Immunobiology最新文献

{"title":"Exploring the role of pyroptosis and immune infiltration in sepsis based on bioinformatic analysis","authors":"Zhi-hua Li,&nbsp;Yi Wang,&nbsp;Xiang-you Yu","doi":"10.1016/j.imbio.2024.152826","DOIUrl":"10.1016/j.imbio.2024.152826","url":null,"abstract":"<div><h3>Purpose</h3><p>Sepsis is a disease that is typically treated in intensive care units with high mortality and morbidity. Pyroptosis is a newly identified type of programmed cell death and is characterized by inflammatory cytokine secretion. However, the role of pyroptosis in sepsis remains unclear.</p></div><div><h3>Methods</h3><p>GSE28750 and GSE134347 datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed pyroptosis genes (DEPGs) were identified between sepsis and healthy controls. Machine learning was used to further narrow the gene range. Receiver operating curves (ROC) were generated to estimate the diagnostic efficacy. Immune infiltration levels were estimated via single-sample gene set enrichment analysis (ssGSEA). A network database was used to predict the upstream transcription factors and miRNAs of DEPGs. Finally, the expression of the genes was validated by qRT-PCR between sepsis patients and healthy controls.</p></div><div><h3>Results</h3><p>We found that the pyroptosis pathway was enriched and activated in sepsis. 8 DEPGs were identified. A heatmap showed that the genes, NLRC4, NAIP, IL-18, AIM2 and ELANE, were abundant in the sepsis samples, and the genes, NLRP1, CHMP7 and TP53, were abundant in the healthy control samples. The ssGSEA results showed that the abundances of activated dendritic cells, MDSC, macrophage, plasmacytoid dendritic cells, regulatory T-cells, and Th17-cells were significantly higher, while the activated B-cell, activated CD8 T-cell, CD56 dim tural killer cell, immature B-cell, monocyte, and T follicular helper cell abundances were lower in sepsis samples compared to healthy controls. The qRT-PCR results showed that the expression levels of NAIP, IL-18, TP53, CHMP7, NLRC4, ELANE and NLRP1 were consistant with the bioinformatic analyses, while the expression level of AIM2 has no significant difference.</p></div><div><h3>Conclusion</h3><p>Our study identified seven potential pyroptosis-related genes, NAIP, IL-18, TP53, CHMP7, NLRC4, ELANE and NLRP1. This study revealed that pyroptosis may promote sepsis development by activating the immune response.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152826"},"PeriodicalIF":2.5,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000445/pdfft?md5=6e8101f3053c6d00afaa0af283ad3480&pid=1-s2.0-S0171298524000445-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141405282","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}

{"title":"Increased inhibitory surface marker PD-1 expression in CD4+T cells and Th2+T cells in allergen-specific immunotherapy","authors":"Xueyan Jie,&nbsp;Dan Wang,&nbsp;Hongju Da,&nbsp;Hongxin Li,&nbsp;Hongyan Zhao,&nbsp;Jin He,&nbsp;Jianghao Liu,&nbsp;Yu Ma,&nbsp;Zhihui Qiang,&nbsp;Zhuoyang Li,&nbsp;Haicheng Zhong,&nbsp;Yun Liu","doi":"10.1016/j.imbio.2024.152824","DOIUrl":"10.1016/j.imbio.2024.152824","url":null,"abstract":"<div><p>Recent evidence has shown that T cell exhaustion is implicated in Allergen-specific Immunotherapy (AIT). However, how T cell exhaustion plays a role in AIT is far from clear. Our study aimed to investigate T cell exhaustion associated with allergen exposure during AIT in mice. Ovalbumin (OVA) − sensitized C57BL/6J asthma mouse and AIT mouse models were constructed. Quantitative real-time PCR (qRTPCR) and flow cytometry were used to monitor the occurrence of local and systemic CD4⁺ T cells and Th2⁺T cells exhaustion in OVA-sensitized mice. The inhibitory surface marker programmed cell death protein 1 (PD-1) on CD4⁺ T cells and Th2⁺T cells was significantly upregulated in AIT mice compared with asthmatic and control mice. The level of PD-1 on the surface of CD4⁺T cells of asthma mice was significantly higher than that of control mice. The inhibitory surface marker cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on CD4⁺ T cells and Th2⁺T cells showed no significant difference between the AIT, asthma and control mice. Collectively, our study indicated that the expression of PD-1 on CD4⁺ T cells and Th2⁺T cells was increased in AIT. Allergen exposure promotes the expression of PD-1 on the surface of CD4⁺ T cells. T cell exhaustion plays an important role in AIT.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 4","pages":"Article 152824"},"PeriodicalIF":2.8,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000421/pdfft?md5=f8679ed2bde9c5795007f010aaed4c13&pid=1-s2.0-S0171298524000421-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320762","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}

{"title":"Exploring liquid-liquid phase separation-related diagnostic biomarkers in osteoarthritis based on machine learning algorithms and experiment","authors":"","doi":"10.1016/j.imbio.2024.152825","DOIUrl":"10.1016/j.imbio.2024.152825","url":null,"abstract":"<div><h3>Background</h3><p>Osteoarthritis (OA) is a prevalent joint disorder characterized by cartilage degeneration and joint inflammation. Liquid-liquid phase separation (LLPS), a biophysical process involved in cellular organization, has recently gained attention in OA research. However, the relationship between LLPS and OA remains poorly understood.</p></div><div><h3>Methods</h3><p>We analyzed gene expression data from the GSE48556 dataset to identify LLPS-related genes associated with OA. Differential expression analysis, enrichment analyses, and machine learning algorithms were employed to explore the functional significance of LLPS-related genes in OA and then construct a diagnostic model for OA. In addition, IL-1β as a pro-inflammatory factor to establish an <em>in vitro</em> OA model, and the protein expression levels of OA biomarkers were detected by western blot.</p></div><div><h3>Results</h3><p>A total of 145 LLPS-related genes were screened in OA samples. Enrichment analyses revealed these genes were mainly enriched in mRNA metabolic processes, cytoplasmic granules, and insulin resistance. Four characteristic genes for OA were selected by using machine learning algorithms, including ADRB2, H3F3B, GNL3L, and PELO. These genes showed satisfactory diagnostic values. Furthermore, there were association between these biomarkers and immune cells, including T cells CD8 and monocytes. <em>In vitro</em> experiments showed that IL-1β stimulation significantly inhibited the cell viability of chondrocytes and enhanced the levels of pro-inflammatory factors, that could mimic the inflammatory state of OA. The expression levels of GNL3L and H3F3B proteins in IL-1β group were obviously lower than those in control group, while levels of ADRB2 and PELO were higher, which was consistent with the results of bioinformatics analysis.</p></div><div><h3>Conclusion</h3><p>Our study identifies LLPS-related genes as potential diagnostic biomarkers for OA. These findings provide insights into the molecular mechanisms underlying OA pathogenesis and offer opportunities for the development of novel therapeutic strategies.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152825"},"PeriodicalIF":2.5,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000433/pdfft?md5=eb2e72ca2e466c1becb11114915ca223&pid=1-s2.0-S0171298524000433-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141413943","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}

{"title":"Acute lung injury is prevented by monocyte locomotion inhibitory factor in an experimental severe malaria mouse model","authors":"Martha Jackeline Pérez-Vega ,&nbsp;Gerardo Manuel Corral-Ruiz ,&nbsp;Adrian Galán-Salinas ,&nbsp;Raúl Silva-García ,&nbsp;Ismael Mancilla-Herrera ,&nbsp;Jorge Barrios-Payán ,&nbsp;Luis Fabila-Castillo ,&nbsp;Rogelio Hernández-Pando ,&nbsp;Luvia Enid Sánchez-Torres","doi":"10.1016/j.imbio.2024.152823","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152823","url":null,"abstract":"<div><p>Acute lung injury caused by severe malaria (SM) is triggered by a dysregulated immune response towards the infection with <em>Plasmodium</em> parasites. Postmortem analysis of human lungs shows diffuse alveolar damage (DAD), the presence of CD8 lymphocytes, neutrophils, and increased expression of Intercellular Adhesion Molecule 1 (ICAM-1). <em>P. berghei</em> ANKA (<em>Pb</em>A) infection in C57BL/6 mice reproduces many SM features, including acute lung injury characterized by DAD, CD8⁺ T lymphocytes and neutrophils in the lung parenchyma, and tissular expression of proinflammatory cytokines and adhesion molecules, such as IFNγ, TNFα, ICAM, and VCAM. Since this is related to a dysregulated immune response, immunomodulatory agents are proposed to reduce the complications of SM. The monocyte locomotion inhibitory factor (MLIF) is an immunomodulatory pentapeptide isolated from axenic cultures of <em>Entamoeba hystolitica.</em> Thus, we evaluated if the MLIF intraperitoneal (i.p.) treatment prevented SM-induced acute lung injury. The peptide prevented SM without a parasiticidal effect, indicating that its protective effect was related to modifications in the immune response. Furthermore, peripheral CD8⁺ leukocytes and neutrophil proportions were higher in infected treated mice. However, the treatment prevented DAD, CD8⁺ cell infiltration into the pulmonary tissue and downregulated IFNγ. Moreover, VCAM-1 expression was abrogated. These results indicate that the MLIF treatment downregulated adhesion molecule expression, impeding cell migration and proinflammatory cytokine tissular production, preventing acute lung injury induced by SM. Our findings represent a potential novel strategy to avoid this complication in various events where a dysregulated immune response triggers lung injury.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 4","pages":"Article 152823"},"PeriodicalIF":2.8,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S017129852400041X/pdfft?md5=26319187ec811414fa1737f8bf61030f&pid=1-s2.0-S017129852400041X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297943","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}

{"title":"APOE expression in papillary thyroid carcinoma: Influencing tumor progression and macrophage polarization","authors":"Ronghua Huo ,&nbsp;Ruhua Zhao ,&nbsp;Ziwen Li ,&nbsp;Min Li ,&nbsp;Yu Bin ,&nbsp;Dongmei Wang ,&nbsp;Gang Xue ,&nbsp;Jingfang Wu ,&nbsp;Xu Lin","doi":"10.1016/j.imbio.2024.152821","DOIUrl":"10.1016/j.imbio.2024.152821","url":null,"abstract":"<div><h3>Background</h3><p>As metastatic papillary thyroid carcinoma becomes increasingly challenging to treat, immunotherapy has emerged as a new research direction. Tumor-associated macrophages (TAMs) influence the occurrence, invasion, and metastasis of tumors. Apolipoprotein E (APOE) can regulate the polarization changes of macrophages and participate in the remodeling of the tumor microenvironment. However, the role of APOE in regulating the polarization and biological functions of TAMs in papillary thyroid carcinoma (PTC) remains unclear, as it acts as a dual biomarker.</p></div><div><h3>Methods</h3><p>We probed APOE expression in PTC tissues using immunohistochemical staining. A cell co-culture model was established where different APOE-expressing K1 cells were co-cultured with THP-1-derived M0 macrophages. An in-depth analysis of macrophage polarization behavior was performed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. Subsequently, the impact of APOE-regulated macrophages on tumor cell behavior, especially proliferation, migration, and invasion, was evaluated utilizing IncuCyte ZOOM system, flow cytometry, colony formation, and scratch experiments. Finally, we used a xenograft model to confirm the effects of APOE on PTC tumorigenesis.</p></div><div><h3>Results</h3><p>Tumor dimensions, stage, and lymphatic metastases were significantly associated with increased APOE expression in PTC tissues. K1 cells were markedly limited in their proliferation, migration, and invasion abilities when APOE expression was silenced, a process mediated by the PI3K/Akt/NF-κB signaling axis. Moreover, APOE is a key facilitator of the enhancement of the anti-inflammatory cytokines IL-10 and TGF-β1. In PTC cellular models, APOE contributed to the phenotypic shift of THP-1 derived macrophages towards an M2 phenotypic polarization, predominantly through the modulation of IL-10. Furthermore, in vivo studies involving athymic nude mice have demonstrated pivotal role of APOE in tumor progression and the induction of M2-like TAM polarization.</p></div><div><h3>Conclusion</h3><p>Our results elucidated that APOE could promote the shift of TAMs from M0-type to M2-type polarization by regulating inflammatory factors expressions in K1 cell through the PI3K/Akt/NF-κB pathway. These findings are crucial for understanding the molecular mechanisms underlying PTC pathogenesis and for developing immunological drugs to treat this disease.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152821"},"PeriodicalIF":2.5,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000391/pdfft?md5=8a66ffb600ffb24e81930d94c9b0f7e5&pid=1-s2.0-S0171298524000391-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141407760","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}

{"title":"Targeting the dynamic transcriptional landscape of Treg subpopulations in pancreatic ductal adenocarcinoma: Insights from single-cell RNA sequencing analysis with a focus on CTLA4 and TIGIT","authors":"Adib Miraki Feriz ,&nbsp;Arezou Khosrojerdi ,&nbsp;Nafiseh Erfanian ,&nbsp;Setareh Azarkar ,&nbsp;Seyed Mehdi Sajjadi ,&nbsp;Mohammad Javad Shojaei ,&nbsp;Mohammad Javad Vaferi ,&nbsp;Hossein Safarpour ,&nbsp;Vito Racanelli","doi":"10.1016/j.imbio.2024.152822","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152822","url":null,"abstract":"<div><p>Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy that represents a significant challenge in cancer research and clinical management. In this study, we reanalyzed a published single-cell RNA sequencing (scRNA-seq) dataset from PDAC and adjacent tissues to investigate the heterogeneity of tumor and normal tissue, specifically focusing on the regulatory T cells (Tregs) and their interactions with other cells in the tumor microenvironment (TME). Treg cells were identified and clustered into natural Tregs (nTreg) and induced Tregs (iTreg) based on the expression of specific genes. It was found that the number of iTregs was higher in the tumor than in healthy tissues, while the number of n Tregs was higher in healthy tissues. Differential gene expression analysis was performed, and biological process analysis revealed that the Tregs in PDAC were mostly involved in protein targeting and translation pathways. In addition, ligand-receptor pairs between Tregs and other cell types were identified, and the critical communication pathways between Tregs and endothelial and ductal cells were revealed, which could potentially contribute to the immunosuppressive TME of PDAC. These findings provide insights into the role of Tregs in PDAC and their interactions with other cell types in the TME, highlighting potential targets for immunotherapy, such as the inhibitory immune checkpoint receptors CTLA4 and TIGIT, which are known to be expressed on Tregs and have been shown to play a role in suppressing anti-tumor immune responses.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 4","pages":"Article 152822"},"PeriodicalIF":2.8,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000408/pdfft?md5=7ab292ccc8ea385fe038100ea6310ef4&pid=1-s2.0-S0171298524000408-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141291975","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}

{"title":"Variations in the interferon and TLR3 genes may be associated with susceptibility to systemic lupus erythematosus and its clinical presentation","authors":"E. Modzelewska ,&nbsp;A. Wajda ,&nbsp;A. Lutkowska ,&nbsp;A. Felis-Giemza ,&nbsp;B. Stypińska ,&nbsp;A. Matusiewicz ,&nbsp;M. Puszczewicz ,&nbsp;D. Majewski ,&nbsp;P.P. Jagodziński ,&nbsp;E. Haładyj ,&nbsp;A. Paradowska-Gorycka","doi":"10.1016/j.imbio.2024.152807","DOIUrl":"10.1016/j.imbio.2024.152807","url":null,"abstract":"<div><p>The study aimed to explore the pontential impact of 10 polymorphisms within <em>IFN-α</em>, <em>IFN-β1</em>, <em>IFN-γ</em> and <em>TLR3</em> genes on SLE phenotype and susceptibility and to study the relationship between specific genotypes and clinics. Whole blood samples from SLE patients and healthy controls was obtained. DNA was extracted from the peripheral blood by the QIAamp DNA Blood Mini Kit (Qiagen). The quality and quantity of isolated DNA was estimated by the Quawell Q5000 spectrophotometer. We genotyped SLE patients and healthy subjects using real-time PCR (QuantStudio 5 thermocycler). The study suggests that <em>IFN-γ</em> rs2069705, <em>IFN-γ</em> rs2069718 and <em>IFN-α</em> rs3758236 polymorphisms have a protective role in SLE. We observed relations between <em>TLR3</em> rs3775292, <em>IFN-β1</em> rs7873167, <em>IFN-γ</em> rs2069705, <em>TLR3</em> rs3775291 and <em>TLR3</em> rs5743305 polymorphisms and clinical picture of SLE patients. We found associations between the <em>IFN-α</em> rs3758236, <em>IFN-γ</em> rs2069705, <em>IFN-γ</em> rs2069718, <em>IFN-γ</em> rs1861493 and <em>IFN-β1</em> rs10964831 polymorphisms and the clinical manifestation of the SLE and/or its comorbidities. We perceived links between <em>IFN-γ</em> rs2069705, <em>IFN-γ</em> rs2069718, <em>IFN-γ</em> rs1861493, <em>TLR3</em> rs3775291, <em>TLR3</em> rs3775292 and <em>TLR3</em> rs5743305 polymorphisms and the occurrence of autoantibodies. Our study presented the relationship between IFN and TLR gene polymorphisms with SLE susceptibility, phenotype and autoantibodies profile. This study propose that polymorphisms within interferons and TLR3 genes can be engaged in the SLE pathogenesis and course.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 4","pages":"Article 152807"},"PeriodicalIF":2.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000251/pdfft?md5=c319ca0f2f1222e8633292a0bb1a8ecf&pid=1-s2.0-S0171298524000251-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183668","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}

{"title":"Altered serum concentrations of IL-8, IL-32 and IL-10 in patients with lung impairment 6 months after COVID-19","authors":"Laura Bergantini,&nbsp;Sara Gangi,&nbsp;Miriana d’Alessandro,&nbsp;Paolo Cameli,&nbsp;Beatrice Perea,&nbsp;Martina Meocci,&nbsp;Gaia Fabbri,&nbsp;Francesco Bianchi,&nbsp;Elena Bargagli","doi":"10.1016/j.imbio.2024.152813","DOIUrl":"10.1016/j.imbio.2024.152813","url":null,"abstract":"<div><p>Post-COVID symptoms are reported in 10–35 % of patients not requiring hospitalization, and in up to 80 % of hospitalized patients and patients with severe disease. The pathogenesis of post-COVID syndrome remains largely unknown. Some evidence suggests that prolonged inflammation has a key role in the pathogenesis of most post-COVID manifestations. We evaluated a panel of inflammatory and immune-mediated cytokines in individuals with altered HRCT features and in patients without any long-term COVID symptoms. Blood samples of 89 adult patients previously hospitalized with COVID-19 were collected and stratified as patients with and without HRCT evidence of fibrotic lung alterations. Serum analyte concentrations of IL-4, IL-2, CXCL10 (IP-10), IL-1β, TNF-α, CCL2 (MCP-1), IL-17A, IL-6, IL-10, IFN-γ, IL-12p70 and TGF-β1 (free active form) were quantified by bead-based multiplex assay. Clinical and functional data were recorded in a database.</p><p>With the use of machine learning approach, IL-32, IL-8, and IL-10 proved to be associated with the development of HRCT evidence of lung sequelae at follow-up. Direct comparison of cytokine levels in the two groups showed increased levels of IL-32 and decreased levels of IL-8 in patients with lung impairment. After further stratification of patients by severity (severe versus mild/moderate) during hospitalization, IL-10 emerged as the only cytokine showing decreased levels in severe patients. These findings contribute to a better understanding of the immune response and potential prognostic markers in patients with lung sequelae after COVID-19.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 4","pages":"Article 152813"},"PeriodicalIF":2.8,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000317/pdfft?md5=ef9af97e3922b78587ba4d6233126d7b&pid=1-s2.0-S0171298524000317-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141145153","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}

{"title":"Single-cell transcriptome analysis of macrophage subpopulations contributing to chemotherapy resistance in ovarian cancer","authors":"Xiaolin Zhong ,&nbsp;Fei Zhang ,&nbsp;Hongyang Xiao ,&nbsp;Ruiqing Tu","doi":"10.1016/j.imbio.2024.152811","DOIUrl":"10.1016/j.imbio.2024.152811","url":null,"abstract":"<div><h3>Background</h3><p>Ovarian cancer, a fatal gynecological malignancy, is primarily managed through surgery and chemotherapy. However, a significant challenge arises as patients frequently experience relapse due to chemotherapy resistance. This study delves into the complex functions and underlying mechanisms of macrophages in chemotherapy resistance in ovarian cancer.</p></div><div><h3>Method</h3><p>The single-cell transcriptome sequencing data of ovarian cancer with or without chemotherapy were analyzed. Then, corresponding cell types were identified, and macrophages were extracted from all cells. Following the standardized single-cell analysis using the Seurat package, 15 distinct macrophage clusters were found and differentially expressed genes among them were analyzed. Moreover, their association with chemotherapy resistance was explored through cell proportions and gene expression.</p></div><div><h3>Result</h3><p>In the single-cell transcriptomic analysis of ovarian cancer tissues before and after chemotherapy, the cellular proportion of CXCL5⁺ macrophages, THBS1⁺ macrophages, and MMP9⁺ macrophages were significantly increased following chemotherapy. Further investigation revealed that these macrophage subpopulations upregulated the expression of multiple pro-tumorigenic angiogenic or invasive factors, in addition to CXCL5, THBS1, and MMP9, including CTSL, CXCL1, and CCL18. Finally, pathway enrichment analysis revealed the significant activation of signaling pathways, such as NOD-like receptor, MAPK, and TNF in these macrophage subpopulations, which provides direction for studying the mechanism of these subpopulations.</p></div><div><h3>Conclusion</h3><p>CXCL5⁺, THBS1⁺, and MMP9⁺ macrophage subpopulations exhibit an increased cellular prevalence post-chemotherapy and pro-tumorigenic molecular expression profiles, suggesting a close association with chemoresistance in ovarian cancer. These findings contribute to our understanding of the roles and mechanisms of macrophages in ovarian cancer chemoresistance, providing a theoretical basis and direction for the development of therapies targeting macrophages in overcoming ovarian cancer chemoresistance.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152811"},"PeriodicalIF":2.5,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000299/pdfft?md5=16a380283ad6102df75ef62fc7b99dbe&pid=1-s2.0-S0171298524000299-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141133235","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}

{"title":"Activation of the cGAS-STING pathway by viral dsDNA leading to M1 polarization of macrophages mediates antiviral activity against hepatitis B virus","authors":"Qiyin Zong ,&nbsp;Hao Zhang ,&nbsp;Futing Liu ,&nbsp;Jianfei Li ,&nbsp;Qian Liu ,&nbsp;Zhi Duan ,&nbsp;Wanlu Duan ,&nbsp;Mengqi Ruan ,&nbsp;Jingjing Zhang ,&nbsp;Yan Liu ,&nbsp;Qiang Zhou ,&nbsp;Qin Wang","doi":"10.1016/j.imbio.2024.152810","DOIUrl":"10.1016/j.imbio.2024.152810","url":null,"abstract":"<div><h3>Background and aims</h3><p>Activation of the cGAS-STING pathway induces the production of type I interferons, initiating the antiviral immune response, which contributes to the clearance of pathogens. Previous studies have shown that STING agonists promote hepatitis B virus (HBV) clearance; however, few studies have investigated the effect of activating the cGAS-STING pathway in macrophages on HBV.</p></div><div><h3>Methods</h3><p>The polarization status of HBV particle-stimulated RAW264.7 macrophages was analyzed. After stimulation with HBV particles, the analysis focused on determining whether the DNA sensors in RAW264.7 macrophages recognized the viral double-stranded DNA (dsDNA) and evaluating the activation of the cGAS-STING pathway. Coculture of mouse macrophages and hepatocytes harboring HBV was used to study the antiviral activity of HBV-stimulated RAW264.7 macrophages.</p></div><div><h3>Results</h3><p>After stimulation with HBV particles, HBV relaxed circular DNA (rcDNA) was detected in RAW264.7 macrophages, and the protein expression of phospho-STING, phospho-TBK1, and phospho-IRF3 in the STING pathway was increased, as shown by Western blot analysis, which revealed that M1 polarization of macrophages was caused by increased expression of CD86. RT–PCR analyses revealed elevated expression of M1 macrophage polarization-associated cytokines such as TNFα, IL-1β, iNOS, and IFNα/β. In the coculture experiment, both HBsAg and HBeAg expression levels were significantly decreased in AML12-HBV1.3 cells cocultured with the supernatants of HBV-stimulated RAW264.7 macrophages.</p></div><div><h3>Conclusion</h3><p>The results suggest that macrophages can endocytose HBV particles. Additionally, viral dsDNA can be recognized by DNA pattern recognition receptors, which in turn activate the cGAS-STING pathway, promoting the M1 polarization of macrophages, while no significant M2 polarization is observed. Macrophages stimulated with HBV particles exhibit enhanced antiviral activity against HBV.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152810"},"PeriodicalIF":2.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000287/pdfft?md5=3e9abaec68e88266eb8af05ce306528c&pid=1-s2.0-S0171298524000287-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141023275","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}