Genes and immunity最新文献_第4页

Osteogenesis imperfecta type 10 and the cellular scaffolds underlying common immunological diseases 10 型成骨不全症和常见免疫疾病的细胞支架。

IF 5 3区医学

Genes and immunity Pub Date : 2024-05-29 DOI: 10.1038/s41435-024-00277-4

Alan Herbert

{"title":"Osteogenesis imperfecta type 10 and the cellular scaffolds underlying common immunological diseases","authors":"Alan Herbert","doi":"10.1038/s41435-024-00277-4","DOIUrl":"10.1038/s41435-024-00277-4","url":null,"abstract":"Osteogenesis imperfecta type 10 (OI10) is caused by loss of function codon variants in the gene SERPINH1 that encodes heat shock protein 47 (HSP47), rather than in a gene specifying bone formation. The HSP47 variants disrupt the folding of both collagen and the endonuclease IRE1α (inositol-requiring enzyme 1α) that splices X-Box Binding Protein 1 (XBP1) mRNA. Besides impairing bone development, variants likely affect osteoclast differentiation. Three distinct biochemical scaffold play key roles in the differentiation and regulated cell death of osteoclasts. These scaffolds consist of non-templated protein modifications, ordered lipid arrays, and protein filaments. The scaffold components are specified genetically, but assemble in response to extracellular perturbagens, pathogens, and left-handed Z-RNA helices encoded genomically by flipons. The outcomes depend on interactions between RIPK1, RIPK3, TRIF, and ZBP1 through short interaction motifs called RHIMs. The causal HSP47 nonsynonymous substitutions occur in a novel variant leucine repeat region (vLRR) that are distantly related to RHIMs. Other vLRR protein variants are causal for a variety of different mendelian diseases. The same scaffolds that drive mendelian pathology are associated with many other complex disease outcomes. Their assembly is triggered dynamically by flipons and other context-specific switches rather than by causal, mendelian, codon variants.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 4","pages":"265-276"},"PeriodicalIF":5.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174301","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-derived immunosenescence index for predicting outcome and drug sensitivity in patients with skin cutaneous melanoma 用于预测皮肤黑色素瘤患者预后和药物敏感性的机器学习衍生免疫衰老指数

IF 5 3区医学

Genes and immunity Pub Date : 2024-05-29 DOI: 10.1038/s41435-024-00278-3

Linyu Zhu, Lvya Zhang, Junhua Qi, Zhiyu Ye, Gang Nie, Shaolong Leng

{"title":"Machine learning-derived immunosenescence index for predicting outcome and drug sensitivity in patients with skin cutaneous melanoma","authors":"Linyu Zhu, Lvya Zhang, Junhua Qi, Zhiyu Ye, Gang Nie, Shaolong Leng","doi":"10.1038/s41435-024-00278-3","DOIUrl":"10.1038/s41435-024-00278-3","url":null,"abstract":"The functions of immunosenescence are closely related to skin cutaneous melanoma (SKCM). The aim of this study is to uncover the characteristics of immunosenescence index (ISI) to identify novel biomarkers and potential targets for treatment. Firstly, integrated bioinformatics analysis was carried out to identify risk prognostic genes, and their expression and prognostic value were evaluated. Then, we used the computational algorithm to estimate ISI. Finally, the distribution characteristics and clinical significance of ISI in SKCM by using multi-omics analysis. Patients with a lower ISI had a favorable survival rate, lower chromosomal instability, lower somatic copy-number alterations, lower somatic mutations, higher immune infiltration, and sensitive to immunotherapy. The ISI exhibited robust, which was validated in multiple datasets. Besides, the ISI is more effective than other published signatures in predicting survival outcomes for patients with SKCM. Single-cell analysis revealed higher ISI was specifically expressed in monocytes, and correlates with the differentiation fate of monocytes in SKCM. Besides, individuals exhibiting elevated ISI levels could potentially receive advantages from chemotherapy, and promising compounds with the potential to target high ISI were recognized. The ISI model is a valuable tool in categorizing SKCM patients based on their prognosis, gene mutation signatures, and response to immunotherapy.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 3","pages":"219-231"},"PeriodicalIF":5.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174296","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

Integrated analyses reveal the diagnostic and predictive values of COL5A2 and association with immune environment in Crohn’s disease 综合分析揭示了 COL5A2 的诊断和预测价值以及与克罗恩病免疫环境的关联。

IF 5 3区医学

Genes and immunity Pub Date : 2024-05-24 DOI: 10.1038/s41435-024-00276-5

Tingting Zhong, Xiaoqing Cheng, Qianru Gu, Guoxiang Fu, Yihong Wang, Yujie Jiang, Jiaqi Xu, Zhinong Jiang

{"title":"Integrated analyses reveal the diagnostic and predictive values of COL5A2 and association with immune environment in Crohn’s disease","authors":"Tingting Zhong, Xiaoqing Cheng, Qianru Gu, Guoxiang Fu, Yihong Wang, Yujie Jiang, Jiaqi Xu, Zhinong Jiang","doi":"10.1038/s41435-024-00276-5","DOIUrl":"10.1038/s41435-024-00276-5","url":null,"abstract":"The pathogenesis of Crohn’s disease (CD) involves abnormal immune cell infiltration and dysregulated immune response. Therefore, thorough research on immune cell abnormalities in CD is crucial for improved treatment of this disease. Single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data of CD were obtained from the Gene Expression Omnibus (GEO) database. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), weighted gene co-expression network analysis (WGCNA), protein–protein interaction (PPI) networks evaluated the proportion of immune infiltrating cells, constructed co-expression network and identified key genes, respectively. Based on the dataset (GSE134809), 15 cell clusters were defined and labeled as different cell types. Among the 11 modules, the yellow module had the closest relationship with plasma cells (cluster 5). Confirmed using RNA sequencing and IHC assay, the expression of COL5A2 in CD samples was higher than that in control samples. Furthermore, the COL5A2 protein expression remarkably decreased in the group of patients who responded to anti–tumor necrosis factor (TNF) treatments, compared to the non-response group. The comprehensive analyses described here provided novel insight into the landscape of CD-associated immune environment. In addition, COL5A2 were identified as potential diagnostic indicators for CD, as well as promising predictive markers for CD patients.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 3","pages":"209-218"},"PeriodicalIF":5.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-024-00276-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093362","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

TIMP-1 is an activator of MHC-I expression in myeloid dendritic cells with implications for tumor immunogenicity TIMP-1 是骨髓树突状细胞中 MHC-I 表达的激活剂，对肿瘤免疫原性有影响。

IF 5 3区医学

Genes and immunity Pub Date : 2024-05-22 DOI: 10.1038/s41435-024-00274-7

Miriam Langguth, Eleftheria Maranou, Saara A. Koskela, Oskar Elenius, Roosa E. Kallionpää, Eva-Maria Birkman, Otto I. Pulkkinen, Maria Sundvall, Marko Salmi, Carlos R. Figueiredo

{"title":"TIMP-1 is an activator of MHC-I expression in myeloid dendritic cells with implications for tumor immunogenicity","authors":"Miriam Langguth, Eleftheria Maranou, Saara A. Koskela, Oskar Elenius, Roosa E. Kallionpää, Eva-Maria Birkman, Otto I. Pulkkinen, Maria Sundvall, Marko Salmi, Carlos R. Figueiredo","doi":"10.1038/s41435-024-00274-7","DOIUrl":"10.1038/s41435-024-00274-7","url":null,"abstract":"Immune checkpoint therapies (ICT) for advanced solid tumors mark a new milestone in cancer therapy. Yet their efficacy is often limited by poor immunogenicity, attributed to inadequate priming and generation of antitumor T cells by dendritic cells (DCs). Identifying biomarkers to enhance DC functions in such tumors is thus crucial. Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), recognized for its influence on immune cells, has an underexplored relationship with DCs. Our research reveals a correlation between high TIMP1 levels in metastatic melanoma and increased CD8 + T cell infiltration and survival. Network studies indicate a functional connection with HLA genes. Spatial transcriptomic analysis of a national melanoma cohort revealed that TIMP1 expression in immune compartments associates with an HLA-A/MHC-I peptide loading signature in lymph nodes. Primary human and bone-marrow-derived DCs secrete TIMP-1, which notably increases MHC-I expression in classical type 1 dendritic cells (cDC1), especially under melanoma antigen exposure. TIMP-1 affects the immunoproteasome/TAP complex, as seen by upregulated PSMB8 and TAP-1 levels of myeloid DCs. This study uncovers the role of TIMP-1 in DC-mediated immunogenicity with insights into CD8 + T cell activation, providing a foundation for mechanistic exploration and highlighting its potential as a new target for combinatorial immunotherapy to enhance ICT effectiveness.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 3","pages":"188-200"},"PeriodicalIF":5.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-024-00274-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081226","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

HER2-targeting CAR-T cells show highly efficient anti-tumor activity against glioblastoma both in vitro and in vivo HER2靶向CAR-T细胞在体外和体内对胶质母细胞瘤都显示出高效的抗肿瘤活性。

IF 5 3区医学

Genes and immunity Pub Date : 2024-05-03 DOI: 10.1038/s41435-024-00275-6

Xueying Li, Lifen Zhao, Wenzhe Li, Peng Gao, Nianzhu Zhang

{"title":"HER2-targeting CAR-T cells show highly efficient anti-tumor activity against glioblastoma both in vitro and in vivo","authors":"Xueying Li, Lifen Zhao, Wenzhe Li, Peng Gao, Nianzhu Zhang","doi":"10.1038/s41435-024-00275-6","DOIUrl":"10.1038/s41435-024-00275-6","url":null,"abstract":"Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Current treatment options for GBM include surgical resection, radiation, and chemotherapy, which predominantly slow cancer growth and reduce symptoms, resulting in a 5-year survival rate of no more than 10%. Chimeric antigen receptor (CAR) T-cell therapy is a new class of cellular immunotherapy that has made great progress in treating malignant tumors. Human epidermal growth factor receptor 2 (HER2) is overexpressed in GBM and may provide a potential therapeutic target for GBM treatment. In this study, we constructed third-generation CAR-T cells targeting the HER2 antigen in GBM. HER2-CAR-T cells showed effective anti-tumor activity both in vitro and in vivo. Furthermore, HER2-specific CAR-T cells exhibited strong cytotoxicity and cytokine-secreting abilities against GBM cells in vitro. Anti-HER2 CAR-T cells also exhibited increased cytotoxicity with increasing effector-to-target ratios. Anti-HER2 CAR-T cells delivered via peritumoral injection successfully stunted tumor progression in vivo. Moreover, peritumoral intravenous administration of anti-HER2 CAR-T cells resulted in therapeutic improvement against GBM cells compared with intravenous administration. In conclusion, our study shows that HER2 CAR-T cells represent an emerging immunotherapy for treating GBM.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 3","pages":"201-208"},"PeriodicalIF":5.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-024-00275-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851071","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

Oxidized phospholipids during microbial challenge: friend or foe? 微生物挑战过程中的氧化磷脂：敌还是友？

IF 5 3区医学

Genes and immunity Pub Date : 2024-04-22 DOI: 10.1038/s41435-024-00273-8

Henrique G. Colaço, Kelsey Voss

引用次数: 0

MDSC expansion during HIV infection: regulators, ART and immune reconstitution 艾滋病毒感染期间 MDSC 的扩增：调节器、抗逆转录病毒疗法和免疫重建

IF 5 3区医学

Genes and immunity Pub Date : 2024-04-11 DOI: 10.1038/s41435-024-00272-9

Mahmoud Mohammad Yaseen, Nizar Mohammad Abuharfeil, Homa Darmani

引用次数: 0

Correction: Same name, different game?—How ontogeny shapes classical monocyte phenotypes 更正：同样的名字，不同的游戏？--本体如何塑造经典的单核细胞表型。

IF 5 3区医学

Genes and immunity Pub Date : 2024-04-09 DOI: 10.1038/s41435-024-00269-4

Lisabeth Pimenov, Azuah Lucrecia Gonzalez, Amanda C. Doran, Sylvia Knapp

引用次数: 0

Transcriptomic meta-analysis characterizes molecular commonalities between psoriasis and obesity 转录组元分析描述了银屑病与肥胖之间的分子共性。

IF 5 3区医学

Genes and immunity Pub Date : 2024-04-05 DOI: 10.1038/s41435-024-00271-w

Charalabos Antonatos, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos

{"title":"Transcriptomic meta-analysis characterizes molecular commonalities between psoriasis and obesity","authors":"Charalabos Antonatos, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos","doi":"10.1038/s41435-024-00271-w","DOIUrl":"10.1038/s41435-024-00271-w","url":null,"abstract":"Despite the abundance of epidemiological evidence for the high comorbid rate between psoriasis and obesity, systematic approaches to common inflammatory mechanisms have not been adequately explored. We performed a meta-analysis of publicly available RNA-sequencing datasets to unveil putative mechanisms that are postulated to exacerbate both diseases, utilizing both late-stage, disease-specific meta-analyses and consensus gene co-expression network (cWGCNA). Single-gene meta-analyses reported several common inflammatory mechanisms fostered by the perturbed expression profile of inflammatory cells. Assessment of gene overlaps between both diseases revealed significant overlaps between up- (n = 170, P value = 6.07 × 10−65) and down-regulated (n = 49, P value = 7.1 × 10−7) genes, associated with increased T cell response and activated transcription factors. Our cWGCNA approach disentangled 48 consensus modules, associated with either the differentiation of leukocytes or metabolic pathways with similar correlation signals in both diseases. Notably, all our analyses confirmed the association of the perturbed T helper (Th)17 differentiation pathway in both diseases. Our novel findings through whole transcriptomic analyses characterize the inflammatory commonalities between psoriasis and obesity implying the assessment of several expression profiles that could serve as putative comorbid disease progression biomarkers and therapeutic interventions.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 3","pages":"179-187"},"PeriodicalIF":5.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140737220","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

Comparative single-cell transcriptomic profile of hybrid immunity induced by adenovirus vector-based COVID-19 vaccines 基于腺病毒载体的 COVID-19 疫苗诱导的混合免疫的单细胞转录组比较图谱

IF 5 3区医学

Genes and immunity Pub Date : 2024-04-03 DOI: 10.1038/s41435-024-00270-x

Melissa García-Vega, Hui Wan, Mónica Reséndiz-Sandoval, Diana Hinojosa-Trujillo, Olivia Valenzuela, Verónica Mata-Haro, Freddy Dehesa-Canseco, Mario Solís-Hernández, Harold Marcotte, Qiang Pan-Hammarström, Jesús Hernández

{"title":"Comparative single-cell transcriptomic profile of hybrid immunity induced by adenovirus vector-based COVID-19 vaccines","authors":"Melissa García-Vega, Hui Wan, Mónica Reséndiz-Sandoval, Diana Hinojosa-Trujillo, Olivia Valenzuela, Verónica Mata-Haro, Freddy Dehesa-Canseco, Mario Solís-Hernández, Harold Marcotte, Qiang Pan-Hammarström, Jesús Hernández","doi":"10.1038/s41435-024-00270-x","DOIUrl":"10.1038/s41435-024-00270-x","url":null,"abstract":"In this study, antibody response and a single-cell RNA-seq analysis were conducted on peripheral blood mononuclear cells from five different groups: naïve subjects vaccinated with AZD1222 (AZ) or Ad5-nCoV (Cso), individuals previously infected and later vaccinated (hybrid) with AZD1222 (AZ-hb) or Ad5-nCoV (Cso-hb), and those who were infected and had recovered from COVID-19 (Inf). The results showed that AZ induced more robust neutralizing antibody responses than Cso. The single-cell RNA data revealed a high frequency of memory B cells in the Cso and Cso-hb. In contrast, AZ and AZ-hb groups exhibited the highest proportion of activated naïve B cells expressing CXCR4. Transcriptomic analysis of CD4+ and CD8+ T cells demonstrated a heterogeneous response following vaccination, hybrid immunity, or natural infection. However, a single dose of Ad5-nCoV was sufficient to strongly activate CD4+ T cells (naïve and memory) expressing ANX1 and FOS, similar to the hybrid response observed with AZ. An interesting finding was the robust activation of a subset of CD8+ T cells expressing GZMB, GZMH, and IFNG genes in the Cso-hb group. Our findings suggest that both vaccines effectively stimulated the cellular immune response; however, the Ad5-nCoV induced a more robust CD8+ T-cell response in previously infected individuals.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 2","pages":"158-167"},"PeriodicalIF":5.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559882","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