Journal of Immunology Research最新文献

{"title":"Upper Airway Epithelial Tissue Transcriptome Analysis Reveals Immune Signatures Associated with COVID-19 Severity in Ghanaians","authors":"John Demby Sandi, Joshua I. Levy, Kesego Tapela, Mark Zeller, Joshua Afari Yeboah, Daniel Frimpong Saka, Donald S. Grant, Gordon A. Awandare, Peter K. Quashie, Kristian G. Andersen, Lily Paemka","doi":"10.1155/2024/6668017","DOIUrl":"https://doi.org/10.1155/2024/6668017","url":null,"abstract":"The immunological signatures driving the severity of coronavirus disease 19 (COVID-19) in Ghanaians remain poorly understood. We performed bulk transcriptome sequencing of nasopharyngeal samples from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected Ghanaians with mild and severe COVID-19, as well as healthy controls to characterize immune signatures at the primary SARS-CoV-2 infection site and identify drivers of disease severity. Generally, a heightened antiviral response was observed in SARS-CoV-2-infected Ghanaians compared with uninfected controls. COVID-19 severity was associated with immune suppression, overexpression of proinflammatory cytokines, including <i>CRNN</i>, <i>IL1A</i>, <i>S100A7</i>, and <i>IL23A</i>, and activation of pathways involved in keratinocyte proliferation. <i>SAMD9L</i> was among the differentially regulated interferon-stimulated genes in our mild and severe disease cohorts, suggesting that it may play a critical role in SARS-CoV-2 pathogenesis. By comparing our data with a publicly available dataset from a non-African (Indians) (GSE166530), an elevated expression of antiviral response-related genes was noted in COVID-19-infected Ghanaians. Overall, the study describes immune signatures driving COVID-19 severity in Ghanaians and identifies immune drivers that could serve as potential prognostic markers for future outbreaks or pandemics. It further provides important preliminary evidence suggesting differences in antiviral response at the upper respiratory interface in sub-Saharan Africans (Ghanaians) and non-Africans, which could be contributing to the differences in disease outcomes. Further studies using larger datasets from different populations will expand on these findings.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"41 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139765752","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}

{"title":"RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages","authors":"María José Romero de Ávila, Susana López-López, Aarón García-Blázquez, Almudena Ruiz-García, María Julia González-Gómez, María Luisa Nueda, Victoriano Baladrón, Ignacio Pérez-Roger, Enric Poch, Begoña Ballester-Lurbe, José Javier García-Ramírez, Eva M. Monsalve, María José M. Díaz-Guerra","doi":"10.1155/2024/2264799","DOIUrl":"https://doi.org/10.1155/2024/2264799","url":null,"abstract":"Macrophage activation is a complex process with multiple control elements that ensures an adequate response to the aggressor pathogens and, on the other hand, avoids an excess of inflammatory activity that could cause tissue damage. In this study, we have identified RND3, a small GTP-binding protein, as a new element in the complex signaling process that leads to macrophage activation. We show that RND3 expression is transiently induced in macrophages activated through Toll receptors and potentiated by IFN-<i>γ</i>. We also demonstrate that RND3 increases NOTCH signaling in macrophages by favoring NOTCH1 expression and its nuclear activity; however, Rnd3 expression seems to be inhibited by NOTCH signaling, setting up a negative regulatory feedback loop. Moreover, increased RND3 protein levels seem to potentiate NF<i>κ</i>B and STAT1 transcriptional activity resulting in increased expression of proinflammatory genes, such as <i>Tnf</i>-<i>α</i>, <i>Irf-1</i>, or <i>Cxcl-10</i>. Altogether, our results indicate that RND3 seems to be a new regulatory element which could control the activation of macrophages, able to fine tune the inflammatory response through NOTCH.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"11 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139662023","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}

{"title":"Interleukin-18 Gene Polymorphisms and Rheumatoid Arthritis Susceptibility: An Umbrella Review of Meta-Analyses","authors":"Yuehong Chen, Yali Ye, Huan Liu, Zhongling Luo, Qianwei Li, Qibing Xie","doi":"10.1155/2024/6631033","DOIUrl":"https://doi.org/10.1155/2024/6631033","url":null,"abstract":"This study systematically analyzes the association between interleukin-18 (IL-18) gene polymorphisms and rheumatoid arthritis (RA) susceptibility. The electronic databases Ovid MEDLINE, Ovid Excerpta Medica Database, and Cochrane Library were searched to identify meta-analyses that included case–control studies reporting IL-18 gene polymorphisms and RA susceptibility. Data were reanalyzed using Review Manager Software 5.1, and Mantel–Haenszel random effects were applied for the five genetic models: allelic, recessive, dominant, homozygote, and heterozygote. The effect size of odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated. A total of seven meta-analyses with poor quality were included. The IL-18 polymorphisms -607 A/C, -137 C/G, -920 T/C, and -105 C/A have been reported. With weak evidence, IL-18 -607 A/C polymorphisms were associated with a reduced risk of RA susceptibility using the allele model (OR = 0.76, 95% CI: 0.61 − 0.93, &lt;span&gt;&lt;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\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;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\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;),&lt;/span&gt;&lt;/span&gt; dominant model (OR = 0.67, 95% CI: 0.50 − 0.90, &lt;span&gt;&lt;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\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;use xlink:href=\"#g113-113\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"&gt;&lt;use xlink:href=\"#g117-34\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 28.184 11.7782\" width=\"28.184pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"&gt;&lt;use xlink:href=\"#g113-47\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,44.289,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;),&lt;/span&gt;&lt;/span&gt; homozygote model (OR = 0.57, 95% CI: 0.35 − 0.91, &lt;span&gt;","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"32 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139646294","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}

{"title":"Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell Carcinoma","authors":"Haideh Namdari, Farhad Rezaei, Fatemeh Heidarnejad, Mohammad Yaghoubzad-Maleki, Maryam Karamigolbaghi","doi":"10.1155/2024/2875635","DOIUrl":"https://doi.org/10.1155/2024/2875635","url":null,"abstract":"Renal cell carcinoma (RCC) accounts for the majority of cancer-related deaths worldwide. Overexpression of CD70 has been linked to advanced stages of RCC. Therefore, this study aims to develop a multiepitope vaccine targeting the overexpressed CD70 using immunoinformatics techniques. In this investigation, in silico multiepitope vaccines were constructed by linking specific CD70 protein epitopes for helper T lymphocytes and CD8⁺ T lymphocytes. To enhance immunogenicity, sequences of cell-penetrating peptide (CPP), penetratin (pAntp), along with the entire sequence of tumor necrosis factor-<i>α</i> (TNF-<i>α</i>), were attached to the N-terminal and C-terminal of the CD70 epitopes. Computational assessments were performed on these chimeric vaccines for antigenicity, allergenicity, peptide toxicity, population coverage, and physicochemical properties. Furthermore, refined 3D constructs were subjected to a range of analyses, encompassing structural B-cell epitope prediction and molecular docking. The chosen vaccine construct underwent diverse assessments such as molecular dynamics simulation, immune response simulation, and in silico cloning. All vaccines comprised antigenic, nontoxic, and nonallergenic epitopes, ensuring extensive global population coverage. The vaccine constructs demonstrated favorable physicochemical characteristics. The binding affinity of chimeric vaccines to the TNF receptor remained relatively stable, influenced by the alignment of vaccine components. Molecular docking and dynamics analyses predicted stable interactions between CD70-CPP-TNF and the TNF receptor, indicating potential efficacy. In silico codon optimization and cloning of the vaccine nucleic acid sequence were accomplished using the pET28a plasmid. Furthermore, this vaccine displayed the capacity to modulate humoral and cellular immune responses. Overall, the results suggest therapeutic potential for the chimeric CD70-CPP-TNF vaccine against RCC. However, validation through <i>in vitro</i> and <i>in vivo</i> experiments is necessary. This trial is registered with NCT04696731 and NCT04046445.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"25 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139588480","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}

{"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}

{"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}

{"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}

{"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}

{"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⁺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⁺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.","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}

{"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}