Pub Date : 2024-08-05DOI: 10.1038/s41435-024-00290-7
Meng-Qi Shen, Qian Guo, Wei Li, Zhong-Ming Qian
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.
载脂蛋白 E（ApoE）在体内铁平衡中起着至关重要的作用，而巨噬细胞是哺乳动物体内负责处理铁的主要细胞。然而，载脂蛋白 E 是否会影响脾脏巨噬细胞（SM）的功能亚型和铁处理能力尚不清楚。在这里，我们研究了载脂蛋白E缺乏（ApoE-/-）对脾巨噬细胞极化和铁含量的影响及其潜在机制。研究发现，载脂蛋白E-/-诱导28周龄小鼠脾脏巨噬细胞中M1标记基因CD86、IL-1β、IL-6、IL-12、TNF-α和iNOS的表达显著增加，M2标记基因CD206、Arg-1、IL-10和Ym-1的表达减少、同时，ApoE-/-导致28周龄小鼠脾脏和/或SM中铁含量和铁蛋白、转铁蛋白受体1（TfR1）、铁调节蛋白1（IRP1）和血红素加氧酶1（HO-1）的表达显著增加，铁蛋白1（Fpn1）减少。结论是载脂蛋白E-/-可通过TfR/IRPs介导的铁摄取增加和Fpn1介导的铁释放减少来增加铁含量，从而导致SM极化为M1表型。
{"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}
Pub Date : 2024-07-29DOI: 10.1038/s41435-024-00289-0
Qingyu Cheng, Weidong Zhao, Xiaoyuan Song, Tengchuan Jin
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.
{"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}
Pub Date : 2024-07-29DOI: 10.1038/s41435-024-00287-2
Bo Cai, Yibin Huang, Dandan Liu, Yizheng You, Nuoshi Chen, Ligang Jie, Hongyan Du
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.
与健康人群相比，类风湿性关节炎（RA）患者罹患肺癌的风险较高。然而，有关 RA 与肺腺癌（LUAD）之间关系的研究很少，尤其是基因层面的机制。在这项研究中，我们调查了RA与肺腺癌之间有关铁突变相关基因的联系。我们从基因表达总库（GEO）中获得了RA（GSE77298和GSE82107）和LUAD（GSE75037）的RNA-seq数据。从网站（ http://www.zhounan.org/ferrdb/ ）上获得了 259 个铁变态反应相关基因。将从 RA 和 LUAD 数据集中获得的差异基因与铁变态反应相关基因进行交叉，得到了铁变态反应相关差异表达基因（FRDEGs）。接着，构建 mRNA-miRNA 网络，然后对目标基因进行基因组富集分析（Gene Set Enrichment Analysis，GSEA）。CIBERSORT 算法用于分析免疫浸润。最后，利用外部数据集（GSE89408 和 GSE48780）和癌症基因组图谱（TCGA）数据集对结果进行了验证。我们获得了 LUAD 和 RA 的共同 FRDEGs：FANCD2、HELLS、RRM2、G6PD、VLDLR。这五个基因在 RA 和 LUAD 的进展过程中起着重要作用。它们对这两种疾病也具有重要的诊断价值。此外，我们还发现 LUAD 和 RA 有共同的信号通路和相似的免疫机制。
{"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}
Pub Date : 2024-07-25DOI: 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
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.
{"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}
Pub Date : 2024-07-09DOI: 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
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.
败血症和侵袭性真菌病（IFD）等感染事件对急性髓性白血病（AML）患者构成重大风险。包括我们自己在内的以往研究表明，先天性免疫系统中的单核苷酸多态性（SNPs）在影响个体感染易感性方面具有潜在作用。然而，其中许多关联缺乏独立队列的验证。本研究试图在一个独立的患者队列中验证 6 个基因（TLR2、TLR4、Dectin-1、DC-SIGN、PTX3、L-Ficolin）中 11 个候选 SNPs 的影响。对接受强化诱导化疗的新诊断急性髓细胞白血病患者的两个队列进行了分析：一个是由 186 名患者组成的分层队列，另一个是由 138 名患者组成的验证队列。发现每个队列中的多个 SNP 与感染并发症有关，尤其是 DC-SIGN SNP rs4804800 与两个队列中的败血症均有显著关联。在一个队列中，PTX3 和 Dectin-1 基因中的 SNP 与 IFD 的发生有关。这项研究是首次验证与强化诱导化疗后急性髓细胞白血病患者感染事件相关的候选基因。确定感染的遗传倾向可能会对 AML 患者的抗菌预防和治疗管理产生重大影响。
{"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}
Pub Date : 2024-06-26DOI: 10.1038/s41435-024-00284-5
Emma Beaumont, Michaela Müller-Trutwin, Nicolas Huot
{"title":"SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells","authors":"Emma Beaumont, Michaela Müller-Trutwin, Nicolas Huot","doi":"10.1038/s41435-024-00284-5","DOIUrl":"10.1038/s41435-024-00284-5","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 5","pages":"443-445"},"PeriodicalIF":5.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456317","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}
Pub Date : 2024-06-22DOI: 10.1038/s41435-024-00283-6
Peter Artimovič, Ivana Špaková, Ema Macejková, Timea Pribulová, Miroslava Rabajdová, Mária Mareková, Martina Zavacká
MicroRNAs play a crucial role in regulating the immune responses induced by ischemia/reperfusion injury. Through their ability to modulate gene expression, microRNAs adjust immune responses by targeting specific genes and signaling pathways. This review focuses on the impact of microRNAs on the inflammatory pathways triggered during ischemia/reperfusion injury and highlights their ability to modulate inflammation, playing a critical role in the pathophysiology of ischemia/reperfusion injury. Dysregulated expression of microRNAs contributes to the pathogenesis of ischemia/reperfusion injury, therefore targeting specific microRNAs offers an opportunity to restore immune homeostasis and improve patient outcomes. Understanding the complex network of immunoregulatory microRNAs could provide novel therapeutic interventions aimed at attenuating excessive inflammation and preserving tissue integrity.
{"title":"The ability of microRNAs to regulate the immune response in ischemia/reperfusion inflammatory pathways","authors":"Peter Artimovič, Ivana Špaková, Ema Macejková, Timea Pribulová, Miroslava Rabajdová, Mária Mareková, Martina Zavacká","doi":"10.1038/s41435-024-00283-6","DOIUrl":"10.1038/s41435-024-00283-6","url":null,"abstract":"MicroRNAs play a crucial role in regulating the immune responses induced by ischemia/reperfusion injury. Through their ability to modulate gene expression, microRNAs adjust immune responses by targeting specific genes and signaling pathways. This review focuses on the impact of microRNAs on the inflammatory pathways triggered during ischemia/reperfusion injury and highlights their ability to modulate inflammation, playing a critical role in the pathophysiology of ischemia/reperfusion injury. Dysregulated expression of microRNAs contributes to the pathogenesis of ischemia/reperfusion injury, therefore targeting specific microRNAs offers an opportunity to restore immune homeostasis and improve patient outcomes. Understanding the complex network of immunoregulatory microRNAs could provide novel therapeutic interventions aimed at attenuating excessive inflammation and preserving tissue integrity.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 4","pages":"277-296"},"PeriodicalIF":5.0,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-024-00283-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440409","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}
Pub Date : 2024-06-19DOI: 10.1038/s41435-024-00282-7
Teresa Neuwirth, Azuah L. Gonzalez, Emilie Fisher-Gupta, Georg Stary
{"title":"Correction: Getting under the skin: resident memory CD8+ T cells have a second residence in the draining lymph node","authors":"Teresa Neuwirth, Azuah L. Gonzalez, Emilie Fisher-Gupta, Georg Stary","doi":"10.1038/s41435-024-00282-7","DOIUrl":"10.1038/s41435-024-00282-7","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 4","pages":"351-351"},"PeriodicalIF":5.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-024-00282-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426694","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}
Pub Date : 2024-06-12DOI: 10.1038/s41435-024-00280-9
Yu Chen, Xudong Fan, Ruohuang Lu, Shan Zeng, Pingping Gan
Gallbladder cancer (GBC) is an aggressive cancer with poor prognosis. PARP inhibitors (PARPi) target PARP enzymes and have shown efficacy in patients with breast cancer gene (BRCA) mutations. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has transformed cancer treatment. However, the combined impact of PARPi and ICIs in GBC remains unclear. We present a groundbreaking case of a GBC patient with BRCA2 mutations who received combination therapy with PARPi and ICIs after failing multiple lines of treatment. Next-generation sequencing (NGS-Seq) identified BRCA gene mutations. To further investigate potential mechanisms, we developed a PARP1-BRCA1-BRCA2 pathway-related risk score (PBscore) system to evaluate the impact of PARPi on the tumor immune microenvironment via RNA-Seq data. Gene expression and functional analysis identified potential mechanisms associated with the PBscore. Experimental validation assessed the impact of the combination therapy on the tumor microenvironment using multiplexed immunofluorescence imaging and immunohistochemistry in patients with BRCA gene wild type or mutations. RNA-Seq analysis revealed correlations between PBscore, immune checkpoint levels, tumor-infiltrating immune cells (TIICs), and the cancer-immunity cycle. Multiplexed immunofluorescence imaging validated that low PBscore patients might have an active tumor microenvironment. Furthermore, upon drug resistance, we observed an upregulation of negative immune checkpoints such as CEACAM1, indicating that the tumor immune microenvironment becomes suppressed after resistance. Our study revealed that PBscore could serve as a biomarker to predict immunotherapy efficacy, offering a promising alternative for BRCA2-mutated GBC patients.
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