Genes and immunity最新文献_第6页

Correction: Roles of TULA-family proteins in T cells and autoimmune diseases 更正：TULA 家族蛋白在 T 细胞和自身免疫性疾病中的作用。

IF 5 3区医学

Genes and immunity Pub Date : 2024-12-09 DOI: 10.1038/s41435-024-00311-5

Hua Wang, Patrick Concannon, Yan Ge

引用次数: 0

GXYLT2: an emerging therapeutic target and predictive biomarker for anti-PD-1 efficacy in clear cell renal cell carcinoma GXYLT2：透明细胞肾细胞癌抗pd -1疗效的新兴治疗靶点和预测性生物标志物

IF 5 3区医学

Genes and immunity Pub Date : 2024-12-05 DOI: 10.1038/s41435-024-00312-4

Tuanjie Guo, Jinyuan Chen, Xiangyin Tan, Heting Tang, Xuan Wang, Siteng Chen, Xiang Wang

{"title":"GXYLT2: an emerging therapeutic target and predictive biomarker for anti-PD-1 efficacy in clear cell renal cell carcinoma","authors":"Tuanjie Guo, Jinyuan Chen, Xiangyin Tan, Heting Tang, Xuan Wang, Siteng Chen, Xiang Wang","doi":"10.1038/s41435-024-00312-4","DOIUrl":"10.1038/s41435-024-00312-4","url":null,"abstract":"There are studies reporting that glucoside xylosyltransferase 2 (GXYLT2) has a role in promoting tumor progression, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, RT-qPCR and western blotting were employed to detect the expression level of GXYLT2. RNA interference assays were used to knock down GXYLT2. CCK-8, wound healing assays, clone formation assays, and Transwell assays were utilized to investigate the function of GXYLT2. Bioinformatics analysis was used to explore the tumor microenvironment and potential biological mechanisms. We found that the expression level of GXYLT2 in ccRCC was higher than that in adjacent normal renal tissues. Patients with high GXYLT2 expression have worse clinical outcomes. Knockdown of GXYLT2 inhibits the proliferation, invasion, migration, and clone formation ability of ccRCC cells. Enrichment analysis uncovered that GXYLT2 participates in Wnt, cell cycle, and actin cytoskeleton regulation signaling pathways. After receiving anti-PD-1 therapy, patients with high GXYLT2 expression had longer progression-free survival compared with those with low GXYLT2 expression. In conclusion, GXYLT2 is a novel potential therapeutic target for ccRCC. Meanwhile, GXYLT2 can be used as a novel marker for predicting immunotherapeutic response.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 1","pages":"27-35"},"PeriodicalIF":5.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784959","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 4.5 3区医学

Genes and immunity Pub 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

The role of NLRP3 and NLRP12 inflammasomes in glioblastoma NLRP3和NLRP12炎症体在胶质母细胞瘤中的作用。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-27 DOI: 10.1038/s41435-024-00309-z

Sushmita Rajkhowa, Sushmita Jha

{"title":"The role of NLRP3 and NLRP12 inflammasomes in glioblastoma","authors":"Sushmita Rajkhowa, Sushmita Jha","doi":"10.1038/s41435-024-00309-z","DOIUrl":"10.1038/s41435-024-00309-z","url":null,"abstract":"Glioblastoma (GBM) is the deadliest malignant brain tumor, with a survival of less than 14 months after diagnosis. The highly invasive nature of GBM makes total surgical resection challenging, leading to tumor recurrence and declined survival. The heterocellular composition of the GBM reprograms its microenvironment, favoring tumor growth, proliferation, and migration. The innate immune cells in the GBM tumor microenvironment, including microglia, astrocytes, and macrophages, express pattern recognition receptors such as NLRs (Nucleotide-binding domain and leucine-rich repeat-containing) that sense pathogen- and damage-associated molecular patterns initiating inflammation. Upon activation, NLRP3 promotes inflammation by NLRP3 inflammasome formation. Auto-proteolytic cleavage and activation of Caspase-1 within the inflammasome leads to caspase-1-mediated cleavage, activation, and conversion of pro-IL-1ß and pro-IL-18 to IL-1ß and IL-18, leading to pyroptosis. In contrast, NLRP12 downregulates inflammatory responses in microglia and macrophages by regulating the NF-κB pathway. NLRP3 and NLRP12 have been implicated in the disease pathophysiology of several cancers with cell-context-dependent, pro- or anti-tumorigenic roles. In this review, we discuss the current literature on the mechanistic roles of NLRP3 and NLRP12 in GBM and the gaps in the scientific literature in the context of GBM pathophysiology with potential for targeted therapeutics.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 6","pages":"541-551"},"PeriodicalIF":5.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739252","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

Neoantigen-specific mRNA/DC vaccines for effective anticancer immunotherapy 用于有效抗癌免疫疗法的新抗原特异性 mRNA/DC 疫苗。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-26 DOI: 10.1038/s41435-024-00305-3

Wenli Zhang, Jiahao Guan, Wenwen Wang, Guo Chen, Li Fan, Zifan Lu

{"title":"Neoantigen-specific mRNA/DC vaccines for effective anticancer immunotherapy","authors":"Wenli Zhang, Jiahao Guan, Wenwen Wang, Guo Chen, Li Fan, Zifan Lu","doi":"10.1038/s41435-024-00305-3","DOIUrl":"10.1038/s41435-024-00305-3","url":null,"abstract":"The development of personalized anticancer vaccines based on neoantigens represents a new direction in cancer immunotherapy. The latest advancement in dendritic cell (DC) tumor vaccine construction involves loading DC with mRNA-encoding neoantigens, which allows for rapid production and is suitable for personalized preparation. Cell-penetrating peptides (CPPs) are emerging as biological delivery systems in which negatively charged nucleic acids can be wound onto the cationic CPP backbone to form nanoscale complexes. This preparation method facilitates standardization. If DC can express and present neoantigen mRNA at high levels, it holds promising application potential. In this study, we developed a neoantigen-mRNA/DC vaccine using candidate neoantigens from mouse colon cancer (MC38) and examined its immune and antitumor effects. The results demonstrated that neoantigen-mRNA/DC vaccines induced strong T cell immune responses and exhibited significant antitumor effects, effectively preventing tumor growth. Our study provides an experimental basis for further optimizing the preparation of DC vaccines and reducing their costs.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 6","pages":"514-524"},"PeriodicalIF":5.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142727857","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 TULA-family proteins in T cells and autoimmune diseases TULA 家族蛋白在 T 细胞和自身免疫性疾病中的作用。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-18 DOI: 10.1038/s41435-024-00300-8

Hua Wang, Patrick Concannon, Yan Ge

{"title":"Roles of TULA-family proteins in T cells and autoimmune diseases","authors":"Hua Wang, Patrick Concannon, Yan Ge","doi":"10.1038/s41435-024-00300-8","DOIUrl":"10.1038/s41435-024-00300-8","url":null,"abstract":"The T cell Ubiquitin Ligand (TULA) protein family contains two members, UBASH3A and UBASH3B, that display similarities in protein sequence and domain structure. Both TULA proteins act to repress T cell activation via a combination of overlapping and nonredundant functions. UBASH3B acts mainly as a phosphatase that suppresses proximal T cell receptor (TCR) signaling. In contrast, UBASH3A acts primarily as an adaptor protein, interacting with other proteins (including UBASH3B) in T cells upon TCR stimulation and resulting in downregulation of TCR signaling and NF-κB signaling. Human genetic and functional studies have revealed another notable distinction between UBASH3A and UBASH3B: numerous genome-wide association studies have identified statistically significant associations between genetic variants in and around the UBASH3A gene and at least seven different autoimmune diseases, suggesting a key role of UBASH3A in autoimmunity. However, the evidence for an independent role of UBASH3B in autoimmune disease is limited. This review summarizes key findings regarding the roles of TULA proteins in T cell biology and autoimmunity, highlights the commonalities and differences between UBASH3A and UBASH3B, and speculates on the individual and joint effects of TULA proteins on T cell signaling.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 1","pages":"54-62"},"PeriodicalIF":5.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667225","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

Epigenetics behind CD8+ T cell activation and exhaustion CD8+ T 细胞活化和衰竭背后的表观遗传学。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-14 DOI: 10.1038/s41435-024-00307-1

Hao Zu, Xiaoqin Chen

引用次数: 0

Predictable regulation of gut microbiome in immunotherapeutic efficacy of gastric cancer 肠道微生物组对胃癌免疫治疗疗效的可预测调节。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-12 DOI: 10.1038/s41435-024-00306-2

Wei Gao, Xinli Wang, Yi Shi, Guangfeng Wu, Min Zhou, Xiaoyan Lin

{"title":"Predictable regulation of gut microbiome in immunotherapeutic efficacy of gastric cancer","authors":"Wei Gao, Xinli Wang, Yi Shi, Guangfeng Wu, Min Zhou, Xiaoyan Lin","doi":"10.1038/s41435-024-00306-2","DOIUrl":"10.1038/s41435-024-00306-2","url":null,"abstract":"Immunotherapy has showcased remarkable progress in the management of gastric cancer (GC), prompting the need to proactively identify and classify patients suitable for immunotherapy. Here, 30 patients were enrolled and stratified into three groups (PR, partial response; SD, stable disease; PD, progressive disease) based on efficacy assessment. 16S rRNA sequencing were performed to analyze the gut microbiome signature of patients at three timepoints. We found that immunotherapy interventions perturbed the gut microbiota of patients. Additionally, although differences at the enterotype level did not distinguish patients’ immunotherapy response, we identified 6, 7, and 19 species that were significantly enriched in PR, SD, and PD, respectively. Functional analysis showed that betalain biosynthesis and indole alkaloid biosynthesis were significantly different between the responders and non-responders. Furthermore, machine learning model utilizing only bacterial biomarkers accurately predicted immunotherapy efficacy with an Area Under the Curve (AUC) of 0.941. Notably, Akkermansia muciniphila and Dorea formicigenerans played a significant role in the classification of immunotherapy efficacy. In conclusion, our study reveals that gut microbiome signatures can be utilized as effective biomarkers for predicting the immunotherapy efficacy for GC.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 1","pages":"1-8"},"PeriodicalIF":5.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618624","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

Inorganic pyrophosphatase 1: a key player in immune and metabolic reprogramming in ankylosing spondylitis 无机焦磷酸酶 1：强直性脊柱炎免疫和代谢重编程的关键角色。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-07 DOI: 10.1038/s41435-024-00308-0

Tianyou Chen, Chengqian Huang, Jiarui Chen, Jiang Xue, Zhenwei Yang, Yihan Wang, Songze Wu, Wendi Wei, Liyi Chen, Shian Liao, Xiaopeng Qin, Rongqing He, Boli Qin, Chong Liu

{"title":"Inorganic pyrophosphatase 1: a key player in immune and metabolic reprogramming in ankylosing spondylitis","authors":"Tianyou Chen, Chengqian Huang, Jiarui Chen, Jiang Xue, Zhenwei Yang, Yihan Wang, Songze Wu, Wendi Wei, Liyi Chen, Shian Liao, Xiaopeng Qin, Rongqing He, Boli Qin, Chong Liu","doi":"10.1038/s41435-024-00308-0","DOIUrl":"10.1038/s41435-024-00308-0","url":null,"abstract":"The relationships among immune cells, metabolites, and AS events were analyzed via Mendelian randomization (MR), and potential immune cells and metabolites were identified as risk factors for AS. Their relationships were subjected to intermediary MR analysis to identify the final immune cells and metabolites. The vertebral bone marrow blood samples from three patients with and without AS were subjected to 10× single-cell sequencing to further elucidate the role of immune cells in AS. The key genes were screened via expression quantitative trait loci (eQTLs) and MR analyses. The metabolic differences between the two groups were compared through single-cell metabolism analysis. Two subgroups of differentiated (CD)8+ memory T cells and naive B cells were obtained from the combined results of intermediary MR analysis and AS single-cell analysis. After the verification of key genes, inorganic pyrophosphatase 1 (PPA1) was identified as the hub gene, as it is differentially expressed in CD8+ memory T cells and can affect the metabolism of T cells in AS by affecting the expression of ferulic acid (FA)4 sulfate, which participates in the cellular immunity in AS.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"26 1","pages":"9-21"},"PeriodicalIF":5.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604163","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

Regulatory T cells-related gene in primary sclerosing cholangitis: evidence from Mendelian randomization and transcriptome data 原发性硬化性胆管炎中的调节性 T 细胞相关基因：来自孟德尔随机化和转录组数据的证据。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-05 DOI: 10.1038/s41435-024-00304-4

Jianlan Hu, Youxing Wu, Danxia Zhang, Xiaoyang Wang, Yaohui Sheng, Hui Liao, Yangpeng Ou, Zhen Chen, Baolian Shu, Ruohu Gui

{"title":"Regulatory T cells-related gene in primary sclerosing cholangitis: evidence from Mendelian randomization and transcriptome data","authors":"Jianlan Hu, Youxing Wu, Danxia Zhang, Xiaoyang Wang, Yaohui Sheng, Hui Liao, Yangpeng Ou, Zhen Chen, Baolian Shu, Ruohu Gui","doi":"10.1038/s41435-024-00304-4","DOIUrl":"10.1038/s41435-024-00304-4","url":null,"abstract":"The present study utilized large-scale genome-wide association studies (GWAS) summary data (731 immune cell subtypes and three primary sclerosing cholangitis (PSC) GWAS datasets), meta-analysis, and two PSC transcriptome data to elucidate the pivotal role of Tregs proportion imbalance in the occurrence of PSC. Then, we employed weighted gene co-expression network analysis (WGCNA), differential analysis, and 107 combinations of 12 machine-learning algorithms to construct and validate an artificial intelligence-derived diagnostic model (Tregs classifier) according to the average area under curve (AUC) (0.959) in two cohorts. Quantitative real-time polymerase chain reaction (qRT-PCR) verified that compared to control, Akap10, Basp1, Dennd3, Plxnc1, and Tmco3 were significantly up-regulated in the PSC mice model yet the expression level of Klf13, and Scap was significantly lower. Furthermore, immune cell infiltration and functional enrichment analysis revealed significant associations of the hub Tregs-related gene with M2 macrophage, neutrophils, megakaryocyte-erythroid progenitor (MEP), natural killer T cell (NKT), and enrichment scores of the autophagic cell death, complement and coagulation cascades, metabolic disturbance, Fc gamma R-mediated phagocytosis, mitochondrial dysfunction, potentially mediating PSC onset. XGBoost algorithm and SHapley Additive exPlanations (SHAP) identified AKAP10 and KLF13 as optimal genes, which may be an important target for PSC.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 6","pages":"492-513"},"PeriodicalIF":5.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-024-00304-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575852","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