Pub Date : 2023-11-01DOI: 10.1016/j.imbio.2023.152762
Marion Vanharen, Denis Girard
It is well established that some differences exist between the male and female immune systems. Despites this, a sex-based analysis is not frequently performed in most scientific published reports. Knowing that inflammation is a common undesired effect observed resulting from nanoparticle (NP) exposure, we investigate here how in vitro treatment of gold NPs with a primary size of 20 and 70 nm (AuNP20 and AuNP70, respectively) will alter the biology of human eosinophils isolated from men and women blood. We found that treatment of AuNP70, but not AuNP20, significantly delay apoptosis only in eosinophils isolated from women. AuNPs were found to decrease eosinophil phagocytosis, however, significance was only observed in AuNP20-induced eosinophils isolated from women. The production of IL-8 was significantly increased in response to both AuNPs but only in eosinophils isolated from men and the production of IL-1β was increased in AuNPs-induced eosinophils, although significance was observed only in AuNP70-induced eosinophils isolated from women. We conclude that future studies investigating the toxicity of AuNPs (or other NPs) should include a sex-based analysis, especially if the tested NPs have potential medical applications knowing the increased interest in the development of personalized precision medicine.
{"title":"Impact of gold nanoparticles (AuNPs) on eosinophils isolated from male and female individuals","authors":"Marion Vanharen, Denis Girard","doi":"10.1016/j.imbio.2023.152762","DOIUrl":"https://doi.org/10.1016/j.imbio.2023.152762","url":null,"abstract":"<div><p><span>It is well established that some differences exist between the male and female immune systems. Despites this, a sex-based analysis is not frequently performed in most scientific published reports. Knowing that inflammation is a common undesired effect observed resulting from nanoparticle<span> (NP) exposure, we investigate here how in vitro treatment<span> of gold NPs with a primary size of 20 and 70 nm (AuNP</span></span></span><sub>20</sub> and AuNP<sub>70</sub><span>, respectively) will alter the biology of human eosinophils isolated from men and women blood. We found that treatment of AuNP</span><sub>70</sub>, but not AuNP<sub>20</sub><span><span>, significantly delay apoptosis only in eosinophils isolated from women. AuNPs were found to decrease eosinophil </span>phagocytosis, however, significance was only observed in AuNP</span><sub>20</sub>-induced eosinophils isolated from women. The production of IL-8 was significantly increased in response to both AuNPs but only in eosinophils isolated from men and the production of IL-1β was increased in AuNPs-induced eosinophils, although significance was observed only in AuNP<sub>70</sub>-induced eosinophils isolated from women. We conclude that future studies investigating the toxicity of AuNPs (or other NPs) should include a sex-based analysis, especially if the tested NPs have potential medical applications knowing the increased interest in the development of personalized precision medicine.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138435932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-05DOI: 10.1016/j.imbio.2023.152753
Wendian Xiong , Lei Jia , Yanfei Cai , Yun Chen , Mingzhu Gao , Jian Jin , Jingyu Zhu
Phosphatidylinositol 3-kinase delta (PI3Kδ) and gamma (PI3Kγ) are predominantly located in immune and hematopoietic cells. It is well-established that PI3Kδ/γ plays important roles in the immune system and participates in inflammation; hence, it could be a potential target for anti-inflammatory therapy. Currently, several PI3K inhibitors are used clinically to treat cancers with aberrant PI3K signaling; however, their role in treating acute respiratory inflammatory diseases has rarely been explored. Herein, we investigated the potential anti-inflammatory activities of several pharmacological PI3K inhibitors, including marketed drugs idelalisib (PI3Kδ), duvelisib (PI3Kδ/γ), and copanlisib (pan-PI3K with preferential α/δ) and the clinical drug eganelisib (PI3Kγ), for treating acute lung injury (ALI). In the lipopolysaccharide-induced RAW264.7 macrophage inflammatory model, the four inhibitors significantly suppressed proinflammatory cytokine expression by inhibiting the PI3K signaling pathway. Oral administration of PI3K inhibitors markedly improved lung injury in a murine model of ALI. PI3K pathway inhibition decreased inflammatory cell infiltration and total protein levels, as well as reduced the expression of associated lung inflammatory factors. Collectively, all four representative PI3K inhibitors exerted prominent anti-inflammatory properties, indicating that PI3K δ and/or γ inhibition could be ideal targets to treat respiratory inflammatory diseases by reducing the inflammatory response. The findings of the current study provide a new basis for utilizing PI3K inhibitors to treat acute respiratory inflammatory diseases.
{"title":"Evaluation of the anti-inflammatory effects of PI3Kδ/γ inhibitors for treating acute lung injury","authors":"Wendian Xiong , Lei Jia , Yanfei Cai , Yun Chen , Mingzhu Gao , Jian Jin , Jingyu Zhu","doi":"10.1016/j.imbio.2023.152753","DOIUrl":"10.1016/j.imbio.2023.152753","url":null,"abstract":"<div><p>Phosphatidylinositol 3-kinase delta (PI3Kδ) and gamma (PI3Kγ) are predominantly located in immune and hematopoietic cells. It is well-established that PI3Kδ/γ plays important roles in the immune system and participates in inflammation; hence, it could be a potential target for anti-inflammatory therapy. Currently, several PI3K inhibitors are used clinically to treat cancers with aberrant PI3K signaling; however, their role in treating acute respiratory inflammatory diseases has rarely been explored. Herein, we investigated the potential anti-inflammatory activities of several pharmacological PI3K inhibitors, including marketed drugs idelalisib (PI3Kδ), duvelisib (PI3Kδ/γ), and copanlisib (pan-PI3K with preferential α/δ) and the clinical drug eganelisib (PI3Kγ), for treating acute lung injury (ALI). In the lipopolysaccharide-induced RAW264.7 macrophage inflammatory model, the four inhibitors significantly suppressed proinflammatory cytokine expression by inhibiting the PI3K signaling pathway. Oral administration of PI3K inhibitors markedly improved lung injury in a murine model of ALI. PI3K pathway inhibition decreased inflammatory cell infiltration and total<!--> <!-->protein levels, as well as reduced the expression of associated lung inflammatory factors. Collectively, all four representative PI3K inhibitors exerted prominent anti-inflammatory properties, indicating that PI3K δ and/or γ inhibition could be ideal targets to treat respiratory inflammatory diseases by reducing the inflammatory response. The findings of the current study provide a new basis for utilizing PI3K inhibitors to treat acute respiratory inflammatory diseases.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41199496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-04DOI: 10.1016/j.imbio.2023.152754
Xiaofeng Liang , Zhishen Peng , Ying Deng , Xiaobing Lin , Runnan Chen , Yujing Niu , Weiyi Lin , Zien Lin , Kuan Lai , Shanshan Wei
Psoriasis and inflammatory bowel disease (IBD) have a similar etiology, including abnormal activation of T cells. Differentially expressed genes (DEGs) analysis was used to search for shared genes. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis were then performed. Secondly, single-cell RNA analysis (scRNA-seq) and immune infiltration were employed to explore the immune imbalance of the diseases. By weighted gene co expression network analysis (WGCNA), we obtained hub shared genes. Furthermore, we analyzed the diagnostic performance and immune association with the hub genes. Finally, functional enrichment of miRNAs related to hub shared genes was carried out. Single-cell analysis showed a high proportion of T cells among infiltrated immune cells and immune infiltration showed CD4+ T and γδ T cells were significantly elevated in diseases. Hub shared genes, LCN2, CXCL1 and PI3 had excellent diagnostic properties and were positively correlated with neutrophils, CD4+ T and γδ T cells. IL17 and TNF signaling pathway were the common pathway. In conclusion, CD4+ and γδ T cells and hub shared genes may play a crucial part in common mechanism between psoriasis and IBD. Moreover, hub shared genes may be potential diagnostic markers.
{"title":"The role of T cells and shared genes in psoriasis and inflammatory bowel disease based on single-cell RNA and comprehensive analysis","authors":"Xiaofeng Liang , Zhishen Peng , Ying Deng , Xiaobing Lin , Runnan Chen , Yujing Niu , Weiyi Lin , Zien Lin , Kuan Lai , Shanshan Wei","doi":"10.1016/j.imbio.2023.152754","DOIUrl":"10.1016/j.imbio.2023.152754","url":null,"abstract":"<div><p>Psoriasis and inflammatory bowel disease (IBD) have a similar etiology, including abnormal activation of T cells. Differentially expressed genes (DEGs) analysis was used to search for shared genes. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis were then performed. Secondly, single-cell RNA analysis (scRNA-seq) and immune infiltration were employed to explore the immune imbalance of the diseases. By weighted gene co expression network analysis (WGCNA), we obtained hub shared genes. Furthermore, we analyzed the diagnostic performance and immune association with the hub genes. Finally, functional enrichment of miRNAs related to hub shared genes was carried out. Single-cell analysis showed a high proportion of T cells among infiltrated immune cells and immune infiltration showed CD4<sup>+</sup> T and γδ T cells were significantly elevated in diseases. Hub shared genes, LCN2, CXCL1 and PI3 had excellent diagnostic properties and were positively correlated with neutrophils, CD4<sup>+</sup> T and γδ T cells. IL17 and TNF signaling pathway were the common pathway. In conclusion, CD4<sup>+</sup> and γδ T cells and hub shared genes may play a crucial part in common mechanism between psoriasis and IBD. Moreover, hub shared genes may be potential diagnostic markers.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-02DOI: 10.1016/j.imbio.2023.152752
Paula Arbildi , Federico Calvo , Victoria Macías , Claudio Rodríguez-Camejo , Cecilia Sóñora , Ana Hernández
Tissue transglutaminase (TG2) expressed in monocytes and macrophage is known to participate in processes during either early and resolution stages of inflammation. The alternative splicing of tissue transglutaminase gene is a mechanism that increases its functional diversity. Four spliced variants are known with truncated C-terminal domains (TGM2_v2, TGM2_v3, TGM2_v4a, TGM2_v4b) but scarce information is available about its expression in human monocyte and macrophages.
We studied the expression of canonical TG2 (TGM2_v1) and its short spliced variants by RT-PCR during differentiation of TPH-1 derived macrophages (dTHP-1) using two protocols (condition I and II) that differ in Phorbol-12-myristate-13-acetate dose and time schedule. The production of TNF-α and IL-1β in supernatant of dTHP-1, measured by ELISA in supernatants showed higher proinflammatory milieu in condition I.
We found that the expression of all mRNA TG2 spliced variants were up-regulated during macrophage differentiation and after IFN-γ treatment of dTHP-1 cells in both conditions. Nevertheless, the relative fold increase or TGM2_v3 in relation with TGM2_v1 was higher only with the condition I.
M1/M2-like THP-1 macrophages obtained with IFN-γ/IL-4 treatments showed that the up-regulation of TGM2_v1 induced by IL-4 was higher in relation with any short spliced variants. The qualitative profile of relative contribution of spliced variants in M1/M2-like THP-1 cells showed a trend to higher expression of TGM2_v3 in the inflammatory functional phenotype.
Our results contribute to the knowledge about TG2 spliced variants in the biology of monocyte/macrophage cells and show how the differentiation conditions can alter their expression and cell function.
{"title":"Study of tissue transglutaminase spliced variants expressed in THP-1 derived macrophages exhibiting distinct functional phenotypes","authors":"Paula Arbildi , Federico Calvo , Victoria Macías , Claudio Rodríguez-Camejo , Cecilia Sóñora , Ana Hernández","doi":"10.1016/j.imbio.2023.152752","DOIUrl":"10.1016/j.imbio.2023.152752","url":null,"abstract":"<div><p>Tissue transglutaminase (TG2) expressed in monocytes and macrophage is known to participate in processes during either early and resolution stages of inflammation. The alternative splicing of tissue transglutaminase gene is a mechanism that increases its functional diversity. Four spliced variants are known with truncated C-terminal domains (TGM2_v2, TGM2_v3, TGM2_v4a, TGM2_v4b) but scarce information is available about its expression in human monocyte and macrophages.</p><p>We studied the expression of canonical TG2 (TGM2_v1) and its short spliced variants by RT-PCR during differentiation of TPH-1 derived macrophages (dTHP-1) using two protocols (condition I and II) that differ in Phorbol-12-myristate-13-acetate dose and time schedule. The production of TNF-α and IL-1β in supernatant of dTHP-1, measured by ELISA in supernatants showed higher proinflammatory milieu in condition I.</p><p>We found that the expression of all mRNA TG2 spliced variants were up-regulated during macrophage differentiation and after IFN-γ treatment of dTHP-1 cells in both conditions. Nevertheless, the relative fold increase or TGM2_v3 in relation with TGM2_v1 was higher only with the condition I.</p><p>M1/M2-like THP-1 macrophages obtained with IFN-γ/IL-4 treatments showed that the up-regulation of TGM2_v1 induced by IL-4 was higher in relation with any short spliced variants. The qualitative profile of relative contribution of spliced variants in M1/M2-like THP-1 cells showed a trend to higher expression of TGM2_v3 in the inflammatory functional phenotype.</p><p>Our results contribute to the knowledge about TG2 spliced variants in the biology of monocyte/macrophage cells and show how the differentiation conditions can alter their expression and cell function.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-26DOI: 10.1016/j.imbio.2023.152750
Yang Gao , Xuan Tang , Guanghui Qian , Hongbiao Huang , Nana Wang , Yan Wang , Wenyu Zhuo , Jiaqi Jiang , Yiming Zheng , Wenjie Li , Zhiheng Liu , Xuan Li , Lei Xu , Jiaying Zhang , Li Huang , Ying Liu , Haitao Lv
Background
Kawasaki disease (KD) is a systemic vasculitis that commonly affects children and its etiology remains unknown. Growing evidence suggests that immune-mediated inflammation and immune cells in the peripheral blood play crucial roles in the pathophysiology of KD. The objective of this research was to find important biomarkers and immune-related mechanisms implicated in KD, along with their correlation with immune cells in the peripheral blood.
Material/Methods
Gene microarray data from the Gene Expression Omnibus (GEO) was utilized in this study. Three datasets, namely GSE63881 (341 samples), GSE73463 (233 samples), and GSE73461 (279 samples), were obtained. To find intersecting genes, we employed differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA). Subsequently, functional annotation, construction of protein–protein interaction (PPI) networks, and Least Absolute Shrinkage and Selection Operator (LASSO) regression were performed to identify hub genes. The accuracy of these hub genes in identifying KD was evaluated using the receiver operating characteristic curve (ROC). Furthermore, Gene Set Variation Analysis (GSVA) was employed to explore the composition of circulating immune cells within the assessed datasets and their relationship with the hub gene markers.
Results
WGCNA yielded eight co-expression modules, with one hub module (MEblue module) exhibiting the strongest association with acute KD. 425 distinct genes were identified. Integrating WGCNA and DEGs yielded a total of 277 intersecting genes. By conducting LASSO analysis, five hub genes (S100A12, MMP9, TLR2, NLRC4 and ARG1) were identified as potential biomarkers for KD. The diagnostic value of these five hub genes was demonstrated through ROC curve analysis, indicating their high accuracy in diagnosing KD. Analysis of the circulating immune cell composition within the assessed datasets revealed a significant association between KD and various immune cell types, including activated dendritic cells, neutrophils, immature dendritic cells, macrophages, and activated CD8 T cells. Importantly, all five hub genes exhibited strong correlations with immune cells.
Conclusion
Activated dendritic cells, neutrophils, and macrophages were closely associated with the pathogenesis of KD. Furthermore, the hub genes (S100A12, MMP9, TLR2, NLRC4, and ARG1) are likely to participate in the pathogenic mechanisms of KD through immune-related signaling pathways.
{"title":"Identification of hub biomarkers and immune-related pathways participating in the progression of Kawasaki disease by integrated bioinformatics analysis","authors":"Yang Gao , Xuan Tang , Guanghui Qian , Hongbiao Huang , Nana Wang , Yan Wang , Wenyu Zhuo , Jiaqi Jiang , Yiming Zheng , Wenjie Li , Zhiheng Liu , Xuan Li , Lei Xu , Jiaying Zhang , Li Huang , Ying Liu , Haitao Lv","doi":"10.1016/j.imbio.2023.152750","DOIUrl":"10.1016/j.imbio.2023.152750","url":null,"abstract":"<div><h3>Background</h3><p>Kawasaki disease (KD) is a systemic vasculitis that commonly affects children and its etiology remains unknown. Growing evidence suggests that immune-mediated inflammation and immune cells in the peripheral blood play crucial roles in the pathophysiology of KD. The objective of this research was to find important biomarkers and immune-related mechanisms implicated in KD, along with their correlation with immune cells in the peripheral blood.</p></div><div><h3>Material/Methods</h3><p>Gene microarray data from the Gene Expression Omnibus (GEO) was utilized in this study. Three datasets, namely GSE63881 (341 samples), GSE73463 (233 samples), and GSE73461 (279 samples), were obtained. To find intersecting genes, we employed differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA). Subsequently, functional annotation, construction of protein–protein interaction (PPI) networks, and Least Absolute Shrinkage and Selection Operator (LASSO) regression were performed to identify hub genes. The accuracy of these hub genes in identifying KD was evaluated using the receiver operating characteristic curve (ROC). Furthermore, Gene Set Variation Analysis (GSVA) was employed to explore the composition of circulating immune cells within the assessed datasets and their relationship with the hub gene markers.</p></div><div><h3>Results</h3><p>WGCNA yielded eight co-expression modules, with one hub module (MEblue module) exhibiting the strongest association with acute KD. 425 distinct genes were identified. Integrating WGCNA and DEGs yielded a total of 277 intersecting genes. By conducting LASSO analysis, five hub genes (S100A12, MMP9, TLR2, NLRC4 and ARG1) were identified as potential biomarkers for KD. The diagnostic value of these five hub genes was demonstrated through ROC curve analysis, indicating their high accuracy in diagnosing KD. Analysis of the circulating immune cell composition within the assessed datasets revealed a significant association between KD and various immune cell types, including activated dendritic cells, neutrophils, immature dendritic cells, macrophages, and activated CD8 T cells. Importantly, all five hub genes exhibited strong correlations with immune cells.</p></div><div><h3>Conclusion</h3><p>Activated dendritic cells, neutrophils, and macrophages were closely associated with the pathogenesis of KD. Furthermore, the hub genes (S100A12, MMP9, TLR2, NLRC4, and ARG1) are likely to participate in the pathogenic mechanisms of KD through immune-related signaling pathways.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41199497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-23DOI: 10.1016/j.imbio.2023.152751
Chenghu Song , Weici Liu , Guanyu Jiang , Zhao He , Ruixin Wang , Xiaokun Wang , Ruo Chen , Wenjun Mao , Shaojin Zhu
Background
The prevalence and fatality rates of lung cancer are experiencing a rapid escalation. Natural Killer (NK) cells have been established to have a crucial role in both tumor initiation and progression. Nevertheless, uncertainties persist regarding their precise implications in the prognosis of LUAD.
Methods
The data were obtained from reputable sources, such as the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) database, and our internally generated sequencing data. Utilizing the TCGA data as a background, we selected intersecting genes, validated by cluster analysis, to establish a Cox model and validated it using the GEO datasets. Furthermore, we conducted extensive analyses to investigate the significance of potential biomarkers in relation to immune cell infiltration, single-cell data, differential gene expression, and drug sensitivity.
Results
67 immune-related genes associated with NK cells (NK-IRGs) were identified in the TCGA datasets, whose research potential was demonstrated by cluster analysis. A prognostic signature was identified utilizing the univariate and multivariate Cox model, resulting in the identification of five genes, which was validated using GEO datasets. Additionally, the nomogram's calibration curve demonstrated exceptional concordance between the projected and actual survival rates. Subsequent investigations uncovered that this prognostic signature demonstrated its independence as a risk factor. Notably, in the low-risk group, NK cells exhibited elevated levels of immune checkpoint molecules, indicating heightened sensitivity to immune therapy. These findings highlight the potential of utilizing this signature as a valuable tool in the selection of patients who could benefit from targeted immune interventions.
{"title":"Identification and validation of a novel NK cells-related signature to predict prognosis and immune microenvironment in LUAD","authors":"Chenghu Song , Weici Liu , Guanyu Jiang , Zhao He , Ruixin Wang , Xiaokun Wang , Ruo Chen , Wenjun Mao , Shaojin Zhu","doi":"10.1016/j.imbio.2023.152751","DOIUrl":"10.1016/j.imbio.2023.152751","url":null,"abstract":"<div><h3>Background</h3><p>The prevalence and fatality rates of lung cancer are experiencing a rapid escalation. Natural Killer (NK) cells have been established to have a crucial role in both tumor initiation and progression. Nevertheless, uncertainties persist regarding their precise implications in the prognosis of LUAD.</p></div><div><h3>Methods</h3><p><span>The data were obtained from reputable sources, such as the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) database, and our internally generated sequencing data. Utilizing the TCGA data as a background, we selected intersecting genes, validated by cluster analysis, to establish a Cox model and validated it using the GEO datasets. Furthermore, we conducted extensive analyses to investigate the significance of potential biomarkers in relation to </span>immune cell<span> infiltration, single-cell data, differential gene expression, and drug sensitivity.</span></p></div><div><h3>Results</h3><p>67 immune-related genes associated with NK cells (NK-IRGs) were identified in the TCGA datasets, whose research potential was demonstrated by cluster analysis. A prognostic signature was identified utilizing the univariate and multivariate Cox model, resulting in the identification of five genes, which was validated using GEO datasets. Additionally, the nomogram's calibration curve demonstrated exceptional concordance between the projected and actual survival rates. Subsequent investigations uncovered that this prognostic signature demonstrated its independence as a risk factor. Notably, in the low-risk group, NK cells exhibited elevated levels of immune checkpoint molecules, indicating heightened sensitivity to immune therapy. These findings highlight the potential of utilizing this signature as a valuable tool in the selection of patients who could benefit from targeted immune interventions.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41151928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-22DOI: 10.1016/j.imbio.2023.152749
Yiming Zhao , Ming Zhao , Meng Li , Xiancan Ma , Mohan Zheng , Yuying Nie , Yaoyi Zhu , Jiaxin Ren , Ainizati Hasimu , Zihang Yuan , Qi Li , Ayibaota Bahabayi , Zhonghui Zhang , Xingyue Zeng , Chen Liu
Objective
This study aimed to investigate the changes and significance of circulating Helios-associated T cell subsets in patients with early-stage lung adenocarcinoma (LUAD).
Methods
Blood samples were collected from 35 healthy controls and 34 patients with early-stage LUAD. Flow cytometry was used to analyze various CD4+ T cell subsets, including regulatory T(Treg) cells, follicular regulatory T(Tfr) cells, follicular helper T (Tfh) cells, and conventional T (con-T) cells. Correlation analysis was conducted to investigate the association of Helios-related subsets with clinical indicators. The ROC curve was used to explore the potential clinical value of Helios+ T cell subsets in the screening of patients with early LUAD. Fifteen of these patients were tracked after lung cancer resection and changes in Helios+ T cell subsets before and after treatment were analyzed.
Results
The percentage and absolute number of Tregs were up-regulated in LUAD patients while Tfh and con-T cells expressing Helios were down-regulated. Absolute counts of Tfr and con-T cells and Helios expression in Tfr and Treg decreased significantly after resection. Helios+ Tfh and con-T were negatively correlated with certain tumor markers. Areas under the curve (AUCs) of percentages and absolute counts of Helios+ Tfh, Treg, Tfr and con-T cells to distinguish early LUAD from healthy individuals were 0.7277, 0.5697, 0.5718, 0.7210 (percentages), 0.7336, 0.7378, 0.5908 and 0.7445(absolute numbers), respectively.
Conclusion
Helios+ T cell subsets in peripheral blood of early-stage LUAD patients has changed significantly, which may be related to the pathogenesis of LUAD and could help for early diagnosis of LUAD.
{"title":"Alterations in Helios+ T cell subsets in peripheral blood of early-stage lung adenocarcinoma patients: Implications for early diagnosis","authors":"Yiming Zhao , Ming Zhao , Meng Li , Xiancan Ma , Mohan Zheng , Yuying Nie , Yaoyi Zhu , Jiaxin Ren , Ainizati Hasimu , Zihang Yuan , Qi Li , Ayibaota Bahabayi , Zhonghui Zhang , Xingyue Zeng , Chen Liu","doi":"10.1016/j.imbio.2023.152749","DOIUrl":"10.1016/j.imbio.2023.152749","url":null,"abstract":"<div><h3>Objective</h3><p><span>This study aimed to investigate the changes and significance of circulating Helios-associated T cell subsets </span>in patients<span> with early-stage lung adenocarcinoma (LUAD).</span></p></div><div><h3>Methods</h3><p>Blood samples were collected from 35 healthy controls and 34 patients with early-stage LUAD. Flow cytometry was used to analyze various CD4+ T cell subsets, including regulatory T(Treg) cells, follicular regulatory T(Tfr) cells, follicular helper T (Tfh) cells, and conventional T (con-T) cells. Correlation analysis was conducted to investigate the association of Helios-related subsets with clinical indicators. The ROC curve was used to explore the potential clinical value of Helios+ T cell subsets in the screening of patients with early LUAD. Fifteen of these patients were tracked after lung cancer resection and changes in Helios+ T cell subsets before and after treatment were analyzed.</p></div><div><h3>Results</h3><p>The percentage and absolute number of Tregs were up-regulated in LUAD patients while Tfh and con-T cells expressing Helios were down-regulated. Absolute counts of Tfr and con-T cells and Helios expression in Tfr and Treg decreased significantly after resection. Helios+ Tfh and con-T were negatively correlated with certain tumor markers. Areas under the curve (AUCs) of percentages and absolute counts of Helios+ Tfh, Treg, Tfr and con-T cells to distinguish early LUAD from healthy individuals were 0.7277, 0.5697, 0.5718, 0.7210 (percentages), 0.7336, 0.7378, 0.5908 and 0.7445(absolute numbers), respectively.</p></div><div><h3>Conclusion</h3><p>Helios+ T cell subsets in peripheral blood of early-stage LUAD patients has changed significantly, which may be related to the pathogenesis of LUAD and could help for early diagnosis of LUAD.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41102148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-19DOI: 10.1016/j.imbio.2023.152742
Tingting Zhou , Xinqi Wang , Jiangping Kong , Lingxiang Yu , Huimin Xie , Feier Wang , Shenqian Xu , Zongwen Shuai , Qiang Zhou , Faming Pan
Background
Ankylosing spondylitis (AS) is a common inflammatory arthritis without a reliable biomarker. The role of methylation and mRNA expression of PRICKLE1 promoter in the pathogenesis of ankylosing spondylitis remains unclear.
Methods
A two-stage case-control design was used to detect the characteristics of methyl group and transcriptome of PRICKLE1 gene in Ankylosing spondylitis. The methylation degree of PRICKLE1 gene promoter region was tested by phosphate-sequencing, and further analyzed whether there was significant difference in methylation level of PRICKLE1 gene. The expression levels of PRICKLE1 mRNA in 50 AS patients and 50 healthy controls were detected by real-time quantitative PCR (RT-qPCR).
Results
Compared with healthy control group, the intensity of methylation in 4 ponds of PRICKLE1 in patients with Ankylosing spondylitis was low, and the mRNA levels were overexpressed (P = 0.017). ROC results showed that the sensitivity of PRICKLE1 was 68.67% and specificity was 71.43%.
Conclusion
There is a significant change in the concentration of serum PRICKLE1 mRNAin patients with Ankylosing spondylitis, and the degree of gene methylation is significantly reduced, suggesting that PRICKLE1 gene maybe involved in the pathogenesis of Ankylosing spondylitis, which may be useful for predicting the occurrence of AS and finding new early screening indicators.
{"title":"PRICKLE1 gene methylation and abnormal transcription in Chinese patients with ankylosing spondylitis","authors":"Tingting Zhou , Xinqi Wang , Jiangping Kong , Lingxiang Yu , Huimin Xie , Feier Wang , Shenqian Xu , Zongwen Shuai , Qiang Zhou , Faming Pan","doi":"10.1016/j.imbio.2023.152742","DOIUrl":"10.1016/j.imbio.2023.152742","url":null,"abstract":"<div><h3>Background</h3><p>Ankylosing spondylitis (AS) is a common inflammatory arthritis without a reliable biomarker. The role of methylation and mRNA expression of PRICKLE1 promoter in the pathogenesis of ankylosing spondylitis remains unclear.</p></div><div><h3>Methods</h3><p>A two-stage case-control design was used to detect the characteristics of methyl group and transcriptome of PRICKLE1 gene in Ankylosing spondylitis. The methylation degree of PRICKLE1 gene promoter region was tested by phosphate-sequencing, and further analyzed whether there was significant difference in methylation level of PRICKLE1 gene. The expression levels of PRICKLE1 mRNA in 50 AS patients and 50 healthy controls were detected by real-time quantitative PCR (RT-qPCR).</p></div><div><h3>Results</h3><p>Compared with healthy control group, the intensity of methylation in 4 ponds of PRICKLE1 in patients with Ankylosing spondylitis was low, and the mRNA levels were overexpressed (<em>P</em> = 0.017). ROC results showed that the sensitivity of PRICKLE1 was 68.67% and specificity was 71.43%.</p></div><div><h3>Conclusion</h3><p>There is a significant change in the concentration of serum PRICKLE1 mRNAin patients with Ankylosing spondylitis, and the degree of gene methylation is significantly reduced, suggesting that PRICKLE1 gene maybe involved in the pathogenesis of Ankylosing spondylitis, which may be useful for predicting the occurrence of AS and finding new early screening indicators.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-15DOI: 10.1016/j.imbio.2023.152747
Amanda Goulart , Naira Ferreira Anchieta , Pedro Alexandre Sampaio , Vânia Brazão , Jefferson Luiz Da Silva , Gisele Bulhões Portapilla , Andressa Duarte , Daiane Yukie Tezuca , Maiara Voltarelli Providello , Angelita Maria Stabile , José Clóvis do Prado Júnior
Background
Obesity is a global problem associated with several conditions, including hypertension, diabetes, arthritis and cardiovascular diseases. With the increase in the prevalence of obesity in recent years, mostly in developing countries, it is important to study its impact on various diseases, including infectious illnesses, such as Chagas disease, caused by the protozoan Trypanosoma cruzi. Considering that a diet rich in salt, sugar, and fat is associated with obesity, this study aimed to evaluate the influence of cafeteria diet (CAF)-induced obesity on immune responses in T. cruzi-infected rats.
Methods
Male Wistar Hannover rats were provided with water and food ad libitum (chow group). The CAF-fed groups received a normal rodent diet or CAF. The animals were intraperitoneally infected with 105 trypomastigote forms of the Y strain of T. cruzi present in the whole blood from a previously infected mouse.
Results
CAF-fed rats showed a significant increase in visceral adipose tissue weight compared to chow-fed rats. A significant reduction in CD3+ CD4+ helper splenic T cells was observed in obese-infected rats compared to non-obese-infected rats, as well as CD11b and macrophages. In addition, macrophages from obese animals displayed reduced RT1b levels compared to those from control animals. Moreover, INF-γ, an important factor in macrophage activation, was reduced in obese-infected rats compared with their counterparts.
Conclusions
These results indicate that a CAF can impair the cell-mediated immune response against T. cruzi.
{"title":"Cafeteria diet-induced obesity remodels immune response in acute Trypanosoma cruzi infection","authors":"Amanda Goulart , Naira Ferreira Anchieta , Pedro Alexandre Sampaio , Vânia Brazão , Jefferson Luiz Da Silva , Gisele Bulhões Portapilla , Andressa Duarte , Daiane Yukie Tezuca , Maiara Voltarelli Providello , Angelita Maria Stabile , José Clóvis do Prado Júnior","doi":"10.1016/j.imbio.2023.152747","DOIUrl":"10.1016/j.imbio.2023.152747","url":null,"abstract":"<div><h3>Background</h3><p>Obesity is a global problem associated with several conditions, including hypertension, diabetes, arthritis and cardiovascular diseases. With the increase in the prevalence of obesity in recent years, mostly in developing countries, it is important to study its impact on various diseases, including infectious illnesses, such as Chagas disease, caused by the protozoan <em>Trypanosoma cruzi</em>. Considering that a diet rich in salt, sugar, and fat is associated with obesity, this study aimed to evaluate the influence of cafeteria diet (CAF)-induced obesity on immune responses in <em>T. cruzi</em>-infected rats.</p></div><div><h3>Methods</h3><p>Male <em>Wistar</em> Hannover rats were provided with water and food <em>ad libitum</em> (chow group). The CAF-fed groups received a normal rodent diet or CAF. The animals were intraperitoneally infected with 10<sup>5</sup> trypomastigote forms of the Y strain of <em>T. cruzi</em> present in the whole blood from a previously infected mouse.</p></div><div><h3>Results</h3><p>CAF-fed rats showed a significant increase in visceral adipose tissue weight compared to chow-fed rats. A significant reduction in CD3<sup>+</sup> CD4<sup>+</sup> helper splenic T cells was observed in obese-infected rats compared to non-obese-infected rats, as well as CD11b and macrophages. In addition, macrophages from obese animals displayed reduced RT1b levels compared to those from control animals. Moreover, INF-γ, an important factor in macrophage activation, was reduced in obese-infected rats compared with their counterparts.</p></div><div><h3>Conclusions</h3><p>These results indicate that a CAF can impair the cell-mediated immune response against <em>T. cruzi.</em></p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41126686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-15DOI: 10.1016/j.imbio.2023.152748
Melayne Rocha Aciole , Juliana Prado Gonçales , Patrícia Areias Feitosa Neves , Cynthia Regina Pedrosa Soares , Marta Iglis de Oliveira , Heloisa Ramos Lacerda de Melo , Reginaldo Gonçalves de Lima Neto , Líbia Cristina Rocha Vilela Moura , Paulo Sergio Ramos Araújo , Virginia Maria Barros de Lorena
The present study aimed to inspect the serum levels of the soluble receptors, sTNFR1 and sTNFR2, in patients with COVID-19. The large production of inflammatory cytokines is an essential process in the pathogenesis of COVID-19. TNF is a multifaceted proinflammatory cytokine which has soluble and membrane receptors. Thus, knowing the role of these receptors will help better understand this disease's immunopathogenesis. We included 131 patients confirmed for SARS-CoV-2, separated into three groups: ward patients without O2 support, group A (n = 14); ward patients with O2 support, group B (n = 85), and patients in an intensive care unit (ICU), group C (n = 32), making up the receptors dosed by flow cytometry. The results showed that sTNFR1 and sTNFR2 are associated with disease severity, being higher in group C when compared to group A. As for the levels of receptors and their relationship with the degree of lung involvement, we found higher values of sTNFR1 in patients in group 1 (pulmonary involvement < 25%), suggesting that inflammatory processes related to TNF are not necessarily associated with the primary site of infection. When we analysed the patients who passed away compared to those who recovered, both receptors significantly increased the mortality numbers. These findings suggest a relevant influence of soluble receptors in the inflammatory processes involved in the pathogenesis of COVID-19. Wherefore, we suggest using these receptors as biomarkers of severity and mortality of the disease.
{"title":"Levels of soluble TNF receptors (sTNFR1 and sTNFR2) increase with clinical worsening of patients and are related to COVID-19 mortality","authors":"Melayne Rocha Aciole , Juliana Prado Gonçales , Patrícia Areias Feitosa Neves , Cynthia Regina Pedrosa Soares , Marta Iglis de Oliveira , Heloisa Ramos Lacerda de Melo , Reginaldo Gonçalves de Lima Neto , Líbia Cristina Rocha Vilela Moura , Paulo Sergio Ramos Araújo , Virginia Maria Barros de Lorena","doi":"10.1016/j.imbio.2023.152748","DOIUrl":"10.1016/j.imbio.2023.152748","url":null,"abstract":"<div><p>The present study aimed to inspect the serum levels of the soluble receptors, sTNFR1 and sTNFR2, in patients with COVID-19. The large production of inflammatory cytokines is an essential process in the pathogenesis of COVID-19. TNF is a multifaceted proinflammatory cytokine which has soluble and membrane receptors. Thus, knowing the role of these receptors will help better understand this disease's immunopathogenesis. We included 131 patients confirmed for SARS-CoV-2, separated into three groups: ward patients without O2 support, group A (n = 14); ward patients with O2 support, group B (n = 85), and patients in an intensive care unit (ICU), group C (n = 32), making up the receptors dosed by flow cytometry. The results showed that sTNFR1 and sTNFR2 are associated with disease severity, being higher in group C when compared to group A. As for the levels of receptors and their relationship with the degree of lung involvement, we found higher values of sTNFR1 in patients in group 1 (pulmonary involvement < 25%), suggesting that inflammatory processes related to TNF are not necessarily associated with the primary site of infection. When we analysed the patients who passed away compared to those who recovered, both receptors significantly increased the mortality numbers. These findings suggest a relevant influence of soluble receptors in the inflammatory processes involved in the pathogenesis of COVID-19. Wherefore, we suggest using these receptors as biomarkers of severity and mortality of the disease.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045503/pdfft?md5=9cc98f1f35933cadcff9f9c456d6c2c0&pid=1-s2.0-S0171298523045503-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135346641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}