Genes and immunity最新文献

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":" ","pages":""},"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

{"title":"Epigenetics behind CD8+ T cell activation and exhaustion.","authors":"Hao Zu, Xiaoqin Chen","doi":"10.1038/s41435-024-00307-1","DOIUrl":"https://doi.org/10.1038/s41435-024-00307-1","url":null,"abstract":"CD8+ T cells play a critical role in specific immunity. In recent years, cell therapy has been emerging rapidly. The specific cytotoxic capabilities of these cells enable them to precisely identify and kill cells presenting specific antigens. This has demonstrated promise in the treatment of autoimmune diseases and cancers, with wide-ranging applications and value. However, in some diseases, such as tumors and chronic infections, T cells may adopt an exhausted phenotype, resulting in a loss of cytotoxicity and limiting their further application. Epigenetics plays a significant role in the differentiation and regulation of gene expression in cells. There is extensive evidence indicating that epigenetic remodeling plays an important role in T cell exhaustion. Therefore, further understanding its role in CD8+ T cell function can provide insights into the programmatic regulation of CD8+ T cells from a genetic perspective and overcome these diseases. We attempted to describe the relationship between the activation, function, and exhaustion mechanisms of CD8+ T cells, as well as epigenetics. This understanding makes it possible for us to address the aforementioned issues.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618619","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

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":"https://doi.org/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":" ","pages":""},"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":"https://doi.org/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":" ","pages":""},"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":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myeloid derived suppressor cells mediate hepatocyte proliferation and immune suppression during liver regeneration following resection. 髓系衍生抑制细胞在肝脏切除后的再生过程中介导肝细胞增殖和免疫抑制。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-02 DOI: 10.1038/s41435-024-00303-5

Ido Nachmany, Shir Nevo, Sarit Edelheit, Avital Sarusi-Portuguez, Gilgi Friedlander, Tomer-Meir Salame, Vera Pavlov, Oran Yakubovsky, Niv Pencovich

{"title":"Myeloid derived suppressor cells mediate hepatocyte proliferation and immune suppression during liver regeneration following resection.","authors":"Ido Nachmany, Shir Nevo, Sarit Edelheit, Avital Sarusi-Portuguez, Gilgi Friedlander, Tomer-Meir Salame, Vera Pavlov, Oran Yakubovsky, Niv Pencovich","doi":"10.1038/s41435-024-00303-5","DOIUrl":"https://doi.org/10.1038/s41435-024-00303-5","url":null,"abstract":"Liver regeneration following resection is a complex process relying on coordinated pathways and cell types in the remnant organ. Myeloid-Derived Suppressor Cells (MDSCs) have a role in liver regeneration-related angiogenesis but other roles they may play in this process remain to be elucidated. In this study, we sought to examine the effect of G-MDSCs on hepatocytes proliferation and immune modulation during liver regeneration. Global gene expression profiling of regenerating hepatocytes in mice with CD11b+Ly6G+ MDSCs (G-MDSCs) depletion revealed disrupted transcriptional progression from day one to day two after major liver resection. Key genes and pathways related to hepatocyte proliferation and immune response were differentially expressed upon MDSC depletion. Hepatocytes cellularity increased when co-cultured with G-MDSCs, or treated with amphiregulin, which G-MDSCs upregulate during regeneration. Cytometry by time-of-flight (CyTOF) analysis of the intra-liver immune milieu upon MDSC depletion during regeneration demonstrated increased natural killer cell proportions, alongside changes in other immune cell populations. Taken together, these results provide evidence that MDSCs contribute to early liver regeneration by promoting hepatocyte proliferation and modulating the intra-liver immune response, and illuminate the multifaceted role of MDSCs in liver regeneration.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564274","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 HLA-B -21 M/T dimorphism associates with disease severity in COVID-19. 在 COVID-19 中，HLA-B -21 M/T 二态性与疾病严重程度有关。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-01 DOI: 10.1038/s41435-024-00302-6

Benedikt Strunz, Pouria Momayyezi, Eleni Bilev, Jagadeeswara Rao Muvva, Puran Chen, Jonna Bister, Marie Schaffer, Mira Akber, Martin Cornillet, Amir Horowitz, Karl-Johan Malmberg, Olav Rooyackers, Soo Aleman, Hans-Gustaf Ljunggren, Niklas K Björkström, Kristoffer Strålin, Quirin Hammer

{"title":"The HLA-B -21 M/T dimorphism associates with disease severity in COVID-19.","authors":"Benedikt Strunz, Pouria Momayyezi, Eleni Bilev, Jagadeeswara Rao Muvva, Puran Chen, Jonna Bister, Marie Schaffer, Mira Akber, Martin Cornillet, Amir Horowitz, Karl-Johan Malmberg, Olav Rooyackers, Soo Aleman, Hans-Gustaf Ljunggren, Niklas K Björkström, Kristoffer Strålin, Quirin Hammer","doi":"10.1038/s41435-024-00302-6","DOIUrl":"https://doi.org/10.1038/s41435-024-00302-6","url":null,"abstract":"Host genetics shape immune responses and influence severity of infectious diseases. The HLA-B -21 M/T dimorphism tunes the functionality of natural killer (NK) cells expressing the inhibitory receptor NKG2A. NKG2A+ NK cells have been reported to recognize SARS-CoV-2-infected cells, but it remains unclear whether the HLA-B -21 M/T dimorphism associates with COVID-19 severity. Here, we investigated the influence of the HLA-B -21 M/T dimorphism in a cohort of 230 unvaccinated patients hospitalized with COVID-19 and requiring respiratory support. We found that HLA-B -21 M/M genotypes were more prevalent in patients with moderate compared to severe COVID-19 (6.0% vs. 0.9%). Comparison of age- and sex-matched sub-groups revealed that patients with M/M genotypes required mechanical respiratory support less frequently (OR = 0.13, 95% CI = 0.01-0.76, P = 0.013). Furthermore, patients with M/M genotypes showed a coordinately shifted signature of clinical laboratory parameters, coinciding with elevated serum levels of the anti-viral cytokine IFN-γ. These findings demonstrate that HLA-B variants associate with COVID-19 severity and suggest that the robust functionality of NKG2A+ NK cells in patients carrying the M/M genotype may contribute to protection from severe disease.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564281","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

Correction: LncRNA sequencing reveals an essential role for the lncRNA-mediated ceRNA network in penile squamous cell carcinoma. 更正：LncRNA测序揭示了lncRNA介导的ceRNA网络在阴茎鳞状细胞癌中的重要作用。

IF 5 3区医学

Genes and immunity Pub Date : 2024-10-29 DOI: 10.1038/s41435-024-00301-7

Jian Cao, Lin Du, Xueheng Zhao, Zhizhong Liu, Junbin Yuan, Yanwei Luo, Shanshan Zhang, Zailong Qin, Jie Guo

引用次数: 0

The conundrum of CD8+ T cell trajectories in low antigenic tumors: How to overcome a hypofunctional state distinct from antigen-driven exhaustion? 低抗原肿瘤中 CD8+ T 细胞轨迹的难题：如何克服不同于抗原驱动衰竭的低功能状态？

IF 5 3区医学

Genes and immunity Pub Date : 2024-10-09 DOI: 10.1038/s41435-024-00299-y

Angeliki Datsi, Rüdiger V. Sorg, Abhishek D. Garg

引用次数: 0

A potential coagulation-related diagnostic model associated with immune infiltration for acute myocardial infarction. 与急性心肌梗塞免疫浸润相关的潜在凝血相关诊断模型。

IF 5 3区医学

Genes and immunity Pub Date : 2024-10-08 DOI: 10.1038/s41435-024-00298-z

Guoqing Liu, Wang Liao, Xiangwen Lv, Lifeng Huang, Min He, Lang Li

{"title":"A potential coagulation-related diagnostic model associated with immune infiltration for acute myocardial infarction.","authors":"Guoqing Liu, Wang Liao, Xiangwen Lv, Lifeng Huang, Min He, Lang Li","doi":"10.1038/s41435-024-00298-z","DOIUrl":"https://doi.org/10.1038/s41435-024-00298-z","url":null,"abstract":"The production of pro-coagulation factors can affect the development and prognosis of acute myocardial infarction (AMI). The clinical value of coagulation-related genes (CRGs) was investigated to discover new targets for diagnosing and treating AMI. We screened 335 differentially expressed genes (DEGs) between AMI and healthy individuals based on the GSE66360 dataset. We took the intersection of the obtained DEGs with 139 CRGs. Finally, 10 differentially expressed CEGs were screened out. The random forest algorithm was constructed to identify 6 signature CRGs (THBS1, SERPINA1, THBD, MMP9, MAFF, and PLAU). Subsequently, the established predictive model was found to have good diagnostic accuracy (AUC = 0.9694 in the training cohort [GSE66360 dataset] and 0.9076 in the external validation cohort [GSE48060 dataset]). Consensus clustering identified the CRG clusters, and the accuracy of the grouping was verified. We found that AMI patients can be divided into two distinct subgroups based on the differentially expressed CRGs. Immune cell infiltration level was consistent with the expression levels of CRGs based on single sample gene set enrichment analysis. These findings reveal the potential role of CRGs in AMI. Characterizing the coagulation features of AMI patients can help in the risk stratification of patients and provide personalized treatment strategies.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389808","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