Our research addresses the critical environmental issue of a fine particulate matter (PM2.5), focusing on its association with the increased infection risks. We explored the influence of PM2.5 on human beta-defensin 1 (HBD1), an essential peptide in mucosal immunity found in the airway epithelium. Using C57BL/6J mice and human bronchial epithelial cells (HBE), we examined the effects of PM2.5 exposure followed by Pseudomonas aeruginosa (P. aeruginosa) infection on HBD1 expression at both mRNA and protein levels. The study revealed that PM2.5’s toxicity to epithelial cells and animals varies with time and concentration. Notably, HBE cells exposed to PM2.5 and P. aeruginosa showed increased bacterial invasion and decreased HBD1 expression compared to the cells exposed to P. aeruginosa alone. Similarly, mice studies indicated that combined exposure to PM2.5 and P. aeruginosa significantly reduced survival rates and increased bacterial invasion. These harmful effects, however, were alleviated by administering exogenous HBD1. Furthermore, our findings highlight the activation of MAPK and NF-κB pathways following PM2.5 exposure. Inhibiting these pathways effectively increased HBD1 expression and diminished bacterial invasion. In summary, our study establishes that PM2.5 exposure intensifies P. aeruginosa invasion in both HBE cells and mouse models, primarily by suppressing HBD1 expression. This effect can be counteracted with exogenous HBD1, with the downregulation mechanism involving the MAPK and NF-κB pathways. Our study endeavors to elucidate the pathogenesis of lung infections associated with PM2.5 exposure, providing a novel theoretical basis for the development of prevention and treatment strategies, with substantial clinical significance.
{"title":"PM2.5 Causes Increased Bacterial Invasion by Affecting HBD1 Expression in the Lung","authors":"Tianqi Zheng, Yajun Wang, Zheng Zhou, Shuyang Chen, Jinjun Jiang, Shujing Chen","doi":"10.1155/2024/6622950","DOIUrl":"https://doi.org/10.1155/2024/6622950","url":null,"abstract":"Our research addresses the critical environmental issue of a fine particulate matter (PM2.5), focusing on its association with the increased infection risks. We explored the influence of PM2.5 on human beta-defensin 1 (HBD1), an essential peptide in mucosal immunity found in the airway epithelium. Using C57BL/6J mice and human bronchial epithelial cells (HBE), we examined the effects of PM2.5 exposure followed by <i>Pseudomonas aeruginosa (P. aeruginosa)</i> infection on HBD1 expression at both mRNA and protein levels. The study revealed that PM2.5’s toxicity to epithelial cells and animals varies with time and concentration. Notably, HBE cells exposed to PM2.5 and <i>P. aeruginosa</i> showed increased bacterial invasion and decreased HBD1 expression compared to the cells exposed to <i>P. aeruginosa</i> alone. Similarly, mice studies indicated that combined exposure to PM2.5 and <i>P. aeruginosa</i> significantly reduced survival rates and increased bacterial invasion. These harmful effects, however, were alleviated by administering exogenous HBD1. Furthermore, our findings highlight the activation of MAPK and NF-<i>κ</i>B pathways following PM2.5 exposure. Inhibiting these pathways effectively increased HBD1 expression and diminished bacterial invasion. In summary, our study establishes that PM2.5 exposure intensifies <i>P. aeruginosa</i> invasion in both HBE cells and mouse models, primarily by suppressing HBD1 expression. This effect can be counteracted with exogenous HBD1, with the downregulation mechanism involving the MAPK and NF-<i>κ</i>B pathways. Our study endeavors to elucidate the pathogenesis of lung infections associated with PM2.5 exposure, providing a novel theoretical basis for the development of prevention and treatment strategies, with substantial clinical significance.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139588520","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}
Since the COVID-19 outbreak, the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus has evolved into variants with varied infectivity. Vaccines developed against COVID-19 infection have boosted immunity, but there is still uncertainty on how long the immunity from natural infection or vaccination will last. The present study attempts to outline the present level of information about the contagiousness and spread of SARS-CoV-2 variants of interest and variants of concern (VOCs). The keywords like COVID-19 vaccine types, VOCs, universal vaccines, bivalent, and other relevant terms were searched in NCBI, Science Direct, and WHO databases to review the published literature. The review provides an integrative discussion on the current state of knowledge on the type of vaccines developed against SARS-CoV-2, the safety and efficacy of COVID-19 vaccines concerning the VOCs, and prospects of novel universal, chimeric, and bivalent mRNA vaccines efficacy to fend off existing variants and other emerging coronaviruses. Genomic variation can be quite significant, as seen by the notable differences in impact, transmission rate, morbidity, and death during several human coronavirus outbreaks. Therefore, understanding the amount and characteristics of coronavirus genetic diversity in historical and contemporary strains can help researchers get an edge over upcoming variants.
{"title":"Challenges in Emerging Vaccines and Future Promising Candidates against SARS-CoV-2 Variants","authors":"Tanmay Ghildiyal, Nishant Rai, Janhvi Mishra Rawat, Maargavi Singh, Jigisha Anand, Gaurav Pant, Gaurav Kumar, Amrullah Shidiki","doi":"10.1155/2024/9125398","DOIUrl":"https://doi.org/10.1155/2024/9125398","url":null,"abstract":"Since the COVID-19 outbreak, the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus has evolved into variants with varied infectivity. Vaccines developed against COVID-19 infection have boosted immunity, but there is still uncertainty on how long the immunity from natural infection or vaccination will last. The present study attempts to outline the present level of information about the contagiousness and spread of SARS-CoV-2 variants of interest and variants of concern (VOCs). The keywords like COVID-19 vaccine types, VOCs, universal vaccines, bivalent, and other relevant terms were searched in NCBI, Science Direct, and WHO databases to review the published literature. The review provides an integrative discussion on the current state of knowledge on the type of vaccines developed against SARS-CoV-2, the safety and efficacy of COVID-19 vaccines concerning the VOCs, and prospects of novel universal, chimeric, and bivalent mRNA vaccines efficacy to fend off existing variants and other emerging coronaviruses. Genomic variation can be quite significant, as seen by the notable differences in impact, transmission rate, morbidity, and death during several human coronavirus outbreaks. Therefore, understanding the amount and characteristics of coronavirus genetic diversity in historical and contemporary strains can help researchers get an edge over upcoming variants.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"163 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559933","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}
Objective. Age-related mitochondrial dysfunction and associated oxidative stress may contribute to the development of osteoarthritis. The aim of this study was to identify hub genes associated with mitochondrial dysfunction in osteoarthritis (OA) patients, helping predict the risk of OA, and revealing the mechanism of OA progression. Methods. OA expression data and mitochondrial dysfunction genes were downloaded from GEO (GSE55235, GSE82107, and GSE114007) and GeneCard databases. The differentially expressed mitochondrial dysfunction genes (DEMDFGs) between OA and control samples were screened. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathways were analyzed for DEMDFGs. The hub genes were determined by WGCNA and LASSO regression analysis. ROC curves manifested the diagnostic efficacy of each hub gene. A nomogram model was constructed and validated to predict OA risk. The expression of hub genes in OA and normal chondrocytes was verified by external datasets, qRT-PCR and western blotting. Results. A total of 31 DEMDFGs were identified, with 15 genes upregulated and 16 genes downregulated. GO functional enrichment analysis revealed that DEMDFGs were enriched in biological processes related to energy metabolism and cellular respiration. By employing weighted gene coexpression network analysis, we identified four distinct coexpression modules, among which the blue module exhibited the strongest correlation with OA. The intersection between DEMDFGs and this module yielded eight candidate genes. After LASSO analysis of the data, four hub genes (ACADL, CYBA, SLC19A2, and UCP2) were identified as potential biomarkers for OA. The expression levels of these four genes were externally validated in the GSE114007 dataset. And the biologically differential expression of these four genes has been verified in OA and normal chondrocytes. Moreover, the four hub genes had good sensitivity and specificity by ROC curve analysis, and the risk model constructed with these four genes showed promising performance. In conclusion, our study may provide novel mitochondrial dysfunction hub genes with potential clinical applications for understanding the pathology, diagnosis, and treatment of OA.
目的。与年龄有关的线粒体功能障碍和相关的氧化应激可能会导致骨关节炎的发生。本研究旨在确定骨关节炎（OA）患者中与线粒体功能障碍相关的枢纽基因，帮助预测 OA 的风险，并揭示 OA 进展的机制。研究方法从 GEO（GSE55235、GSE82107 和 GSE114007）和 GeneCard 数据库下载 OA 表达数据和线粒体功能障碍基因。筛选了 OA 样本和对照样本之间的线粒体功能障碍差异表达基因（DEMDFGs）。对 DEMDFGs 的基因本体（GO）和京都基因和基因组通路百科全书进行了分析。通过 WGCNA 和 LASSO 回归分析确定了枢纽基因。ROC 曲线显示了每个枢纽基因的诊断功效。构建并验证了预测 OA 风险的提名图模型。通过外部数据集、qRT-PCR和Western blotting验证了枢纽基因在OA和正常软骨细胞中的表达。结果。共鉴定出31个DEMDFGs，其中15个基因上调，16个基因下调。GO功能富集分析表明，DEMDFGs富集于与能量代谢和细胞呼吸相关的生物过程。通过加权基因共表达网络分析，我们发现了四个不同的共表达模块，其中蓝色模块与OA的相关性最强。DEMDFGs 与该模块的交集产生了八个候选基因。在对数据进行 LASSO 分析后，四个中心基因（ACADL、CYBA、SLC19A2 和 UCP2）被确定为 OA 的潜在生物标志物。这四个基因的表达水平在 GSE114007 数据集中得到了外部验证。这四个基因在 OA 和正常软骨细胞中的生物差异表达也得到了验证。此外，通过 ROC 曲线分析，这四个枢纽基因具有良好的灵敏度和特异性，用这四个基因构建的风险模型表现出良好的性能。总之，我们的研究为了解 OA 的病理、诊断和治疗提供了新的线粒体功能障碍枢纽基因，具有潜在的临床应用价值。
{"title":"Identification and Verification of Hub Mitochondrial Dysfunction Genes in Osteoarthritis Based on Bioinformatics Analysis","authors":"Hui Niu, Xingxing Deng, Qian Zhang, Yijun Zhao, Jinfeng Wen, Wenyu Li, Huan Liu, Xiong Guo, Cuiyan Wu","doi":"10.1155/2024/6822664","DOIUrl":"https://doi.org/10.1155/2024/6822664","url":null,"abstract":"<i>Objective</i>. Age-related mitochondrial dysfunction and associated oxidative stress may contribute to the development of osteoarthritis. The aim of this study was to identify hub genes associated with mitochondrial dysfunction in osteoarthritis (OA) patients, helping predict the risk of OA, and revealing the mechanism of OA progression. <i>Methods</i>. OA expression data and mitochondrial dysfunction genes were downloaded from GEO (GSE55235, GSE82107, and GSE114007) and GeneCard databases. The differentially expressed mitochondrial dysfunction genes (DEMDFGs) between OA and control samples were screened. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathways were analyzed for DEMDFGs. The hub genes were determined by WGCNA and LASSO regression analysis. ROC curves manifested the diagnostic efficacy of each hub gene. A nomogram model was constructed and validated to predict OA risk. The expression of hub genes in OA and normal chondrocytes was verified by external datasets, qRT-PCR and western blotting. <i>Results</i>. A total of 31 DEMDFGs were identified, with 15 genes upregulated and 16 genes downregulated. GO functional enrichment analysis revealed that DEMDFGs were enriched in biological processes related to energy metabolism and cellular respiration. By employing weighted gene coexpression network analysis, we identified four distinct coexpression modules, among which the blue module exhibited the strongest correlation with OA. The intersection between DEMDFGs and this module yielded eight candidate genes. After LASSO analysis of the data, four hub genes (ACADL, CYBA, SLC19A2, and UCP2) were identified as potential biomarkers for OA. The expression levels of these four genes were externally validated in the GSE114007 dataset. And the biologically differential expression of these four genes has been verified in OA and normal chondrocytes. Moreover, the four hub genes had good sensitivity and specificity by ROC curve analysis, and the risk model constructed with these four genes showed promising performance. In conclusion, our study may provide novel mitochondrial dysfunction hub genes with potential clinical applications for understanding the pathology, diagnosis, and treatment of OA.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"25 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559511","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}
Sepsis is a disease caused by multiple microbial infections resulting in multiple organ failure. Schistosoma japonicum secreted cystatin (Sj-Cys) is a strong immunomodulator that stimulates M2 macrophages and alleviates inflammatory damage caused by sepsis. To determine whether the therapeutic effect of Sj-Cys on sepsis can be conveyed by the exosomes released by Sj-Cys-stimulated macrophages, RAW264.7 macrophages were stimulated with rSj-Cys in vitro, the exosomes were obtained from the cell culture supernatant by ultracentrifugation. Sepsis was induced in BALB/c mice by cecal ligation and puncture (CLP). The septic mice were treated with exosomes derived from Sj-Cys-treated macrophages. The treatment effect of exosomes on sepsis was assessed by examining the survival rate of mice up to 72 hr and measuring serum levels of inflammatory cytokines, liver/kidney damage biomarkers, and observing pathological changes in tissue sections. The tissue levels of M1, M2 macrophage surface markers, and TRL2/MyD88 were measured to explore possible mechanisms. Results. Exosomes derived from Sj-Cys-treated macrophages exhibited significant therapeutic effect on CLP-induced sepsis in mice with prolonged survival rate and less damage of critical organs by downregulating the proinflammatory factors TNF-α and IL-6 and upregulating the anti-inflammatory factor TGF-β. The therapeutic effect of exosomes is associated with macrophage polarization from M1 to M2 in the infected tissues via downregulating TRL2/MyD88 inflammatory pathway. Conclusions. Exosomes derived from Sj-Cys-treated macrophages attenuated sepsis in mice through promoting macrophage polarization from M1 to M2 and reducing inflammatory responses, possibly via downregulating TLR2/MyD88 inflammatory signaling pathway. This offers new approaches for immunotherapy of sepsis.
{"title":"Exosomes Derived from Schistosoma japonicum Cystatin-Treated Macrophages Attenuated CLP-Induced Sepsis in Mice","authors":"Feifei Huang, Yayun Qian, Huihui Li, Liang Chu, Chen Wan, Qili Shen, Qianqian Li, Xiuxiu Li, Xinyue Wu, Bin Zhan, Rui Zhou, Xiaodi Yang","doi":"10.1155/2024/8626082","DOIUrl":"https://doi.org/10.1155/2024/8626082","url":null,"abstract":"Sepsis is a disease caused by multiple microbial infections resulting in multiple organ failure. <i>Schistosoma japonicum</i> secreted cystatin (<i>Sj</i>-Cys) is a strong immunomodulator that stimulates M2 macrophages and alleviates inflammatory damage caused by sepsis. To determine whether the therapeutic effect of <i>Sj</i>-Cys on sepsis can be conveyed by the exosomes released by <i>Sj</i>-Cys-stimulated macrophages, RAW264.7 macrophages were stimulated with r<i>Sj</i>-Cys <i>in vitro</i>, the exosomes were obtained from the cell culture supernatant by ultracentrifugation. Sepsis was induced in BALB/c mice by cecal ligation and puncture (CLP). The septic mice were treated with exosomes derived from <i>Sj</i>-Cys-treated macrophages. The treatment effect of exosomes on sepsis was assessed by examining the survival rate of mice up to 72 hr and measuring serum levels of inflammatory cytokines, liver/kidney damage biomarkers, and observing pathological changes in tissue sections. The tissue levels of M1, M2 macrophage surface markers, and TRL2/MyD88 were measured to explore possible mechanisms. <i>Results</i>. Exosomes derived from <i>Sj</i>-Cys-treated macrophages exhibited significant therapeutic effect on CLP-induced sepsis in mice with prolonged survival rate and less damage of critical organs by downregulating the proinflammatory factors TNF-<i>α</i> and IL-6 and upregulating the anti-inflammatory factor TGF-<i>β</i>. The therapeutic effect of exosomes is associated with macrophage polarization from M1 to M2 in the infected tissues via downregulating TRL2/MyD88 inflammatory pathway. <i>Conclusions</i>. Exosomes derived from <i>Sj</i>-Cys-treated macrophages attenuated sepsis in mice through promoting macrophage polarization from M1 to M2 and reducing inflammatory responses, possibly via downregulating TLR2/MyD88 inflammatory signaling pathway. This offers new approaches for immunotherapy of sepsis.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"10 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559890","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}
Rheumatoid arthritis (RA) represents the autoimmune disorder that shows aggressive arthritis as the main symptom. It is difficult to treat and can lead to joint deformation and function loss. At present, Trichinella spiralis (T. spiralis) antigen has attracted much attention because it plays a role in host immune regulatory mechanisms. Therefore, we selected T. spiralis recombinant protein 43 (Tsp43) to treat the bovine collagen type II (BCII)-induced mice RA model and explored its therapeutic mechanisms. This work first verified that Tsp43 could promote the expression of indoleamine 2, 3-dioxygenase (IDO) in dendritic cells (DCs) in vitro. Then, we randomized BALB/c mice (8 weeks old) into six groups, including control, phosphate buffer saline (PBS), BCII, BCII + heat inactivated Tsp43 (HiTsp43), BCII + Tsp43, and BCII + Tsp43 + 1-methyl-troptophan (1-MT) groups. To determine the therapeutic effect of Tsp43 on the BCII-induced mice RA model, relevant cytokines in each group and pathological changes in ankle joints were detected. To explore the mechanisms of Tsp43 on the BCII-induced mice RA model, we checked the expression of IDO in each group, CD4+T cell proliferation, and apoptosis. Collectively, Tsp43 decreased tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) expression in BCII-induced mice RA model and recovered the ankle injury to a certain extent. Tsp43 promoted high expression of IDO, caused expression of related apoptotic proteins in CD4+T cells, and caused apoptosis in CD4+T cells. In addition, Tsp43 reduced the proliferation of CD4+T cells. However, these effects can be inhibited by 1-MT (IDO inhibitor). These results suggested that Tsp43 played an important role in the treatment of arthritis by inhibiting the proliferation of CD4+T cells and inducing CD4+T cells apoptosis through the high expression of IDO. The purpose of this experiment was to provide a new idea for the treatment of RA and lay a foundation for the development of parasite-derived drugs for the treatment of RA.
{"title":"Alleviation of Rheumatoid Arthritis by Inducing IDO Expression with Trichinella spiralis Recombinant Protein 43","authors":"Xiao Ma, Dongming Liu, Wenhao Yu, Caixia Han","doi":"10.1155/2024/8816919","DOIUrl":"https://doi.org/10.1155/2024/8816919","url":null,"abstract":"Rheumatoid arthritis (RA) represents the autoimmune disorder that shows aggressive arthritis as the main symptom. It is difficult to treat and can lead to joint deformation and function loss. At present, <i>Trichinella spiralis</i> (<i>T. spiralis</i>) antigen has attracted much attention because it plays a role in host immune regulatory mechanisms. Therefore, we selected <i>T. spiralis</i> recombinant protein 43 (Tsp43) to treat the bovine collagen type II (BCII)-induced mice RA model and explored its therapeutic mechanisms. This work first verified that Tsp43 could promote the expression of indoleamine 2, 3-dioxygenase (IDO) in dendritic cells (DCs) in vitro. Then, we randomized BALB/c mice (8 weeks old) into six groups, including control, phosphate buffer saline (PBS), BCII, BCII + heat inactivated Tsp43 (HiTsp43), BCII + Tsp43, and BCII + Tsp43 + 1-methyl-troptophan (1-MT) groups. To determine the therapeutic effect of Tsp43 on the BCII-induced mice RA model, relevant cytokines in each group and pathological changes in ankle joints were detected. To explore the mechanisms of Tsp43 on the BCII-induced mice RA model, we checked the expression of IDO in each group, CD4<sup>+</sup>T cell proliferation, and apoptosis. Collectively, Tsp43 decreased tumor necrosis factor-<i>α</i> (TNF-<i>α</i>) and interleukin-1<i>β</i> (IL-1<i>β</i>) expression in BCII-induced mice RA model and recovered the ankle injury to a certain extent. Tsp43 promoted high expression of IDO, caused expression of related apoptotic proteins in CD4<sup>+</sup>T cells, and caused apoptosis in CD4<sup>+</sup>T cells. In addition, Tsp43 reduced the proliferation of CD4<sup>+</sup>T cells. However, these effects can be inhibited by 1-MT (IDO inhibitor). These results suggested that Tsp43 played an important role in the treatment of arthritis by inhibiting the proliferation of CD4<sup>+</sup>T cells and inducing CD4<sup>+</sup>T cells apoptosis through the high expression of IDO. The purpose of this experiment was to provide a new idea for the treatment of RA and lay a foundation for the development of parasite-derived drugs for the treatment of RA.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"29 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139481108","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}
Superantigens are virulence factors secreted by microorganisms that can cause various immune diseases, such as overactivating the immune system, resulting in cytokine storms, rheumatoid arthritis, and multiple sclerosis. Some studies have demonstrated that superantigens do not require intracellular processing and instated bind as intact proteins to the antigen-binding groove of major histocompatibility complex II on antigen-presenting cells, resulting in the activation of T cells with different T-cell receptor Vβ and subsequent overstimulation. To combat superantigen-mediated diseases, researchers have employed different approaches, such as antibodies and simulated peptides. However, due to the complex nature of superantigens, these approaches have not been entirely successful in achieving optimal therapeutic outcomes. CD28 interacts with members of the B7 molecule family to activate T cells. Its mimicking peptide has been suggested as a potential candidate to block superantigens, but it can lead to reduced T-cell activity while increasing the host’s infection risk. Thus, this review focuses on the use of drug delivery methods to accurately target and block superantigens, while reducing the adverse effects associated with CD28 mimic peptides. We believe that this method has the potential to provide an effective and safe therapeutic strategy for superantigen-mediated diseases.
超级抗原是微生物分泌的毒力因子，可引起各种免疫疾病，如过度激活免疫系统，导致细胞因子风暴、类风湿性关节炎和多发性硬化症。一些研究表明，超级抗原不需要在细胞内加工，而是以完整蛋白质的形式与抗原递呈细胞上主要组织相容性复合体 II 的抗原结合槽结合，从而激活具有不同 T 细胞受体 Vβ 的 T 细胞，继而导致过度刺激。为了应对超抗原介导的疾病，研究人员采用了不同的方法，如抗体和模拟肽。然而，由于超抗原的复杂性，这些方法并不能完全达到最佳治疗效果。CD28 与 B7 分子家族成员相互作用，激活 T 细胞。它的模拟肽被认为是阻断超级抗原的潜在候选物，但它会导致 T 细胞活性降低，同时增加宿主的感染风险。因此，本综述将重点讨论如何利用给药方法准确靶向和阻断超级抗原，同时减少 CD28 拟态肽带来的不良反应。我们相信，这种方法有可能为超抗原介导的疾病提供一种有效而安全的治疗策略。
{"title":"Blocking Superantigen-Mediated Diseases: Challenges and Future Trends","authors":"Pengbo Wang, Zina Fredj, Hongyong Zhang, Guoguang Rong, Sumin Bian, Mohamad Sawan","doi":"10.1155/2024/2313062","DOIUrl":"https://doi.org/10.1155/2024/2313062","url":null,"abstract":"Superantigens are virulence factors secreted by microorganisms that can cause various immune diseases, such as overactivating the immune system, resulting in cytokine storms, rheumatoid arthritis, and multiple sclerosis. Some studies have demonstrated that superantigens do not require intracellular processing and instated bind as intact proteins to the antigen-binding groove of major histocompatibility complex II on antigen-presenting cells, resulting in the activation of T cells with different T-cell receptor V<i>β</i> and subsequent overstimulation. To combat superantigen-mediated diseases, researchers have employed different approaches, such as antibodies and simulated peptides. However, due to the complex nature of superantigens, these approaches have not been entirely successful in achieving optimal therapeutic outcomes. CD28 interacts with members of the B7 molecule family to activate T cells. Its mimicking peptide has been suggested as a potential candidate to block superantigens, but it can lead to reduced T-cell activity while increasing the host’s infection risk. Thus, this review focuses on the use of drug delivery methods to accurately target and block superantigens, while reducing the adverse effects associated with CD28 mimic peptides. We believe that this method has the potential to provide an effective and safe therapeutic strategy for superantigen-mediated diseases.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"24 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139481102","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}
Xueshan Huang, Min Yang, Ma Ye, Jun Qiu, Yanping Chen
<i>Objective</i>. To explore the impact of non-pharmacological interventions on inhaled allergen sensitization in children during the COVID-19 pandemic. <i>Methods</i>. The positive rate of inhaled allergens, allergens sIgE grade, and multiple sensitization rates before and during the pandemic were analyzed retrospectively in this study. Logistic regression analysis was used to compare the positive rate of allergens before and during the pandemic, using odds ratio (OR) and OR 95% CI to investigate the impact of the pandemic on allergen sensitization. <i>Results</i>. Positive rates of d1 (49.5% vs. 38.5%), d2 (50.2% vs. 32.2%), e2 (10.1% vs. 6.1%), e1 (6.2% vs. 1.7%), mx2 (10.1% vs. 2.7%), sycamore (7.2% vs. 2.1%), w1 (4.0% vs. 1.7%), elm (3.1% vs. 0.6%), w6 (3.0% vs. 1.7%), and u80 (1.3% vs. 0.5%) increased significantly during the COVID-19 pandemic. After adjusting gender, age, season, and other potential influencing factors, the COVID-19 pandemic was found to be a risk factor for the positive rate of d1 (OR = 1.174, 95% CI = 1.015–1.358), d2 (OR = 1.301, 95% CI = 1.093–1.549), e2 (OR = 1.499, 95% CI = 1.280–1.756), mx2 (OR = 3.959, 95% CI = 3.358–4.446), w1 (OR = 1.828, 95% CI = 1.353–2.470, w6 (OR = 1.538, 95% CI = 1.123–2.106)), and u80 (OR = 2.521, 95% CI = 1.413–4.497) (<i><span><svg height="9.2729pt" style="vertical-align:-0.6370001pt" version="1.1" viewbox="-0.0498162 -8.6359 19.289 9.2729" width="19.289pt" 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,-0.013,11.658,0)"></path></g></svg><span></span><svg height="9.2729pt" style="vertical-align:-0.6370001pt" version="1.1" viewbox="22.8711838 -8.6359 21.918 9.2729" width="21.918pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,22.921,0)"></path></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"></path></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"></path></g></svg></span></i>). In addition, d1 and d2 allergen sIgE grades increased during the COVID-19 pandemic (d1: <i>χ</i><sup>2</sup> = 9.576, <span><svg height="9.2729pt" style="vertical-align:-0.6370001pt" version="1.1" viewbox="-0.0498162 -8.6359 19.289 9.2729" width="19.289pt" 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)"><use xlink:href="#g113-81"></use></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-91"></use></g></svg><span></span><span><svg height="9.2729pt" style="vertical-align:-0.6370001pt" version="1.1" viewbox="22.8711838 -8.6359 21.918 9.2729" width="21.918pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,
目的探讨在 COVID-19 大流行期间，非药物干预对儿童吸入过敏原致敏的影响。方法。本研究对大流行之前和期间的吸入性过敏原阳性率、过敏原 sIgE 等级和多重致敏率进行了回顾性分析。采用 Logistic 回归分析比较大流行前和大流行期间的过敏原阳性率，并使用比值比（OR）和比值比 95% CI 研究大流行对过敏原致敏的影响。结果显示d1 (49.5% vs. 38.5%)、d2 (50.2% vs. 32.2%)、e2 (10.1% vs. 6.1%)、e1 (6.2% vs. 1.7%)、mx2 (10.1% vs. 2.7%)、梧桐 (7.2% vs. 2.1%)2.1%）、w1（4.0% vs. 1.7%）、榆树（3.1% vs. 0.6%）、w6（3.0% vs. 1.7%）和 u80（1.3% vs. 0.5%）在 COVID-19 大流行期间显著增加。在对性别、年龄、季节和其他潜在影响因素进行调整后，发现 COVID-19 大流行是 d1（OR = 1.174，95% CI = 1.015-1.358）、d2（OR = 1.301，95% CI = 1.093-1.549）、e2（OR = 1.301，95% CI = 1.093-1.549549）、e2（OR = 1.499，95% CI = 1.280-1.756）、mx2（OR = 3.959，95% CI = 3.358-4.446）、w1（OR = 1.828，95% CI = 1.353-2.470）、w6（OR = 1.538，95% CI = 1.123-2.106））和 u80（OR = 2.521，95% CI = 1.413-4.497）（）。此外，在 COVID-19 大流行期间，d1 和 d2 过敏原 sIgE 等级有所上升（d1：χ2 = 9.576，；d2：χ2 = 39.063，）。多重过敏的比例明显高于大流行前，具有统计学意义（χ2 = 1621.815，）。结论在 COVID-19 大流行期间，非药物干预增加了儿童对室内和室外过敏原的阳性率。尘螨过敏原的 sIgE 等级和多重致敏率明显高于 COVID-19 之前。
{"title":"Impact of the COVID-19 Epidemic on Inhalant Allergen Sensitization in Children","authors":"Xueshan Huang, Min Yang, Ma Ye, Jun Qiu, Yanping Chen","doi":"10.1155/2024/5641948","DOIUrl":"https://doi.org/10.1155/2024/5641948","url":null,"abstract":"<i>Objective</i>. To explore the impact of non-pharmacological interventions on inhaled allergen sensitization in children during the COVID-19 pandemic. <i>Methods</i>. The positive rate of inhaled allergens, allergens sIgE grade, and multiple sensitization rates before and during the pandemic were analyzed retrospectively in this study. Logistic regression analysis was used to compare the positive rate of allergens before and during the pandemic, using odds ratio (OR) and OR 95% CI to investigate the impact of the pandemic on allergen sensitization. <i>Results</i>. Positive rates of d1 (49.5% vs. 38.5%), d2 (50.2% vs. 32.2%), e2 (10.1% vs. 6.1%), e1 (6.2% vs. 1.7%), mx2 (10.1% vs. 2.7%), sycamore (7.2% vs. 2.1%), w1 (4.0% vs. 1.7%), elm (3.1% vs. 0.6%), w6 (3.0% vs. 1.7%), and u80 (1.3% vs. 0.5%) increased significantly during the COVID-19 pandemic. After adjusting gender, age, season, and other potential influencing factors, the COVID-19 pandemic was found to be a risk factor for the positive rate of d1 (OR = 1.174, 95% CI = 1.015–1.358), d2 (OR = 1.301, 95% CI = 1.093–1.549), e2 (OR = 1.499, 95% CI = 1.280–1.756), mx2 (OR = 3.959, 95% CI = 3.358–4.446), w1 (OR = 1.828, 95% CI = 1.353–2.470, w6 (OR = 1.538, 95% CI = 1.123–2.106)), and u80 (OR = 2.521, 95% CI = 1.413–4.497) (<i><span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 9.2729\" width=\"19.289pt\" 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,-0.013,11.658,0)\"></path></g></svg><span></span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 21.918 9.2729\" width=\"21.918pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,32.125,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.365,0)\"></path></g></svg></span></i>). In addition, d1 and d2 allergen sIgE grades increased during the COVID-19 pandemic (d1: <i>χ</i><sup>2</sup> = 9.576, <span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 9.2729\" width=\"19.289pt\" 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)\"><use xlink:href=\"#g113-81\"></use></g><g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"><use xlink:href=\"#g117-91\"></use></g></svg><span></span><span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 21.918 9.2729\" width=\"21.918pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"113 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139475467","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}
Toll-like receptors (TLRs) belong to a germline-encoded protein family. These are pattern recognition receptors. They sense pathogen-associated molecular patterns (PAMPs). When this occurs, activation of the NF-ĸB pathway follows. This triggers the innate immune response of the host. The consequent inflammatory cytokine response usually contributes to the elimination of the pathogen. Activation of TLRs also induces an adaptive immune response by a cross-prime mechanism. This mechanism is employed in cancer immunotherapy. Using TLR ligands as adjuvants induces upregulation of costimulatory signals which in turn activates a cytotoxic leukocyte response against cancer cells. However, TLRs are also overexpressed in human cancer cells resulting in increased cell proliferation, migration, invasion, and angiogenesis. An intracellular adaptor, myeloid differentiation factor 88 (MyD88) probably mediates this process. MyD88 is intimately involved with all TLRs except TLR3. One consequence of the interaction between a TLR and MyD88 is activation of NF-ĸB. In this context of a variety of proinflammtory cytokines being produced, chronic inflammation may result. Inflammation is an important protective mechanism. However, chronic inflammation is also involved in carcinogenesis. Activation of NF-ĸB inhibits apoptosis and under certain circumstances, tumor cell survival. In this review, the potential therapeutic value of TLRs in immunotherapy and its role in oncogenesis are explored. The emerging use of artificial intelligence is mentioned.
{"title":"Multiple Factors Determine the Oncolytic or Carcinogenic Effects of TLRs Activation in Cancer","authors":"Yingxiang Yang, Chengyue Jin, Anthony Yeo, Bo Jin","doi":"10.1155/2024/1111551","DOIUrl":"https://doi.org/10.1155/2024/1111551","url":null,"abstract":"Toll-like receptors (TLRs) belong to a germline-encoded protein family. These are pattern recognition receptors. They sense pathogen-associated molecular patterns (PAMPs). When this occurs, activation of the NF-<i>ĸ</i>B pathway follows. This triggers the innate immune response of the host. The consequent inflammatory cytokine response usually contributes to the elimination of the pathogen. Activation of TLRs also induces an adaptive immune response by a cross-prime mechanism. This mechanism is employed in cancer immunotherapy. Using TLR ligands as adjuvants induces upregulation of costimulatory signals which in turn activates a cytotoxic leukocyte response against cancer cells. However, TLRs are also overexpressed in human cancer cells resulting in increased cell proliferation, migration, invasion, and angiogenesis. An intracellular adaptor, myeloid differentiation factor 88 (MyD88) probably mediates this process. MyD88 is intimately involved with all TLRs except TLR3. One consequence of the interaction between a TLR and MyD88 is activation of NF-<i>ĸ</i>B. In this context of a variety of proinflammtory cytokines being produced, chronic inflammation may result. Inflammation is an important protective mechanism. However, chronic inflammation is also involved in carcinogenesis. Activation of NF-<i>ĸ</i>B inhibits apoptosis and under certain circumstances, tumor cell survival. In this review, the potential therapeutic value of TLRs in immunotherapy and its role in oncogenesis are explored. The emerging use of artificial intelligence is mentioned.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"82 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139464617","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}
The density of CD169+ macrophages has been reported to positively correlate with the number of CD8+ T cells, although this remains controversial. To better understand this topic, we conducted a meta-analysis. We searched the PubMed, Medline, and Web of Science databases for studies that were published before May 2022 and performed a meta-analysis of the incidence of low and high CD169 expression in groups based on CD8 expression using the random-effects model. A total of 10 studies were included in the meta-analysis. The incidence of high CD169 expression in lymph nodes was significantly lower than that of low CD169 expression in the low CD8 expression group (odds ratio (OR): 0.76, 95% confidence interval (CI): 0.6, 0.96); however, the incidence of high CD169 expression in lymph nodes was higher than that of low CD169 expression in the high CD8 expression group (OR: 1.50, 95% CI: 1.08, 2.07). We also found that the expression of CD169 in tumors was lower than that in nontumor tissues (standardized mean difference: −5.29, 95% CI: −7.47, −3.11). The overall survival and hazard ratio of patients with high and low CD169 expression was 0.45 (95% CI: 0.37, 0.55). This analysis showed that high CD169 expression was associated with a high CD8 expression, and low CD169 expression was associated with low CD8 expression. The risk of death was 55% lower for patients with high CD169 expression, and high CD169 expression may be associated with favorable survival outcomes in cancer patients. However, the number and heterogeneity of the studies should be taken into consideration when evaluating the analysis. High-quality randomized controlled trials on the association between CD169 and CD8 expression are needed to verify these effects.
{"title":"CD169 Expression in Lymph Nodes is Associated with Increased Infiltration of CD8+ T Cells in Tumors: A Systematic Review and Meta-Analysis","authors":"Yong Wang, Xiao-Ting Wu, Jing Chen","doi":"10.1155/2024/8873767","DOIUrl":"https://doi.org/10.1155/2024/8873767","url":null,"abstract":"The density of CD169<sup>+</sup> macrophages has been reported to positively correlate with the number of CD8<sup>+</sup> T cells, although this remains controversial. To better understand this topic, we conducted a meta-analysis. We searched the PubMed, Medline, and Web of Science databases for studies that were published before May 2022 and performed a meta-analysis of the incidence of low and high CD169 expression in groups based on CD8 expression using the random-effects model. A total of 10 studies were included in the meta-analysis. The incidence of high CD169 expression in lymph nodes was significantly lower than that of low CD169 expression in the low CD8 expression group (odds ratio (OR): 0.76, 95% confidence interval (CI): 0.6, 0.96); however, the incidence of high CD169 expression in lymph nodes was higher than that of low CD169 expression in the high CD8 expression group (OR: 1.50, 95% CI: 1.08, 2.07). We also found that the expression of CD169 in tumors was lower than that in nontumor tissues (standardized mean difference: −5.29, 95% CI: −7.47, −3.11). The overall survival and hazard ratio of patients with high and low CD169 expression was 0.45 (95% CI: 0.37, 0.55). This analysis showed that high CD169 expression was associated with a high CD8 expression, and low CD169 expression was associated with low CD8 expression. The risk of death was 55% lower for patients with high CD169 expression, and high CD169 expression may be associated with favorable survival outcomes in cancer patients. However, the number and heterogeneity of the studies should be taken into consideration when evaluating the analysis. High-quality randomized controlled trials on the association between CD169 and CD8 expression are needed to verify these effects.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"5 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139464649","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}
Sujan Kumar Sarkar, Annie M. L. Willson, Margaret A. Jordan
Multiple sclerosis (MS) is a neurodegenerative autoimmune disease characterized by the destruction of the myelin sheath of the neuronal axon in the central nervous system. Many risk factors, including environmental, epigenetic, genetic, and lifestyle factors, are responsible for the development of MS. It has long been thought that only adaptive immune cells, especially autoreactive T cells, are responsible for the pathophysiology; however, recent evidence has indicated that innate immune cells are also highly involved in disease initiation and progression. Here, we compile the available data regarding the role immune cells play in MS, drawn from both human and animal research. While T and B lymphocytes, chiefly enhance MS pathology, regulatory T cells (Tregs) may serve a more protective role, as can B cells, depending on context and location. Cells chiefly involved in innate immunity, including macrophages, microglia, astrocytes, dendritic cells, natural killer (NK) cells, eosinophils, and mast cells, play varied roles. In addition, there is evidence regarding the involvement of innate-like immune cells, such as γδ T cells, NKT cells, MAIT cells, and innate-like B cells as crucial contributors to MS pathophysiology. It is unclear which of these cell subsets are involved in the onset or progression of disease or in protective mechanisms due to their plastic nature, which can change their properties and functions depending on microenvironmental exposure and the response of neural networks in damage control. This highlights the need for a multipronged approach, combining stringently designed clinical data with carefully controlled in vitro and in vivo research findings, to identify the underlying mechanisms so that more effective therapeutics can be developed.
多发性硬化症（MS）是一种神经退行性自身免疫性疾病，其特征是中枢神经系统神经元轴突的髓鞘遭到破坏。多发性硬化症的发病有许多风险因素，包括环境因素、表观遗传因素、基因因素和生活方式因素。长期以来，人们一直认为只有适应性免疫细胞，尤其是自反应性 T 细胞，才是多发性硬化症病理生理学的罪魁祸首；然而，最近的证据表明，先天性免疫细胞也在很大程度上参与了疾病的发生和发展。在此，我们汇编了人类和动物研究中有关免疫细胞在多发性硬化症中作用的现有数据。T淋巴细胞和B淋巴细胞主要增强多发性硬化症的病理变化，而调节性T细胞（Tregs）和B细胞（视具体情况和部位而定）则可能发挥更大的保护作用。主要参与先天性免疫的细胞，包括巨噬细胞、小胶质细胞、星形胶质细胞、树突状细胞、自然杀伤（NK）细胞、嗜酸性粒细胞和肥大细胞，发挥着不同的作用。此外，有证据表明，先天性类免疫细胞，如γδ T 细胞、NKT 细胞、MAIT 细胞和先天性类 B 细胞参与了 MS 病理生理学的关键作用。目前还不清楚这些细胞亚群中哪些参与了疾病的发生、发展或保护机制，因为它们具有可塑性，可根据微环境暴露和神经网络在损伤控制中的反应改变其特性和功能。这凸显了多管齐下的必要性，将严格设计的临床数据与精心控制的体外和体内研究结果相结合，以确定潜在的机制，从而开发出更有效的疗法。
{"title":"The Plasticity of Immune Cell Response Complicates Dissecting the Underlying Pathology of Multiple Sclerosis","authors":"Sujan Kumar Sarkar, Annie M. L. Willson, Margaret A. Jordan","doi":"10.1155/2024/5383099","DOIUrl":"https://doi.org/10.1155/2024/5383099","url":null,"abstract":"Multiple sclerosis (MS) is a neurodegenerative autoimmune disease characterized by the destruction of the myelin sheath of the neuronal axon in the central nervous system. Many risk factors, including environmental, epigenetic, genetic, and lifestyle factors, are responsible for the development of MS. It has long been thought that only adaptive immune cells, especially autoreactive T cells, are responsible for the pathophysiology; however, recent evidence has indicated that innate immune cells are also highly involved in disease initiation and progression. Here, we compile the available data regarding the role immune cells play in MS, drawn from both human and animal research. While T and B lymphocytes, chiefly enhance MS pathology, regulatory T cells (Tregs) may serve a more protective role, as can B cells, depending on context and location. Cells chiefly involved in innate immunity, including macrophages, microglia, astrocytes, dendritic cells, natural killer (NK) cells, eosinophils, and mast cells, play varied roles. In addition, there is evidence regarding the involvement of innate-like immune cells, such as <i>γδ</i> T cells, NKT cells, MAIT cells, and innate-like B cells as crucial contributors to MS pathophysiology. It is unclear which of these cell subsets are involved in the onset or progression of disease or in protective mechanisms due to their plastic nature, which can change their properties and functions depending on microenvironmental exposure and the response of neural networks in damage control. This highlights the need for a multipronged approach, combining stringently designed clinical data with carefully controlled in vitro and in vivo research findings, to identify the underlying mechanisms so that more effective therapeutics can be developed.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"1 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139093541","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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