Dendritic cells (DCs) are specialized antigen-presenting cells that are crucial for maintaining self-tolerance, initiating immune responses against pathogens, and patrolling body compartments. Despite promising aspects, DC-based immunotherapy faces challenges that include limited availability, immune escape in tumors, immunosuppression in the tumor microenvironment, and the need for effective combination therapies. A further limitation in DC-based immunotherapy is the low population of migratory DC (around 5%–10%) that migrate to lymph nodes (LNs) through afferent lymphatics depending on the LN draining site. By increasing the population of migratory DCs, DC-based immunotherapy could enhance immunotherapeutic effects on target diseases. This paper reviews the importance of DC migration and current research progress in the context of DC-based immunotherapy.
树突状细胞（DC）是一种特化的抗原递呈细胞，对于维持自身耐受性、启动针对病原体的免疫反应以及在体内各区巡视至关重要。尽管DC免疫疗法前景广阔，但也面临着一些挑战，包括可用性有限、肿瘤中的免疫逃逸、肿瘤微环境中的免疫抑制，以及需要有效的联合疗法。基于 DC 的免疫疗法的另一个限制因素是可迁移 DC 的数量较少（约 5%-10%），这些 DC 会根据淋巴结引流部位通过传入淋巴管迁移到淋巴结。通过增加迁移性 DC 的数量，以 DC 为基础的免疫疗法可提高对目标疾病的免疫治疗效果。本文回顾了直流电迁移的重要性以及目前在基于直流电的免疫疗法方面的研究进展。
{"title":"Dendritic Cell-Based Immunotherapy: The Importance of Dendritic Cell Migration","authors":"Min-Seon Song, Ji-Hee Nam, Kyung-Eun Noh, Dae-Seog Lim","doi":"10.1155/2024/7827246","DOIUrl":"https://doi.org/10.1155/2024/7827246","url":null,"abstract":"Dendritic cells (DCs) are specialized antigen-presenting cells that are crucial for maintaining self-tolerance, initiating immune responses against pathogens, and patrolling body compartments. Despite promising aspects, DC-based immunotherapy faces challenges that include limited availability, immune escape in tumors, immunosuppression in the tumor microenvironment, and the need for effective combination therapies. A further limitation in DC-based immunotherapy is the low population of migratory DC (around 5%–10%) that migrate to lymph nodes (LNs) through afferent lymphatics depending on the LN draining site. By increasing the population of migratory DCs, DC-based immunotherapy could enhance immunotherapeutic effects on target diseases. This paper reviews the importance of DC migration and current research progress in the context of DC-based immunotherapy.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"50 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martina Libera, Valeria Caputo, Giulia Laterza, Louiza Moudoud, Alessio Soggiu, Luigi Bonizzi, Roberta A. Diotti
Ever since its discovery, human immunodeficiency virus type 1 (HIV-1) infection has remained a significant public health concern. The number of HIV-1 seropositive individuals currently stands at 40.1 million, yet definitive treatment for the virus is still unavailable on the market. Vaccination has proven to be a potent tool in combating infectious diseases, as evidenced by its success against other pathogens. However, despite ongoing efforts and research, the unique viral characteristics have prevented the development of an effective anti-HIV-1 vaccine. In this review, we aim to provide an historical overview of the various approaches attempted to create an effective anti-HIV-1 vaccine. Our objective is to explore the reasons why specific methods have failed to induce a protective immune response and to analyze the different modalities of immunogen presentation. This trial is registered with NCT05414786, NCT05471076, NCT04224701, and NCT01937455.
{"title":"The Question of HIV Vaccine: Why Is a Solution Not Yet Available?","authors":"Martina Libera, Valeria Caputo, Giulia Laterza, Louiza Moudoud, Alessio Soggiu, Luigi Bonizzi, Roberta A. Diotti","doi":"10.1155/2024/2147912","DOIUrl":"https://doi.org/10.1155/2024/2147912","url":null,"abstract":"Ever since its discovery, human immunodeficiency virus type 1 (HIV-1) infection has remained a significant public health concern. The number of HIV-1 seropositive individuals currently stands at 40.1 million, yet definitive treatment for the virus is still unavailable on the market. Vaccination has proven to be a potent tool in combating infectious diseases, as evidenced by its success against other pathogens. However, despite ongoing efforts and research, the unique viral characteristics have prevented the development of an effective anti-HIV-1 vaccine. In this review, we aim to provide an historical overview of the various approaches attempted to create an effective anti-HIV-1 vaccine. Our objective is to explore the reasons why specific methods have failed to induce a protective immune response and to analyze the different modalities of immunogen presentation. This trial is registered with NCT05414786, NCT05471076, NCT04224701, and NCT01937455.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"90 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xudong Sang, Tian Gan, Gai Ge, Dan Li, Youming Mei, Chun Pan, Siyu Long, Bibo Xie, Xiaobing Yu, Zhiming Chen, Hongsheng Wang
Background. Psoriasis, a systemic disorder mediated by the immune system, can appear on the skin, joints, or both. Individuals with cutaneous psoriasis (PsC) have an elevated risk of developing psoriatic arthritis (PsA) during their lifetime. Despite this known association, the cellular and molecular mechanisms underlying this progression remain unclear. Methods. We performed high-dimensional, in-depth immunophenotyping of peripheral blood mononuclear cells (PBMCs) in patients with PsA and psoriasis vulgaris (PsV) by mass cytometry. Blood samples were collected before and after therapy for a longitudinal study. Then three sets of comparisons were made here: active PsA vs. active PsV, untreated PsV vs. treated PsV, and untreated PsA vs. treated PsA. Results. Marked differences were observed in multiple lymphocyte subsets of PsA related to PsV, with expansion of CD4+ T cells, CD16− NK cells, and B cells. Notably, two critical markers, CD28 and CD127, specifically differentiated PsA from PsV. The expression levels of CD28 and CD127 on both Naïve T cells (TN) and central memory CD4+ T cells (TCM) were considerably higher in PsA than PsV. Meanwhile, after treatment, patients with PsV had higher levels of CD28hi CD127hi CD4+ TCM cells, CD28hi CD127hi CD4+ TN cells, and CD16− NK cells. Conclusion. In the circulation of PsA patients, the TN and CD4+ TCM are characterized with more abundant CD28 and CD127, which effectively distinguished PsA from PsV. This may indicate that individuals undergoing PsV could be stratified at high risk of developing PsA based on the circulating levels of CD28 and CD127 on specific cell subsets.
{"title":"Circulating Immune Landscape Profiling in Psoriasis Vulgaris and Psoriatic Arthritis by Mass Cytometry","authors":"Xudong Sang, Tian Gan, Gai Ge, Dan Li, Youming Mei, Chun Pan, Siyu Long, Bibo Xie, Xiaobing Yu, Zhiming Chen, Hongsheng Wang","doi":"10.1155/2024/9927964","DOIUrl":"https://doi.org/10.1155/2024/9927964","url":null,"abstract":"<i>Background</i>. Psoriasis, a systemic disorder mediated by the immune system, can appear on the skin, joints, or both. Individuals with cutaneous psoriasis (PsC) have an elevated risk of developing psoriatic arthritis (PsA) during their lifetime. Despite this known association, the cellular and molecular mechanisms underlying this progression remain unclear. <i>Methods</i>. We performed high-dimensional, in-depth immunophenotyping of peripheral blood mononuclear cells (PBMCs) in patients with PsA and psoriasis vulgaris (PsV) by mass cytometry. Blood samples were collected before and after therapy for a longitudinal study. Then three sets of comparisons were made here: active PsA <i>vs</i>. active PsV, untreated PsV <i>vs</i>. treated PsV, and untreated PsA <i>vs</i>. treated PsA. <i>Results</i>. Marked differences were observed in multiple lymphocyte subsets of PsA related to PsV, with expansion of CD4<sup>+</sup> T cells, CD16<sup>−</sup> NK cells, and B cells. Notably, two critical markers, CD28 and CD127, specifically differentiated PsA from PsV. The expression levels of CD28 and CD127 on both Naïve T cells (T<sub>N</sub>) and central memory CD4<sup>+</sup> T cells (T<sub>CM</sub>) were considerably higher in PsA than PsV. Meanwhile, after treatment, patients with PsV had higher levels of CD28<sup>hi</sup> CD127<sup>hi</sup> CD4<sup>+</sup> T<sub>CM</sub> cells, CD28<sup>hi</sup> CD127<sup>hi</sup> CD4<sup>+</sup> T<sub>N</sub> cells, and CD16<sup>−</sup> NK cells. <i>Conclusion</i>. In the circulation of PsA patients, the T<sub>N</sub> and CD4<sup>+</sup> T<sub>CM</sub> are characterized with more abundant CD28 and CD127, which effectively distinguished PsA from PsV. This may indicate that individuals undergoing PsV could be stratified at high risk of developing PsA based on the circulating levels of CD28 and CD127 on specific cell subsets.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"84 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingyi Yang, Yani Su, Ke Xu, Haishi Zheng, Yongsong Cai, Pengfei Wen, Zhi Yang, Lin Liu, Peng Xu
<i>Objective</i>. Osteosarcoma (OS) represents a prevalent primary bone neoplasm predominantly affecting the pediatric and adolescent populations, presenting a considerable challenge to human health. The objective of this investigation is to develop a prognostic model centered on anoikis-related genes (ARGs), with the aim of accurately forecasting the survival outcomes of individuals diagnosed with OS and offering insights into modulating the immune microenvironment. <i>Methods</i>. The study’s training cohort comprised 86 OS patients sourced from The Cancer Genome Atlas database, while the validation cohort consisted of 53 OS patients extracted from the Gene Expression Omnibus database. Differential analysis utilized the GSE33382 dataset, encompassing three normal samples and 84 OS samples. Subsequently, the study executed gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses. Identification of differentially expressed ARGs associated with OS prognosis was carried out through univariate COX regression analysis, followed by LASSO regression analysis to mitigate overfitting risks and construct a robust prognostic model. Model accuracy was assessed via risk curves, survival curves, receiver operating characteristic curves, independent prognostic analysis, principal component analysis, and t-distributed stochastic neighbor embedding (t-SNE) analysis. Additionally, a nomogram model was devised, exhibiting promising potential in predicting OS patient prognosis. Further investigations incorporated gene set enrichment analysis to delineate active pathways in high- and low-risk groups. Furthermore, the impact of the risk prognostic model on the immune microenvironment of OS was evaluated through tumor microenvironment analysis, single-sample gene set enrichment analysis (ssGSEA), and immune infiltration cell correlation analysis. Drug sensitivity analysis was conducted to identify potentially effective drugs for OS treatment. Ultimately, the verification of the implicated ARGs in the model construction was conducted through the utilization of real-time quantitative polymerase chain reaction (RT-qPCR). <i>Results</i>. The ARGs risk prognostic model was developed, comprising seven high-risk ARGs (CBS, MYC, MMP3, CD36, SCD, COL13A1, and HSP90B1) and four low-risk ARGs (VASH1, TNFRSF1A, PIP5K1C, and CTNNBIP1). This prognostic model demonstrates a robust capability in predicting overall survival among patients. Analysis of immune correlations revealed that the high-risk group exhibited lower immune scores compared to the low-risk group within our prognostic model. Specifically, CD8+ T cells, neutrophils, and tumor-infiltrating lymphocytes were notably downregulated in the high-risk group, alongside significant downregulation of checkpoint and T cell coinhibition mechanisms. Additionally, three immune checkpoint-related genes (CD200R1, HAVCR2, and LAIR1) displayed significant differences between the high- and low-risk groups. The utiliz
目的。骨肉瘤（Osteosarcoma，OS）是一种流行的原发性骨肿瘤，主要影响儿童和青少年群体，给人类健康带来了巨大挑战。这项研究的目的是开发一个以anoikis相关基因（ARGs）为中心的预后模型，旨在准确预测被诊断为骨肉瘤患者的生存结果，并为调节免疫微环境提供见解。研究方法该研究的训练队列由来自癌症基因组图谱（The Cancer Genome Atlas）数据库的86名OS患者组成，而验证队列由来自基因表达总库（Gene Expression Omnibus）数据库的53名OS患者组成。差异分析利用了GSE33382数据集，其中包括3个正常样本和84个OS样本。随后，研究人员进行了基因本体和京都基因与基因组百科全书的富集分析。通过单变量COX回归分析鉴定与OS预后相关的差异表达ARGs，然后进行LASSO回归分析以降低过拟合风险并构建稳健的预后模型。通过风险曲线、生存曲线、接收者操作特征曲线、独立预后分析、主成分分析和 t 分布随机邻域嵌入（t-SNE）分析评估了模型的准确性。此外，还设计了一个提名图模型，该模型在预测 OS 患者预后方面表现出了良好的潜力。进一步的研究纳入了基因组富集分析，以划分高风险组和低风险组的活跃通路。此外，还通过肿瘤微环境分析、单样本基因组富集分析（ssGSEA）和免疫浸润细胞相关性分析，评估了风险预后模型对 OS 免疫微环境的影响。还进行了药物敏感性分析，以确定治疗 OS 的潜在有效药物。最后，利用实时定量聚合酶链反应（RT-qPCR）对模型构建中涉及的 ARGs 进行了验证。结果。建立的ARGs风险预后模型包括7个高风险ARGs（CBS、MYC、MMP3、CD36、SCD、COL13A1和HSP90B1）和4个低风险ARGs（VASH1、TNFRSF1A、PIP5K1C和CTNNBIP1）。该预后模型在预测患者总生存期方面表现出了强大的能力。免疫相关性分析表明，在我们的预后模型中，高风险组的免疫评分低于低风险组。具体来说，CD8+ T 细胞、中性粒细胞和肿瘤浸润淋巴细胞在高风险组明显下调，同时检查点和 T 细胞联合抑制机制也显著下调。此外，三个免疫检查点相关基因（CD200R1、HAVCR2 和 LAIR1）在高风险组和低风险组之间存在显著差异。利用提名图模型预测 OS 患者的预后效果显著。此外，肿瘤转移也是一个独立的预后因素，表明ARGs与OS转移之间存在潜在联系。值得注意的是，我们的研究发现硼替佐米、米多司林、CHIR.99021、JNK.Inhibitor.VIII、来那度胺、舒尼替尼、GDC0941和GW.441756这八种药物对OS具有敏感性。RT-qPCR 研究结果表明，在 OS 中，CBS、MYC、MMP3 和 PIP5K1C 的表达水平降低。相反，在 OS 中观察到 CD36、SCD、COL13A1、HSP90B1、VASH1 和 CTNNBIP1 的表达水平升高。结论这项调查的结果为预测确诊为 OS 患者的生存结果提供了机会。此外，这些研究结果还有望推动有关这一特殊疾病的预后评估和治疗干预的研究工作。
{"title":"Develop a Novel Signature to Predict the Survival and Affect the Immune Microenvironment of Osteosarcoma Patients: Anoikis-Related Genes","authors":"Mingyi Yang, Yani Su, Ke Xu, Haishi Zheng, Yongsong Cai, Pengfei Wen, Zhi Yang, Lin Liu, Peng Xu","doi":"10.1155/2024/6595252","DOIUrl":"https://doi.org/10.1155/2024/6595252","url":null,"abstract":"<i>Objective</i>. Osteosarcoma (OS) represents a prevalent primary bone neoplasm predominantly affecting the pediatric and adolescent populations, presenting a considerable challenge to human health. The objective of this investigation is to develop a prognostic model centered on anoikis-related genes (ARGs), with the aim of accurately forecasting the survival outcomes of individuals diagnosed with OS and offering insights into modulating the immune microenvironment. <i>Methods</i>. The study’s training cohort comprised 86 OS patients sourced from The Cancer Genome Atlas database, while the validation cohort consisted of 53 OS patients extracted from the Gene Expression Omnibus database. Differential analysis utilized the GSE33382 dataset, encompassing three normal samples and 84 OS samples. Subsequently, the study executed gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses. Identification of differentially expressed ARGs associated with OS prognosis was carried out through univariate COX regression analysis, followed by LASSO regression analysis to mitigate overfitting risks and construct a robust prognostic model. Model accuracy was assessed via risk curves, survival curves, receiver operating characteristic curves, independent prognostic analysis, principal component analysis, and t-distributed stochastic neighbor embedding (t-SNE) analysis. Additionally, a nomogram model was devised, exhibiting promising potential in predicting OS patient prognosis. Further investigations incorporated gene set enrichment analysis to delineate active pathways in high- and low-risk groups. Furthermore, the impact of the risk prognostic model on the immune microenvironment of OS was evaluated through tumor microenvironment analysis, single-sample gene set enrichment analysis (ssGSEA), and immune infiltration cell correlation analysis. Drug sensitivity analysis was conducted to identify potentially effective drugs for OS treatment. Ultimately, the verification of the implicated ARGs in the model construction was conducted through the utilization of real-time quantitative polymerase chain reaction (RT-qPCR). <i>Results</i>. The ARGs risk prognostic model was developed, comprising seven high-risk ARGs (CBS, MYC, MMP3, CD36, SCD, COL13A1, and HSP90B1) and four low-risk ARGs (VASH1, TNFRSF1A, PIP5K1C, and CTNNBIP1). This prognostic model demonstrates a robust capability in predicting overall survival among patients. Analysis of immune correlations revealed that the high-risk group exhibited lower immune scores compared to the low-risk group within our prognostic model. Specifically, CD8+ T cells, neutrophils, and tumor-infiltrating lymphocytes were notably downregulated in the high-risk group, alongside significant downregulation of checkpoint and T cell coinhibition mechanisms. Additionally, three immune checkpoint-related genes (CD200R1, HAVCR2, and LAIR1) displayed significant differences between the high- and low-risk groups. The utiliz","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140311634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nonhuman primates are an important experimental model for the development of targeted biological therapeutics because of their immunological closeness to humans. However, there are very few antibody reagents relevant for delineating the different immune cell subsets based on nonhuman primate antigens directly or with cross-reactivity to those in humans. Here, we report specific expression of HLA-DR, PD-1, and CD123 on different circulating immune cell subsets in the peripheral blood that included T cells (CD3+), T cells subsets (CD4+ and CD8+), B cells (CD20+), natural killer (NK) cells (CD3–CD16+), and natural killer T cells (CD3+CD16+) along with different monocyte subsets in squirrel monkey (Saimiri sciureus). We established cross-reactivity of commercial mouse antihuman monoclonal antibodies (mAbs), with these various immune cell surface markers. These findings should aid further future comprehensive understanding of the immune parameters and identification of new biomarkers to significantly improve SQM as a model for biomedical studies.
非人灵长类动物在免疫学上与人类非常接近，因此是开发靶向生物疗法的重要实验模型。然而，很少有抗体试剂能直接根据非人灵长类动物的抗原或与人类具有交叉反应性的抗原来划分不同的免疫细胞亚群。在这里，我们报告了 HLA-DR、PD-1 和 CD123 在松鼠猴（Saimiri sciureus）外周血中不同循环免疫细胞亚群上的特异性表达，这些亚群包括 T 细胞（CD3+）、T 细胞亚群（CD4+ 和 CD8+）、B 细胞（CD20+）、自然杀伤（NK）细胞（CD3-CD16+）和自然杀伤 T 细胞（CD3+CD16+）以及不同的单核细胞亚群。我们确定了商用小鼠抗人单克隆抗体（mAbs）与这些不同免疫细胞表面标志物的交叉反应性。这些发现将有助于今后进一步全面了解免疫参数和鉴定新的生物标记物，从而大大提高松鼠猴作为生物医学研究模型的水平。
{"title":"Identification of Specific Cell Surface Markers on Immune Cells of Squirrel Monkeys (Saimiri sciureus)","authors":"Bharti P. Nehete, Ashley DeLise, Pramod N. Nehete","doi":"10.1155/2024/8215195","DOIUrl":"https://doi.org/10.1155/2024/8215195","url":null,"abstract":"Nonhuman primates are an important experimental model for the development of targeted biological therapeutics because of their immunological closeness to humans. However, there are very few antibody reagents relevant for delineating the different immune cell subsets based on nonhuman primate antigens directly or with cross-reactivity to those in humans. Here, we report specific expression of HLA-DR, PD-1, and CD123 on different circulating immune cell subsets in the peripheral blood that included T cells (CD3+), T cells subsets (CD4+ and CD8+), B cells (CD20+), natural killer (NK) cells (CD3–CD16+), and natural killer T cells (CD3+CD16+) along with different monocyte subsets in squirrel monkey (<i>Saimiri sciureus</i>). We established cross-reactivity of commercial mouse antihuman monoclonal antibodies (mAbs), with these various immune cell surface markers. These findings should aid further future comprehensive understanding of the immune parameters and identification of new biomarkers to significantly improve SQM as a model for biomedical studies.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"3 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140300612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiangting Bu, Ming Wang, Jing Yuan, Jing Song, Ge Luan, Jiaqi Yu, Yang Wang, Ying Li, Chengshuo Wang, Luo Zhang
Background. Serine proteinase inhibitors, clade B, member 3 (SerpinB3) and B4 are highly similar in amino acid sequences and associated with inflammation regulation. We investigated SerpinB3 and B4 expression and their roles in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods. The expression of SerpinB3 and B4 in nasal mucosa tissues, brush cells, and secretions from CRSwNP patients was measured, and their regulation by inflammatory cytokines were investigated. Their functions were also analyzed using air–liquid interface (ALI)-cultured primary human nasal epithelial cells (HNECs) and transcriptomic analysis. Results. Both SerpinB3 and B4 expression was higher in nasal mucosa, brush cells, and secretions from eosinophilic (E) CRSwNP and nonECRSwNP patients than in healthy controls. Immunofluorescence staining indicated that SerpinB3 and B4 were primarily expressed in epithelial cells and their expression was higher in CRSwNP patients. SerpinB3 and B4 expression was upregulated by interleukin-4 (IL-4), IL-5, IL-6, and IL-17a. Transcriptomic analysis identified differentially expressed genes (DEGs) in response to recombinant SerpinB3 and B4 stimulation. Both the DEGs of SerpinB3 and B4 were associated with disease genes of nasal polyps and inflammation in DisGeNET database. Pathway enrichment indicated that downregulated DEGs of SerpinB3 and B4 were both enriched in cytokine–cytokine receptor interactions, with CXCL8 as the hub gene in the protein–protein interaction networks. Furthermore, CXCL8/IL-8 expression was downregulated by recombinant SerpinB3 and B4 protein in ALI-cultured HNECs, and upregulated when knockdown of SerpinB3/B4. Conclusion. SerpinB3/B4 expression is upregulated in nasal mucosa of CRSwNP patients. SerpinB3/B4 may play an anti-inflammatory role in CRSwNP by inhibiting the expression of epithelial cell-derived CXCL8/IL-8.
{"title":"SerpinB3/B4 Abates Epithelial Cell-Derived CXCL8/IL-8 Expression in Chronic Rhinosinusitis with Nasal Polyps","authors":"Xiangting Bu, Ming Wang, Jing Yuan, Jing Song, Ge Luan, Jiaqi Yu, Yang Wang, Ying Li, Chengshuo Wang, Luo Zhang","doi":"10.1155/2024/8553447","DOIUrl":"https://doi.org/10.1155/2024/8553447","url":null,"abstract":"<i>Background</i>. Serine proteinase inhibitors, clade B, member 3 (SerpinB3) and B4 are highly similar in amino acid sequences and associated with inflammation regulation. We investigated SerpinB3 and B4 expression and their roles in chronic rhinosinusitis with nasal polyps (CRSwNP). <i>Methods</i>. The expression of SerpinB3 and B4 in nasal mucosa tissues, brush cells, and secretions from CRSwNP patients was measured, and their regulation by inflammatory cytokines were investigated. Their functions were also analyzed using air–liquid interface (ALI)-cultured primary human nasal epithelial cells (HNECs) and transcriptomic analysis. <i>Results</i>. Both SerpinB3 and B4 expression was higher in nasal mucosa, brush cells, and secretions from eosinophilic (E) CRSwNP and nonECRSwNP patients than in healthy controls. Immunofluorescence staining indicated that SerpinB3 and B4 were primarily expressed in epithelial cells and their expression was higher in CRSwNP patients. SerpinB3 and B4 expression was upregulated by interleukin-4 (IL-4), IL-5, IL-6, and IL-17a. Transcriptomic analysis identified differentially expressed genes (DEGs) in response to recombinant SerpinB3 and B4 stimulation. Both the DEGs of SerpinB3 and B4 were associated with disease genes of nasal polyps and inflammation in DisGeNET database. Pathway enrichment indicated that downregulated DEGs of SerpinB3 and B4 were both enriched in cytokine–cytokine receptor interactions, with CXCL8 as the hub gene in the protein–protein interaction networks. Furthermore, CXCL8/IL-8 expression was downregulated by recombinant SerpinB3 and B4 protein in ALI-cultured HNECs, and upregulated when knockdown of SerpinB3/B4. <i>Conclusion</i>. SerpinB3/B4 expression is upregulated in nasal mucosa of CRSwNP patients. SerpinB3/B4 may play an anti-inflammatory role in CRSwNP by inhibiting the expression of epithelial cell-derived CXCL8/IL-8.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"24 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140201484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A decline in immune response, exhibited in the form of immunosenescence and inflammaging, is an age-associated disturbance of the immune system known to predispose the elderly to a greater susceptibility to infection and poor vaccine response. Polysaccharides and polyphenols from botanicals are known for their immune modulation effects. Here we evaluated a standardized mushroom-based composition, UP360, from Aloe barbadensis, Poria cocos, and Rosmarinus officinalis, as a natural nutritional supplement for a balanced immune response in an accelerated aging mouse model. Immunosenescence was induced by continual subcutaneous injection of D-galactose (D-gal) at a dose of 500 mg/kg/day to CD-1 mice. UP360 was administered at oral doses of 200 and 400 mg/kg to the mice starting on the 5th week of D-gal injection. The study lasted for a total of 9 weeks. All mice were given a quadrivalent influenza vaccine at 3 µg/animal via intramuscular injection 14 days before the end of the study. A group of D-gal-treated mice treated at 400 mg/kg/day UP360 was kept without vaccination. Whole blood, serum, spleen homogenate, and thymus tissues were used for analysis. UP360 was found to improve the immune response as evidenced by stimulation of innate and adaptive immune responses, increase antioxidant capacity as reflected by augmented SOD and Nrf2, and preserve vital immune organs, such as the thymus, from aging-associated damage. The findings depicted in this report show the effect of the composition in activating and maintaining homeostasis of the immune system both during active infections and as a preventive measure to help prime the immune system. These data warrant further clinical study to explore the potential application of the mushroom-based composition as an adjunct nutritional supplement for a balanced immune response.
{"title":"An Aloe-Based Composition Constituting Polysaccharides and Polyphenols Protected Mice against D-Galactose-Induced Immunosenescence","authors":"Mesfin Yimam, Teresa Horm, Alexandria O’Neal, Ping Jiao, Mei Hong, Qi Jia","doi":"10.1155/2024/9307906","DOIUrl":"https://doi.org/10.1155/2024/9307906","url":null,"abstract":"A decline in immune response, exhibited in the form of immunosenescence and inflammaging, is an age-associated disturbance of the immune system known to predispose the elderly to a greater susceptibility to infection and poor vaccine response. Polysaccharides and polyphenols from botanicals are known for their immune modulation effects. Here we evaluated a standardized mushroom-based composition, UP360, from <i>Aloe barbadensis</i>, <i>Poria co</i>cos, and <i>Rosmarinus officinalis</i>, as a natural nutritional supplement for a balanced immune response in an accelerated aging mouse model. Immunosenescence was induced by continual subcutaneous injection of <small>D</small>-galactose (<small>D</small>-gal) at a dose of 500 mg/kg/day to CD-1 mice. UP360 was administered at oral doses of 200 and 400 mg/kg to the mice starting on the 5<sup>th</sup> week of <small>D</small>-gal injection. The study lasted for a total of 9 weeks. All mice were given a quadrivalent influenza vaccine at 3 <i>µ</i>g/animal via intramuscular injection 14 days before the end of the study. A group of <small>D</small>-gal-treated mice treated at 400 mg/kg/day UP360 was kept without vaccination. Whole blood, serum, spleen homogenate, and thymus tissues were used for analysis. UP360 was found to improve the immune response as evidenced by stimulation of innate and adaptive immune responses, increase antioxidant capacity as reflected by augmented SOD and Nrf2, and preserve vital immune organs, such as the thymus, from aging-associated damage. The findings depicted in this report show the effect of the composition in activating and maintaining homeostasis of the immune system both during active infections and as a preventive measure to help prime the immune system. These data warrant further clinical study to explore the potential application of the mushroom-based composition as an adjunct nutritional supplement for a balanced immune response.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"104 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140128861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jean-Nicolas Boursiquot, Hugo Chapdelaine, Charles St-Pierre, Jacques Hébert
Background. Limited data are available on the clinical profile and disease burden of hereditary angioedema (HAE) in Canadians. Objective. This study aimed to assess HAE disease characteristics and the burden of disease in Canadians with HAE types I, II, and normal levels of C1 inhibitor (nC1-INH). Materials and Methods. A 46-item patient survey evaluating clinical characteristics and burden of disease was developed and disseminated by the HAE patient organization Angio-oédeme héréditaire du Québec in Quebec, Canada, from May 2019 to February 2020. The survey received Research Review Board ethics approval. Results. In the 35 respondents, HAE type I was the most common (46%), followed by nC1-INH (43%). Female participants were significantly younger at first symptom presentation than males (). Prior to diagnosis, 69% of participants underwent unnecessary treatments and procedures, with a 10-year delay between first symptoms and diagnosis. Before starting the current treatment, 42% of participants experienced weekly HAE attacks. Most participants identified experiencing attacks in the abdomen (89%), followed by the larynx (66%), feet (66%), hands (63%), and face (63%). Most attacks were severe or moderate, yet almost half of patients waited >1 hr before getting medical attention at their last emergency department (ED) visit. HAE was associated with decreased health-related quality of life, leading to significant functional impairment in personal and professional life. As compared to HAE type I/II, patients with HAE nC1-INH were treated more often with tranexamic acid for long-term prophylaxis, and their condition was less controlled, resulting in more attacks and ED visits. Conclusion. HAE manifests in this patient population as frequent moderate-to-severe attacks and a high disease burden; the HAE subtype may differentially affect care requirements. There is an urgent need for increased awareness and education on HAE among treating physicians.
背景。有关加拿大人遗传性血管性水肿（HAE）的临床概况和疾病负担的数据十分有限。目的。本研究旨在评估患有 HAE I 型、II 型和 C1 抑制剂（nC1-INH）水平正常的加拿大人的 HAE 疾病特征和疾病负担。材料与方法。HAE 患者组织 Angio-oédeme héréditaire du Québec 于 2019 年 5 月至 2020 年 2 月在加拿大魁北克省开展并传播了一项包含 46 个项目的患者调查，以评估临床特征和疾病负担。调查获得了研究审查委员会的伦理批准。调查结果显示在 35 名受访者中，最常见的是 HAE I 型（46%），其次是 nC1-INH（43%）。女性受访者首次出现症状时的年龄明显小于男性（）。在确诊之前，69% 的参与者接受了不必要的治疗和手术，从首次出现症状到确诊之间的时间延迟了 10 年。在开始目前的治疗之前，42% 的参与者每周都会发作一次 HAE。大多数参与者认为发作部位在腹部（89%），其次是喉部（66%）、足部（66%）、手部（63%）和面部（63%）。大多数发作为重度或中度，但几乎有一半的患者在最后一次去急诊科（ED）就诊时等待了>1小时才得到治疗。HAE与健康相关的生活质量下降有关，导致个人和职业生活功能严重受损。与HAE I/II型相比，HAE nC1-INH型患者更常使用氨甲环酸进行长期预防性治疗，但病情控制较差，导致发作次数和急诊就诊次数增加。结论HAE在这一患者群体中表现为频繁的中重度发作和较高的疾病负担；HAE亚型可能会对护理要求产生不同的影响。治疗医生迫切需要加强对 HAE 的认识和教育。
{"title":"The Disease Burden of Hereditary Angioedema: Insights from a Survey in French-Canadians from Quebec","authors":"Jean-Nicolas Boursiquot, Hugo Chapdelaine, Charles St-Pierre, Jacques Hébert","doi":"10.1155/2024/3028617","DOIUrl":"https://doi.org/10.1155/2024/3028617","url":null,"abstract":"<i>Background</i>. Limited data are available on the clinical profile and disease burden of hereditary angioedema (HAE) in Canadians. <i>Objective</i>. This study aimed to assess HAE disease characteristics and the burden of disease in Canadians with HAE types I, II, and normal levels of C1 inhibitor (nC1-INH). <i>Materials and Methods</i>. A 46-item patient survey evaluating clinical characteristics and burden of disease was developed and disseminated by the HAE patient organization <i>Angio-oédeme héréditaire du Québec</i> in Quebec, Canada, from May 2019 to February 2020. The survey received Research Review Board ethics approval. <i>Results</i>. In the 35 respondents, HAE type I was the most common (46%), followed by nC1-INH (43%). Female participants were significantly younger at first symptom presentation than males (<span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"></path></g></svg><span></span><span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 21.921 11.7782\" width=\"21.921pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"></path></g></svg>).</span></span> Prior to diagnosis, 69% of participants underwent unnecessary treatments and procedures, with a 10-year delay between first symptoms and diagnosis. Before starting the current treatment, 42% of participants experienced weekly HAE attacks. Most participants identified experiencing attacks in the abdomen (89%), followed by the larynx (66%), feet (66%), hands (63%), and face (63%). Most attacks were severe or moderate, yet almost half of patients waited >1 hr before getting medical attention at their last emergency department (ED) visit. HAE was associated with decreased health-related quality of life, leading to significant functional impairment in personal and professional life. As compared to HAE type I/II, patients with HAE nC1-INH were treated more often with tranexamic acid for long-term prophylaxis, and their condition was less controlled, resulting in more attacks and ED visits. <i>Conclusion</i>. HAE manifests in this patient population as frequent moderate-to-severe attacks and a high disease burden; the HAE subtype may differentially affect care requirements. There is an urgent need for increased awareness and education on HAE among treating physicians.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"45 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140057723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose. NLRP3-associated autoinflammatory disease (NLRP3-AID) is characterized by gain-of-function variants in the NLRP3 gene. Since there are little literature focusing on pediatric NLRP3-AID in China, we aimed to elucidate the phenotypic and genotypic profiles of Chinese patients with NLRP3-AID. Methods. Patients with NLRP3-AID at three rheumatology centers in China were genotyped through whole exome sequencing or gene panel sequencing. Sanger sequencing was performed on all patients and their parents. Clinical phenotype, treatment, and prognosis were analyzed. Results. Nine patients with NLRP3-AID were enrolled between December 2014 and October 2022 with an average follow-up period exceeding 30 months. The median age of onset was 12 months, and 66.7% were younger than 3 years old. The diagnosis was significantly delayed and the median delay duration was 115 months. The patients most commonly presented with rash (100%), arthritis/arthralgia (88.9%), lymphadenopathy (88.9%), fever (77.8%), and growth retardation (44.4%). During acute attack, white blood cell, C-reactive protein, and/or erythrocyte sedimentation rate all increased in all cases, and inflammatory markers remained elevated beyond 7 days postfever resolution in 57.1% of patients (4/7). Two cases of chronic infantile neurological cutaneous articular syndrome (CINCA) had clubbed fingers, one with interstitial lung disease, a finding rarely reported. Treatment with glucocorticoids (77.8%) and biologic agents (33.3%) yielded 66% complete remission and 33% partial remission. Genetic analysis identified eight pathogenic NLRP3 missense mutations, including one novel mutation. Conclusions. Our study illuminated the distinct clinical and genetic features of Chinese NLRP3-AID patients, emphasizing the significance of early genetic screening. Despite delayed diagnosis, treatment primarily with glucocorticoids and biologic agents, led to favorable outcomes. Genetic heterogeneity, including a novel mutation, highlighted the complexity of NLRP3-AID in this population.
{"title":"Clinical and Genetic Spectrum of Nine Cases of NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) and Identification of One Novel NLRP3 Mutation by Genetic Variation Analyses","authors":"Yaoyao Shangguan, Xingru Ding, Le Ma, Yi-Xin Cai, Shulei Xiang, Xiu-Feng Huang, Yunyan Shen, Hai-Guo Yu, Wenjie Zheng","doi":"10.1155/2024/5722548","DOIUrl":"https://doi.org/10.1155/2024/5722548","url":null,"abstract":"<i>Purpose</i>. NLRP3-associated autoinflammatory disease (NLRP3-AID) is characterized by gain-of-function variants in the NLRP3 gene. Since there are little literature focusing on pediatric NLRP3-AID in China, we aimed to elucidate the phenotypic and genotypic profiles of Chinese patients with NLRP3-AID. <i>Methods</i>. Patients with NLRP3-AID at three rheumatology centers in China were genotyped through whole exome sequencing or gene panel sequencing. Sanger sequencing was performed on all patients and their parents. Clinical phenotype, treatment, and prognosis were analyzed. <i>Results</i>. Nine patients with NLRP3-AID were enrolled between December 2014 and October 2022 with an average follow-up period exceeding 30 months. The median age of onset was 12 months, and 66.7% were younger than 3 years old. The diagnosis was significantly delayed and the median delay duration was 115 months. The patients most commonly presented with rash (100%), arthritis/arthralgia (88.9%), lymphadenopathy (88.9%), fever (77.8%), and growth retardation (44.4%). During acute attack, white blood cell, C-reactive protein, and/or erythrocyte sedimentation rate all increased in all cases, and inflammatory markers remained elevated beyond 7 days postfever resolution in 57.1% of patients (4/7). Two cases of chronic infantile neurological cutaneous articular syndrome (CINCA) had clubbed fingers, one with interstitial lung disease, a finding rarely reported. Treatment with glucocorticoids (77.8%) and biologic agents (33.3%) yielded 66% complete remission and 33% partial remission. Genetic analysis identified eight pathogenic NLRP3 missense mutations, including one novel mutation. <i>Conclusions</i>. Our study illuminated the distinct clinical and genetic features of Chinese NLRP3-AID patients, emphasizing the significance of early genetic screening. Despite delayed diagnosis, treatment primarily with glucocorticoids and biologic agents, led to favorable outcomes. Genetic heterogeneity, including a novel mutation, highlighted the complexity of NLRP3-AID in this population.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"73 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140045277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vera S. Ruzanova, Svetlana S. Kirikovich, Evgeniy V. Levites, Anastasia S. Proskurina, Evgeniya V. Dolgova, Genrikh S. Ritter, Yaroslav R. Efremov, Tatyana D. Dubatolova, Alexander V. Sysoev, Danil I. Koleno, Alexandr A. Ostanin, Elena R. Chernykh, Sergey S. Bogachev
Macrophages are the immune cells of high-immunological plasticity, which can exert both pro- and anti-inflammatory activity, as well as repolarize their phenotype to the opposite or neutral one. In this regard, M2 macrophages of the tumor-associated stroma (TAS) are a promising therapeutic target in treating malignant neoplasms. Using FACS assay, we have estimated the CD11b+/Ly-6G+/Ly-6C+ fraction of macrophages from the peritoneum and TAS in intact healthy mice and those with developed Lewis carcinoma, both untreated and treated according to Karanahan technology in combination with group-specific macrophage activator (GcMAF-RF). As well, the pattern of pro- and anti-inflammatory cytokines mRNA expression in different groups of experimental and tumor-bearing animals was assessed. It was found that: (i) exposure of intact mice to GcMAF-RF results in the increased number of CD11b+/Ly-6C+ peritoneal macrophages and, at the same time, the expression pattern of cytokines in peritoneal macrophages switches from that characteristic of the mixed M1/M2 phenotype to that characteristic of the neutral M0 one; (ii) combination of Karanahan technology and GcMAF-RF treatment results in M0/M1 repolarization of TAS macrophages; (iii) in tumor-bearing mice, the response of peritoneal macrophages to such a treatment is associated with the induction of anti-inflammatory reaction, which is opposite to that in TAS macrophages.
巨噬细胞是具有高度免疫可塑性的免疫细胞，既能发挥促炎活性，也能发挥抗炎活性，还能将其表型重新极化为相反或中性的表型。在这方面，肿瘤相关基质（TAS）的M2巨噬细胞是治疗恶性肿瘤的一个很有前景的治疗靶点。我们使用 FACS 分析法估算了未经处理或根据卡拉纳汉技术结合组特异性巨噬细胞激活剂（GcMAF-RF）处理的完整健康小鼠和患 Lewis 癌小鼠腹膜和 TAS 中巨噬细胞的 CD11b+/Ly-6G+/Ly-6C+ 部分。此外，还评估了不同组实验动物和肿瘤动物体内促炎和抗炎细胞因子 mRNA 的表达模式。研究发现(i) 将完整的小鼠暴露于 GcMAF-RF 会导致 CD11b+/Ly-6C+ 腹膜巨噬细胞的数量增加，同时，腹膜巨噬细胞中细胞因子的表达模式会从 M1/M2 混合表型转变为中性 M0 表型；(ii) 结合使用 Karanahan 技术和 GcMAF-RF 处理，可使 TAS 巨噬细胞发生 M0/M1 极化；(iii) 在肿瘤小鼠中，腹腔巨噬细胞对这种处理的反应与诱导抗炎反应有关，这与 TAS 巨噬细胞的反应相反。
{"title":"The Macrophage Activator GcMAF-RF Enhances the Antitumor Effect of Karanahan Technology through Induction of M2–M1 Macrophage Reprogramming","authors":"Vera S. Ruzanova, Svetlana S. Kirikovich, Evgeniy V. Levites, Anastasia S. Proskurina, Evgeniya V. Dolgova, Genrikh S. Ritter, Yaroslav R. Efremov, Tatyana D. Dubatolova, Alexander V. Sysoev, Danil I. Koleno, Alexandr A. Ostanin, Elena R. Chernykh, Sergey S. Bogachev","doi":"10.1155/2024/7484490","DOIUrl":"https://doi.org/10.1155/2024/7484490","url":null,"abstract":"Macrophages are the immune cells of high-immunological plasticity, which can exert both pro- and anti-inflammatory activity, as well as repolarize their phenotype to the opposite or neutral one. In this regard, M2 macrophages of the tumor-associated stroma (TAS) are a promising therapeutic target in treating malignant neoplasms. Using FACS assay, we have estimated the CD11b+/Ly-6G+/Ly-6C+ fraction of macrophages from the peritoneum and TAS in intact healthy mice and those with developed Lewis carcinoma, both untreated and treated according to Karanahan technology in combination with group-specific macrophage activator (GcMAF-RF). As well, the pattern of pro- and anti-inflammatory cytokines mRNA expression in different groups of experimental and tumor-bearing animals was assessed. It was found that: (i) exposure of intact mice to GcMAF-RF results in the increased number of CD11b+/Ly-6C+ peritoneal macrophages and, at the same time, the expression pattern of cytokines in peritoneal macrophages switches from that characteristic of the mixed M1/M2 phenotype to that characteristic of the neutral M0 one; (ii) combination of Karanahan technology and GcMAF-RF treatment results in M0/M1 repolarization of TAS macrophages; (iii) in tumor-bearing mice, the response of peritoneal macrophages to such a treatment is associated with the induction of anti-inflammatory reaction, which is opposite to that in TAS macrophages.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"55 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140010068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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