Rodrigo T. Camacho-Pacheco, Jessica Hernández-Pineda, Yesenia Brito-Pérez, Noemi Plazola-Camacho, Irma A. Coronado-Zarco, Gabriela Arreola-Ramírez, Mextli Y. Bermejo-Haro, M. Angel Najera-Hernández, Gabriela González-Pérez, Alma Herrera-Salazar, Andrea Olmos-Ortiz, Diana Soriano-Becerril, Claudia Sandoval-Montes, Ricardo Figueroa-Damian, Sandra Rodríguez-Martínez, Ismael Mancilla-Herrera
Over the last 20 years, the incidence of vertical HIV transmission has decreased from 25%–42% to less than 1%. Although there are no signs of infection, the health of HIV-exposed uninfected (HEU) infants is notoriously affected during the first months of life, with opportunistic infections being the most common disease. Some studies have reported effects on the vertical transfer of antibodies, but little is known about the subclass distribution of these antibodies. We proposed to evaluate the total IgG concentration and its subclasses in HIV+ mothers and HEU pairs and to determine which maternal factors condition their levels. In this study, plasma from 69 HEU newborns, their mothers, and 71 control pairs was quantified via immunoassays for each IgG isotype. Furthermore, we followed the antibody profile of HEUs throughout the first year of life. We showed that mothers present an antibody profile characterized by high concentrations of IgG1 and IgG3 but reduced IgG2, and HEU infants are born with an IgG subclass profile similar to that of their maternal pair. Interestingly, this passively transferred profile could remain influenced even during their own antibody production in HEU infants, depending on maternal conditions such as CD4+ T-cell counts and maternal antiretroviral treatment. Our findings indicate that HEU infants exhibit an altered IgG subclass profile influenced by maternal factors, potentially contributing to their increased susceptibility to infections.
{"title":"Disturbances in the IgG Antibody Profile in HIV-Exposed Uninfected Infants Associated with Maternal Factors","authors":"Rodrigo T. Camacho-Pacheco, Jessica Hernández-Pineda, Yesenia Brito-Pérez, Noemi Plazola-Camacho, Irma A. Coronado-Zarco, Gabriela Arreola-Ramírez, Mextli Y. Bermejo-Haro, M. Angel Najera-Hernández, Gabriela González-Pérez, Alma Herrera-Salazar, Andrea Olmos-Ortiz, Diana Soriano-Becerril, Claudia Sandoval-Montes, Ricardo Figueroa-Damian, Sandra Rodríguez-Martínez, Ismael Mancilla-Herrera","doi":"10.1155/2024/8815767","DOIUrl":"https://doi.org/10.1155/2024/8815767","url":null,"abstract":"Over the last 20 years, the incidence of vertical HIV transmission has decreased from 25%–42% to less than 1%. Although there are no signs of infection, the health of HIV-exposed uninfected (HEU) infants is notoriously affected during the first months of life, with opportunistic infections being the most common disease. Some studies have reported effects on the vertical transfer of antibodies, but little is known about the subclass distribution of these antibodies. We proposed to evaluate the total IgG concentration and its subclasses in HIV+ mothers and HEU pairs and to determine which maternal factors condition their levels. In this study, plasma from 69 HEU newborns, their mothers, and 71 control pairs was quantified via immunoassays for each IgG isotype. Furthermore, we followed the antibody profile of HEUs throughout the first year of life. We showed that mothers present an antibody profile characterized by high concentrations of IgG1 and IgG3 but reduced IgG2, and HEU infants are born with an IgG subclass profile similar to that of their maternal pair. Interestingly, this passively transferred profile could remain influenced even during their own antibody production in HEU infants, depending on maternal conditions such as CD4+ T-cell counts and maternal antiretroviral treatment. Our findings indicate that HEU infants exhibit an altered IgG subclass profile influenced by maternal factors, potentially contributing to their increased susceptibility to infections.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"5 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139765680","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}
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
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 CRNN, IL1A, S100A7, and IL23A, and activation of pathways involved in keratinocyte proliferation. SAMD9L 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.
{"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}
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
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-γ. 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 NFκB and STAT1 transcriptional activity resulting in increased expression of proinflammatory genes, such as Tnf-α, Irf-1, or Cxcl-10. 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.
{"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}
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, <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> dominant model (OR = 0.67, 95% CI: 0.50 − 0.90, <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)"><use xlink:href="#g113-113"></use></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"></use></g></svg><span></span><span><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"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"></use></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)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"></path></g></svg>),</span></span> homozygote model (OR = 0.57, 95% CI: 0.35 − 0.91, <span>
{"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, <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> dominant model (OR = 0.67, 95% CI: 0.50 − 0.90, <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)\"><use xlink:href=\"#g113-113\"></use></g><g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"><use xlink:href=\"#g117-34\"></use></g></svg><span></span><span><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\"><g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"><use xlink:href=\"#g113-47\"></use></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)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,44.289,0)\"></path></g></svg>),</span></span> homozygote model (OR = 0.57, 95% CI: 0.35 − 0.91, <span>","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}
Haideh Namdari, Farhad Rezaei, Fatemeh Heidarnejad, Mohammad Yaghoubzad-Maleki, Maryam Karamigolbaghi
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-α (TNF-α), 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 in vitro and in vivo experiments is necessary. This trial is registered with NCT04696731 and NCT04046445.
肾细胞癌（RCC）占全球癌症相关死亡的大多数。CD70 的过表达与 RCC 晚期有关。因此，本研究旨在利用免疫信息学技术开发一种靶向过表达 CD70 的多位面疫苗。在这项研究中，通过连接辅助 T 淋巴细胞和 CD8+ T 淋巴细胞的特异性 CD70 蛋白表位，构建了硅学多表位疫苗。为了增强免疫原性，在 CD70 表位的 N 端和 C 端连接了细胞穿透肽（CPP）、穿透素（pAntp）序列以及肿瘤坏死因子-α（TNF-α）的整个序列。对这些嵌合疫苗的抗原性、过敏性、肽毒性、群体覆盖率和理化性质进行了计算评估。此外，还对完善的三维结构进行了一系列分析，包括 B 细胞表位结构预测和分子对接。选定的疫苗构建体还接受了分子动力学模拟、免疫反应模拟和硅克隆等多种评估。所有疫苗都包含抗原性、无毒性和非过敏性表位，确保广泛覆盖全球人群。疫苗构建体具有良好的理化特性。受疫苗成分排列的影响，嵌合疫苗与 TNF 受体的结合亲和力保持相对稳定。分子对接和动力学分析预测，CD70-CPP-TNF 与 TNF 受体之间存在稳定的相互作用，显示了潜在的功效。利用 pET28a 质粒完成了疫苗核酸序列的硅学密码子优化和克隆。此外，该疫苗还显示出调节体液和细胞免疫反应的能力。总之，研究结果表明嵌合 CD70-CPP-TNF 疫苗具有治疗 RCC 的潜力。不过，还需要通过体外和体内实验进行验证。该试验已在 NCT04696731 和 NCT04046445 上注册。
{"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<sup>+</sup> 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}
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}
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}
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}
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}
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