Pub Date : 2024-06-09DOI: 10.1016/j.imbio.2024.152824
Xueyan Jie, Dan Wang, Hongju Da, Hongxin Li, Hongyan Zhao, Jin He, Jianghao Liu, Yu Ma, Zhihui Qiang, Zhuoyang Li, Haicheng Zhong, Yun Liu
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.
最近的证据表明,T 细胞衰竭与过敏原特异性免疫疗法(AIT)有关。然而,T细胞衰竭在特异性免疫疗法中是如何发挥作用的还很不清楚。我们的研究旨在调查小鼠在过敏原特异性免疫治疗过程中与过敏原暴露相关的 T 细胞衰竭。我们构建了卵清蛋白(OVA)致敏的 C57BL/6J 哮喘小鼠和 AIT 小鼠模型。使用定量实时 PCR(qRTPCR)和流式细胞术监测 OVA 致敏小鼠局部和全身 CD4+ T 细胞以及 Th2+T 细胞衰竭的发生。与哮喘小鼠和对照组小鼠相比,AIT 小鼠 CD4+ T 细胞和 Th2+ T 细胞表面抑制性标记物程序性细胞死亡蛋白 1(PD-1)明显上调。哮喘小鼠 CD4+T 细胞表面的 PD-1 水平明显高于对照组小鼠。CD4+T细胞和Th2+T细胞表面的抑制性标志物细胞毒性T淋巴细胞相关蛋白4(CTLA-4)在AIT小鼠、哮喘小鼠和对照组小鼠之间无明显差异。总之,我们的研究表明,在 AIT 中,CD4+ T 细胞和 Th2+T 细胞上的 PD-1 表达增加。接触过敏原会促进 CD4+ T 细胞表面 PD-1 的表达。T 细胞衰竭在 AIT 中起着重要作用。
{"title":"Increased inhibitory surface marker PD-1 expression in CD4+T cells and Th2+T cells in allergen-specific immunotherapy","authors":"Xueyan Jie, Dan Wang, Hongju Da, Hongxin Li, Hongyan Zhao, Jin He, Jianghao Liu, Yu Ma, Zhihui Qiang, Zhuoyang Li, Haicheng Zhong, 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<sup>+</sup> T cells and Th2<sup>+</sup>T cells exhaustion in OVA-sensitized mice. The inhibitory surface marker programmed cell death protein 1 (PD-1) on CD4<sup>+</sup> T cells and Th2<sup>+</sup>T cells was significantly upregulated in AIT mice compared with asthmatic and control mice. The level of PD-1 on the surface of CD4<sup>+</sup>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<sup>+</sup> T cells and Th2<sup>+</sup>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<sup>+</sup> T cells and Th2<sup>+</sup>T cells was increased in AIT. Allergen exposure promotes the expression of PD-1 on the surface of CD4<sup>+</sup> T cells. T cell exhaustion plays an important role in AIT.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":null,"pages":null},"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}
Pub Date : 2024-06-09DOI: 10.1016/j.imbio.2024.152825
Background
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.
Methods
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 in vitro OA model, and the protein expression levels of OA biomarkers were detected by western blot.
Results
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. In vitro 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.
Conclusion
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.
背景骨关节炎(OA)是一种以软骨退化和关节炎症为特征的常见关节疾病。液-液相分离(LLPS)是一种参与细胞组织的生物物理过程,最近在 OA 研究中受到关注。我们分析了 GSE48556 数据集中的基因表达数据,以确定与 OA 相关的 LLPS 相关基因。我们利用差异表达分析、富集分析和机器学习算法探讨了 LLPS 相关基因在 OA 中的功能意义,并构建了 OA 诊断模型。此外,还以IL-1β为促炎因子建立了体外OA模型,并通过Western印迹检测了OA生物标志物的蛋白表达水平。富集分析表明,这些基因主要富集在 mRNA 代谢过程、细胞质颗粒和胰岛素抵抗中。利用机器学习算法筛选出了四个 OA 特征基因,包括 ADRB2、H3F3B、GNL3L 和 PELO。这些基因显示出令人满意的诊断价值。此外,这些生物标志物还与免疫细胞(包括 T 细胞 CD8 和单核细胞)有关。体外实验表明,IL-1β刺激会明显抑制软骨细胞的活力,并提高促炎因子的水平,从而模拟出OA的炎症状态。IL-1β组中GNL3L和H3F3B蛋白的表达水平明显低于对照组,而ADRB2和PELO的表达水平较高,这与生物信息学分析的结果一致。这些发现深入揭示了 OA 发病的分子机制,为开发新型治疗策略提供了机会。
{"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":null,"pages":null},"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}
Pub Date : 2024-06-06DOI: 10.1016/j.imbio.2024.152823
Martha Jackeline Pérez-Vega , Gerardo Manuel Corral-Ruiz , Adrian Galán-Salinas , Raúl Silva-García , Ismael Mancilla-Herrera , Jorge Barrios-Payán , Luis Fabila-Castillo , Rogelio Hernández-Pando , Luvia Enid Sánchez-Torres
Acute lung injury caused by severe malaria (SM) is triggered by a dysregulated immune response towards the infection with Plasmodium 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). P. berghei ANKA (PbA) 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 Entamoeba hystolitica. 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.
严重疟疾(SM)引起的急性肺损伤是由于对疟原虫感染的免疫反应失调所致。对人类肺部的尸检分析表明,肺泡弥漫性损伤(DAD)、CD8 淋巴细胞和中性粒细胞的存在以及细胞间粘附分子 1(ICAM-1)表达的增加。C57BL/6 小鼠感染 P. berghei ANKA(PbA)后再现了许多 SM 特征,包括以 DAD 为特征的急性肺损伤、肺实质中的 CD8+ T 淋巴细胞和中性粒细胞,以及促炎细胞因子和粘附分子(如 IFNγ、TNFα、ICAM 和 VCAM)的组织表达。由于这与免疫反应失调有关,因此建议使用免疫调节药物来减少 SM 的并发症。单核细胞运动抑制因子(MLIF)是一种免疫调节五肽,从子宫内膜实体虫的轴突培养物中分离出来。因此,我们评估了腹腔注射 MLIF 是否能预防 SM 诱导的急性肺损伤。该肽可预防SM,但无杀寄生虫作用,表明其保护作用与免疫反应的改变有关。此外,经感染处理的小鼠外周 CD8+ 白细胞和中性粒细胞比例较高。然而,治疗阻止了 DAD 和 CD8+ 细胞向肺组织的浸润,并下调了 IFNγ。此外,VCAM-1 的表达也有所减弱。这些结果表明,MLIF治疗可下调粘附分子的表达,阻碍细胞迁移和促炎细胞因子的产生,从而预防SM诱导的急性肺损伤。我们的研究结果代表了一种潜在的新策略,可在免疫反应失调引发肺损伤的各种情况下避免这种并发症。
{"title":"Acute lung injury is prevented by monocyte locomotion inhibitory factor in an experimental severe malaria mouse model","authors":"Martha Jackeline Pérez-Vega , Gerardo Manuel Corral-Ruiz , Adrian Galán-Salinas , Raúl Silva-García , Ismael Mancilla-Herrera , Jorge Barrios-Payán , Luis Fabila-Castillo , Rogelio Hernández-Pando , 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<sup>+</sup> 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<sup>+</sup> leukocytes and neutrophil proportions were higher in infected treated mice. However, the treatment prevented DAD, CD8<sup>+</sup> 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":null,"pages":null},"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}
Pub Date : 2024-06-06DOI: 10.1016/j.imbio.2024.152821
Ronghua Huo , Ruhua Zhao , Ziwen Li , Min Li , Yu Bin , Dongmei Wang , Gang Xue , Jingfang Wu , Xu Lin
Background
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.
Methods
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.
Results
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.
Conclusion
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.
{"title":"APOE expression in papillary thyroid carcinoma: Influencing tumor progression and macrophage polarization","authors":"Ronghua Huo , Ruhua Zhao , Ziwen Li , Min Li , Yu Bin , Dongmei Wang , Gang Xue , Jingfang Wu , 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":null,"pages":null},"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}
Pub Date : 2024-06-04DOI: 10.1016/j.imbio.2024.152822
Adib Miraki Feriz , Arezou Khosrojerdi , Nafiseh Erfanian , Setareh Azarkar , Seyed Mehdi Sajjadi , Mohammad Javad Shojaei , Mohammad Javad Vaferi , Hossein Safarpour , Vito Racanelli
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.
胰腺导管腺癌(PDAC)是一种致死率极高的恶性肿瘤,是癌症研究和临床治疗的重大挑战。在这项研究中,我们重新分析了已发表的来自PDAC和邻近组织的单细胞RNA测序(scRNA-seq)数据集,以研究肿瘤和正常组织的异质性,特别关注调节性T细胞(Tregs)及其与肿瘤微环境(TME)中其他细胞的相互作用。根据特定基因的表达,Treg细胞被鉴定并分为天然Treg(nTreg)和诱导Treg(iTreg)。研究发现,肿瘤中 iTregs 的数量高于健康组织,而健康组织中 n Tregs 的数量更高。研究还进行了差异基因表达分析和生物过程分析,发现PDAC中的Tregs主要参与蛋白靶向和翻译通路。此外,还发现了Tregs与其他细胞类型之间的配体-受体对,并揭示了Tregs与内皮细胞和导管细胞之间的关键通讯通路,这可能是PDAC免疫抑制TME的潜在原因。这些发现深入揭示了Tregs在PDAC中的作用及其与TME中其他类型细胞的相互作用,突出了免疫疗法的潜在靶点,如已知在Tregs上表达的抑制性免疫检查点受体CTLA4和TIGIT,它们已被证明在抑制抗肿瘤免疫反应中发挥作用。
{"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 , Arezou Khosrojerdi , Nafiseh Erfanian , Setareh Azarkar , Seyed Mehdi Sajjadi , Mohammad Javad Shojaei , Mohammad Javad Vaferi , Hossein Safarpour , 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":null,"pages":null},"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}
Pub Date : 2024-05-31DOI: 10.1016/j.imbio.2024.152807
E. Modzelewska , A. Wajda , A. Lutkowska , A. Felis-Giemza , B. Stypińska , A. Matusiewicz , M. Puszczewicz , D. Majewski , P.P. Jagodziński , E. Haładyj , A. Paradowska-Gorycka
The study aimed to explore the pontential impact of 10 polymorphisms within IFN-α, IFN-β1, IFN-γ and TLR3 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 IFN-γ rs2069705, IFN-γ rs2069718 and IFN-α rs3758236 polymorphisms have a protective role in SLE. We observed relations between TLR3 rs3775292, IFN-β1 rs7873167, IFN-γ rs2069705, TLR3 rs3775291 and TLR3 rs5743305 polymorphisms and clinical picture of SLE patients. We found associations between the IFN-α rs3758236, IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493 and IFN-β1 rs10964831 polymorphisms and the clinical manifestation of the SLE and/or its comorbidities. We perceived links between IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493, TLR3 rs3775291, TLR3 rs3775292 and TLR3 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.
{"title":"Variations in the interferon and TLR3 genes may be associated with susceptibility to systemic lupus erythematosus and its clinical presentation","authors":"E. Modzelewska , A. Wajda , A. Lutkowska , A. Felis-Giemza , B. Stypińska , A. Matusiewicz , M. Puszczewicz , D. Majewski , P.P. Jagodziński , E. Haładyj , 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":null,"pages":null},"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}
Pub Date : 2024-05-24DOI: 10.1016/j.imbio.2024.152813
Laura Bergantini, Sara Gangi, Miriana d’Alessandro, Paolo Cameli, Beatrice Perea, Martina Meocci, Gaia Fabbri, Francesco Bianchi, Elena Bargagli
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.
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.
{"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, Sara Gangi, Miriana d’Alessandro, Paolo Cameli, Beatrice Perea, Martina Meocci, Gaia Fabbri, Francesco Bianchi, 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":null,"pages":null},"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}
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.
Method
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.
Result
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.
Conclusion
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.
{"title":"Single-cell transcriptome analysis of macrophage subpopulations contributing to chemotherapy resistance in ovarian cancer","authors":"Xiaolin Zhong , Fei Zhang , Hongyang Xiao , 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<sup>+</sup> macrophages, THBS1<sup>+</sup> macrophages, and MMP9<sup>+</sup> 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<sup>+</sup>, THBS1<sup>+</sup>, and MMP9<sup>+</sup> 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":null,"pages":null},"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}
Pub Date : 2024-05-01DOI: 10.1016/j.imbio.2024.152810
Qiyin Zong , Hao Zhang , Futing Liu , Jianfei Li , Qian Liu , Zhi Duan , Wanlu Duan , Mengqi Ruan , Jingjing Zhang , Yan Liu , Qiang Zhou , Qin Wang
Background and aims
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.
Methods
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.
Results
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.
Conclusion
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.
{"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 , Hao Zhang , Futing Liu , Jianfei Li , Qian Liu , Zhi Duan , Wanlu Duan , Mengqi Ruan , Jingjing Zhang , Yan Liu , Qiang Zhou , 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":null,"pages":null},"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}
Pub Date : 2024-05-01DOI: 10.1016/j.imbio.2024.152812
Yue Zhang , Daqi Jia , Yipeng Wu , Yongqing Xu
Kangfuxin has been widely recognized for its use in treating ulcerative conditions and mucositis, primarily due to its anti-inflammatory properties, which promote cell proliferation, granulation tissue growth, and angiogenesis. However, the exact mechanisms underlying these effects remain poorly understood. In this study, we employed high-throughput mass spectrometry to identify 11 compounds in Kangfuxin, including uracil, hypoxanthine, xanthine, inosine, glutamic acid, glycine, alanine, valine, isoleucine, leucine, and lysine. Notably, the antipyretic and anti-inflammatory properties of inosine, one of these compounds, have not been well characterized. To address this gap, we induced fever in vivo using lipopolysaccharide (LPS) and conducted various experiments, including the analysis of endogenous mediators, inflammatory factors, quantitative polymerase chain reaction (QPCR), Western blotting, and hematoxylin and eosin (HE) staining. Our findings indicate that inosine significantly reduces LPS-induced fever, inhibits the expression of inflammatory factors, and alleviates the inflammatory response. These results suggest that inosine may serve as a potential therapeutic target for inflammatory diseases.
{"title":"Antipyretic and anti-inflammatory effects of inosine, an active component of Kangfuxin","authors":"Yue Zhang , Daqi Jia , Yipeng Wu , Yongqing Xu","doi":"10.1016/j.imbio.2024.152812","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152812","url":null,"abstract":"<div><p>Kangfuxin has been widely recognized for its use in treating ulcerative conditions and mucositis, primarily due to its anti-inflammatory properties, which promote cell proliferation, granulation tissue growth, and angiogenesis. However, the exact mechanisms underlying these effects remain poorly understood. In this study, we employed high-throughput mass spectrometry to identify 11 compounds in Kangfuxin, including uracil, hypoxanthine, xanthine, inosine, glutamic acid, glycine, alanine, valine, isoleucine, leucine, and lysine. Notably, the antipyretic and anti-inflammatory properties of inosine, one of these compounds, have not been well characterized. To address this gap, we induced fever in vivo using lipopolysaccharide (LPS) and conducted various experiments, including the analysis of endogenous mediators, inflammatory factors, quantitative polymerase chain reaction (QPCR), Western blotting, and hematoxylin and eosin (HE) staining. Our findings indicate that inosine significantly reduces LPS-induced fever, inhibits the expression of inflammatory factors, and alleviates the inflammatory response. These results suggest that inosine may serve as a potential therapeutic target for inflammatory diseases.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000305/pdfft?md5=a0a9daf915cdcdab7fe546ec0fd73801&pid=1-s2.0-S0171298524000305-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141083215","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}