expression. A prediction model was constructed using machine learning algorithm. WGCNA was employed to analyze differential regulation modules among different clusters of stroke patients. The analysis results were validated using single-cell sequencing data. Finally, autophagy hub genes were validated in an external cohort and an IS mouse model. We observed suppressed autophagy states in IS patients. A diagnostic model with good clinical efficacy for stroke diagnosis was constructed based on the selected key genes (AUC = 0.87). Consensus clustering identified two IS subtypes with distinct gene expression patterns and immune cell infiltration. scRNA-seq data analysis confirmed downregulation of pexophagy in IS. CellChat analysis identified key signaling pathways and intercellular interactions related to pexophagy. Validation in an external cohort and IS mouse model confirmed differential gene expression, supporting the involvement of pexophagy in IS pathogenesis. The identified key genes, molecular subtypes, and cellular interactions provide a foundation for further research into targeted therapies and precision medicine approaches for IS patients.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":"111-123"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004271","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

Next-generation DC vaccines with an immunogenic trajectory against cancer: therapeutic opportunities vs. resistance mechanisms. 具有抗癌免疫原性轨迹的下一代直流电疫苗：治疗机会与抗药性机制。

IF 5 3区医学

Genes and immunity Pub Date : 2025-04-01 DOI: 10.1038/s41435-024-00294-3

Jenny Sprooten, Abhishek D Garg

引用次数: 0

Immune pathogenic response landscape of acute posterior multifocal placoid pigment epitheliopathy revealed by scRNA sequencing. scRNA测序揭示急性后部多灶性placoid色素上皮病的免疫致病反应景观。

IF 5 3区医学

Genes and immunity Pub Date : 2025-04-01 Epub Date: 2025-01-07 DOI: 10.1038/s41435-024-00316-0

Jingyang Liu, Qingge Guo, Guangming Liu, Weiping Wang, Xiuxiu Jin, Bingtao Hao, Bo Lei

{"title":"Immune pathogenic response landscape of acute posterior multifocal placoid pigment epitheliopathy revealed by scRNA sequencing.","authors":"Jingyang Liu, Qingge Guo, Guangming Liu, Weiping Wang, Xiuxiu Jin, Bingtao Hao, Bo Lei","doi":"10.1038/s41435-024-00316-0","DOIUrl":"10.1038/s41435-024-00316-0","url":null,"abstract":"Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an exceptionally rare inflammatory disorder affecting choroid and retinal pigment epithelial (RPE) cells. Although recent studies suggest an immune-driven nature, the underlying etiology of APMPPE remains elusive. In this study, we conducted a comprehensive investigation on the peripheral blood mononuclear cells (PBMCs) profile of an APMPPE patient using single-cell RNA sequencing. Our analysis revealed striking transcriptional alterations in monocytes within the PBMCs, identifying five distinct subpopulations: S100A12, CD16, pro-inflammatory, megakaryocyte-like, and NK-like monocyte subsets. Employing pseudotime inference, we observed a shift in APMPPE monocytes towards differentiation into inflammation-associated pro-inflammatory monocytes and a CD16 monocyte trajectory. Furthermore, we identified IFITM3 as a key player in the immune response driving the pathogenesis of APMPPE. Notably, two disease-relevant subgroups of monocytes, pro-inflammatory and CD16 monocytes, were implicated in APMPPE. CD16 monocytes, in particular, were involved in melanogenesis, suggesting that the abnormal expression of melanin in monocytes might result from autoimmune responses against pigment-enriched RPE cells. This study provided a comprehensive view of immune landscape in APMPPE, shedding light on the previously unrecognized contributions of pro-inflammatory and CD16 monocytes to this autoimmune condition.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":"75-90"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947683","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

Age-dependent gene expression trajectories during early childhood in children at increased risk for type 1 diabetes. 1型糖尿病风险增加的儿童早期年龄依赖性基因表达轨迹

IF 5 3区医学

Genes and immunity Pub Date : 2025-04-01 Epub Date: 2025-03-20 DOI: 10.1038/s41435-025-00324-8

Ivo Zeller, Andreas Weiss, Sandra Hummel, Anette-Gabriele Ziegler, Ezio Bonifacio

{"title":"Age-dependent gene expression trajectories during early childhood in children at increased risk for type 1 diabetes.","authors":"Ivo Zeller, Andreas Weiss, Sandra Hummel, Anette-Gabriele Ziegler, Ezio Bonifacio","doi":"10.1038/s41435-025-00324-8","DOIUrl":"10.1038/s41435-025-00324-8","url":null,"abstract":"Early childhood is a period of rapid growth and immune system development. It is also critical for type 1 diabetes (T1D) autoimmunity, which has a peak incidence between 1 and 2 years of age. Here, we investigated age-related longitudinal gene expression changes in peripheral blood mononuclear cells from children aged 3 months to 3 years who had an increased genetic risk for T1D, aiming to delineate gene expression trajectories and identify patterns potentially linked to the development of islet autoimmunity. We found 2 432 genes (12.5% of analyzed genes) to exhibit significant temporal dynamics in the first 3 years of life. These genes were grouped into six major clusters each demonstrating distinct expression trajectories of consistent increase or decrease with age, as well as U-shaped, and inverted U-shaped age-related patterns. Notably, genes in clusters with U-shaped expression trajectories, which mirrored the incidence of islet autoantibodies, were enriched for T1D susceptibility genes, particularly within the Major Histocompatibility Complex (MHC) region. This study underscores the dynamic nature of gene expression in early childhood and its potential connection to T1D risk.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":"173-177"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669636","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

Annexin A1 regulates inflammatory-immune response and reduces pancreatic and extra- pancreatic injury during severe acute pancreatitis. Annexin A1 可调节炎症免疫反应，减少重症急性胰腺炎时胰腺和胰腺外的损伤。

IF 5 3区医学

Genes and immunity Pub Date : 2025-04-01 Epub Date: 2025-03-01 DOI: 10.1038/s41435-025-00321-x

Shizhao Lin, Feihong Liang, Changgan Chen, Jiajing Lin, Yuwei Wu, Zelin Hou, Heguang Huang, Haizong Fang, Yu Pan

{"title":"Annexin A1 regulates inflammatory-immune response and reduces pancreatic and extra- pancreatic injury during severe acute pancreatitis.","authors":"Shizhao Lin, Feihong Liang, Changgan Chen, Jiajing Lin, Yuwei Wu, Zelin Hou, Heguang Huang, Haizong Fang, Yu Pan","doi":"10.1038/s41435-025-00321-x","DOIUrl":"10.1038/s41435-025-00321-x","url":null,"abstract":"Severe acute pancreatitis (SAP) poses significant challenges due to its complex pathophysiology, which includes inflammatory-immune responses that cause considerable damage to both the pancreas and other tissues. In this study, we explored the role of Annexin A1 (Anxa1), a glucocorticoid-regulated protein recognized for its anti-inflammatory properties, in regulating inflammation during acute pancreatitis. Using flow cytometry, single-cell RNA sequencing, and gene expression analysis, we examined how Anxa1 expression is regulated in myeloid cells throughout acute pancreatitis, employing various animal models to evaluate the consequences of modulating Anxa1 on injuries induced by SAP. Our findings revealed dynamic regulation of Anxa1 expression in myeloid cells, with mice lacking Anxa1 exhibiting worsened pancreatic injury and heightened systemic inflammation, resulting in significant damage to extra-pancreatic organs such as the lungs, liver, and kidneys. In contrast, treatment with Ac2-26, a synthetic peptide derived from Anxa1, effectively mitigated both pancreatic and extra-pancreatic inflammation and tissue damage. Overall, this study highlights the critical role of Anxa1 in modulating inflammatory responses during acute pancreatitis. Targeting Anxa1 presents a promising therapeutic strategy to mitigate pancreatic injury and prevent systemic complications associated with severe acute pancreatitis.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":"124-136"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536970","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