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":null,"pages":null},"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":null,"pages":null},"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
Objective. To explore the impact of non-pharmacological interventions on inhaled allergen sensitization in children during the COVID-19 pandemic. Methods. 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. Results. 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) (). In addition, d1 and d2 allergen sIgE grades increased during the COVID-19 pandemic (d1: χ2 = 9.576,
{"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}
Sofia Smargianaki, Evelina Elmér, Sandra Lilliebladh, Sophie Ohlsson, Åsa Pettersson, Thomas Hellmark, Åsa CM Johansson
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases with inflammation affecting small blood vessels and includes granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). In this study, we investigated granulocyte and monocyte subsets in a large cohort of AAV patients with emphasis on disease activity and tendency to relapse. A cohort of 105 patients with GPA or MPA and 126 healthy controls (HCs) were included. Clinical and laboratory data were collected for all patients, including disease activity, tendency to relapse, and pharmacological treatment. Using flow cytometry, circulating eosinophils, basophils, neutrophils, and monocytes were assessed. The monocytes were subdivided into classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14−CD16+) monocytes. Mature (CD16high) or newly released (CD16dim) neutrophils were defined, as well as the frequency of CD177+ neutrophils. AAV patients displayed increased frequencies of intermediate monocytes, mature and newly released neutrophils, and an expanded population of CD177+ neutrophils compared to HC. MPA patients differed from GPA patients in terms of lower frequency of classical monocytes. No differences in cell frequencies regarding ANCA phenotype were observed. Paired data from 23 patients demonstrated that active disease was associated with an increased frequency of mature neutrophils and a decreased frequency of monocytes, in particular intermediate monocytes. Moreover, GPA patients with a tendency to relapse displayed an increased frequency of mature neutrophils with increased expression of CD177+. Relapsing MPA patients, on the other hand, showed decreased frequency of intermediate monocytes. Finally, rituximab treatment was associated with increased frequencies of classical and intermediate monocytes. In conclusion, AAV patients exhibit a skewing of different neutrophil and monocyte subpopulations that are associated with disease subtypes, disease activity, rituximab treatment, and propensity to relapse. These changes may contribute to the inflammatory process and could potentially be used as biomarkers for relapse prediction.
{"title":"Disease Activity and Tendency to Relapse in ANCA-Associated Vasculitis Are Reflected in Neutrophil and Intermediate Monocyte Frequencies","authors":"Sofia Smargianaki, Evelina Elmér, Sandra Lilliebladh, Sophie Ohlsson, Åsa Pettersson, Thomas Hellmark, Åsa CM Johansson","doi":"10.1155/2024/6648265","DOIUrl":"https://doi.org/10.1155/2024/6648265","url":null,"abstract":"Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases with inflammation affecting small blood vessels and includes granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). In this study, we investigated granulocyte and monocyte subsets in a large cohort of AAV patients with emphasis on disease activity and tendency to relapse. A cohort of 105 patients with GPA or MPA and 126 healthy controls (HCs) were included. Clinical and laboratory data were collected for all patients, including disease activity, tendency to relapse, and pharmacological treatment. Using flow cytometry, circulating eosinophils, basophils, neutrophils, and monocytes were assessed. The monocytes were subdivided into classical (CD14<sup>++</sup>CD16<sup>−</sup>), intermediate (CD14<sup>++</sup>CD16<sup>+</sup>), and nonclassical (CD14<sup>−</sup>CD16<sup>+</sup>) monocytes. Mature (CD16<sup>high</sup>) or newly released (CD16<sup>dim</sup>) neutrophils were defined, as well as the frequency of CD177<sup>+</sup> neutrophils. AAV patients displayed increased frequencies of intermediate monocytes, mature and newly released neutrophils, and an expanded population of CD177<sup>+</sup> neutrophils compared to HC. MPA patients differed from GPA patients in terms of lower frequency of classical monocytes. No differences in cell frequencies regarding ANCA phenotype were observed. Paired data from 23 patients demonstrated that active disease was associated with an increased frequency of mature neutrophils and a decreased frequency of monocytes, in particular intermediate monocytes. Moreover, GPA patients with a tendency to relapse displayed an increased frequency of mature neutrophils with increased expression of CD177<sup>+</sup>. Relapsing MPA patients, on the other hand, showed decreased frequency of intermediate monocytes. Finally, rituximab treatment was associated with increased frequencies of classical and intermediate monocytes. In conclusion, AAV patients exhibit a skewing of different neutrophil and monocyte subpopulations that are associated with disease subtypes, disease activity, rituximab treatment, and propensity to relapse. These changes may contribute to the inflammatory process and could potentially be used as biomarkers for relapse prediction.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139083335","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}
Kong-kong Wei, Zhi-xing Du, Jun-ge Deng, Jin-wei Yang, Hao Chen
Background. Pyroptosis has a dual function in malignant tumor progression and management. The action of pyroptosis-related genes (PRGs) in pancreatic cancer (PC), however, remains uncertain. Methods. Differential expression analyses of 57 PRGs were conducted in the TCGA TARGET GTEx dataset. The candidate genes were determined using LASSO Cox regression and random forest analyses. A risk model was developed with the TCGA dataset and validated with the ICGC dataset. Results. Three prognosis-related PRGs (BAK1, GSDMC, and IL18) were chosen to create a risk model. High-risk patients from the TCGA and ICGC cohorts had an unfavorable overall survival (all ). The risk modelʼs accuracy and independent predictability were assessed by receiver operating characteristic curves and multivariate Cox regression analysis, respectively. High-risk patients possessed different molecular pathways, higher KRAS and TP53 mutations, increased expression of PD-L1, C1 immune subtype, and immunosuppressive microenvironment characterized by parainflammation compared to low-risk patients. KRAS and TP53 mutations participated in different inflammatory pathways and played different prognostic roles between the two risk groups. KRAS mutations in high-risk patients caused a more unfavorable prognosis than wild-type KRAS (
{"title":"A Novel Pyroptosis-Based Prognostic Model Correlated with the Parainflammatory Immune Microenvironment of Pancreatic Cancer","authors":"Kong-kong Wei, Zhi-xing Du, Jun-ge Deng, Jin-wei Yang, Hao Chen","doi":"10.1155/2023/8776892","DOIUrl":"https://doi.org/10.1155/2023/8776892","url":null,"abstract":"<i>Background</i>. Pyroptosis has a dual function in malignant tumor progression and management. The action of pyroptosis-related genes (PRGs) in pancreatic cancer (PC), however, remains uncertain. <i>Methods</i>. Differential expression analyses of 57 PRGs were conducted in the TCGA TARGET GTEx dataset. The candidate genes were determined using LASSO Cox regression and random forest analyses. A risk model was developed with the TCGA dataset and validated with the ICGC dataset. <i>Results</i>. Three prognosis-related PRGs (BAK1, GSDMC, and IL18) were chosen to create a risk model. High-risk patients from the TCGA and ICGC cohorts had an unfavorable overall survival (all <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> The risk modelʼs accuracy and independent predictability were assessed by receiver operating characteristic curves and multivariate Cox regression analysis, respectively. High-risk patients possessed different molecular pathways, higher KRAS and TP53 mutations, increased expression of PD-L1, C1 immune subtype, and immunosuppressive microenvironment characterized by parainflammation compared to low-risk patients. KRAS and TP53 mutations participated in different inflammatory pathways and played different prognostic roles between the two risk groups. KRAS mutations in high-risk patients caused a more unfavorable prognosis than wild-type KRAS (<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)\"></path></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,-0.013,3","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138825737","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}
DJ-1 is significantly elevated in various malignancies. However, the clinical significance of DJ-1 in hormone receptor (HR)-positive (HR+) breast cancer remains unclear. We evaluated DJ-1 expression in different databases and validated in vitro assay by RT-PCR and western blot among HR+ breast cancer. The correlations between DJ-1 level and tumor-immune were calculated. Mutational landscape, enriched signaling pathways, and drug sensitivity analyses were also assessed between DJ-1 high and low-expression groups. DJ-1 was upregulated in HR+ breast cancer, and high DJ-1 expression was significantly linked with poor prognosis. DJ-1 was correlated with the expression and function of different immune cells. The low DJ-1 group showed sensitivity to paclitaxel and docetaxel, while the high-expression group showed sensitivity to doxorubicin. CTLA4 and PD-L1 were more sensitive in high-DJ-1 group. It is involved in a range of pathways and might behave as a novel biomarker of prognostic value for the immune environment and drug sensitivity in HR+ breast cancer.
{"title":"DJ-1: A Potential Biomarker Related to Prognosis, Chemoresistance, and Expression of Microenvironmental Chemokine in HR-Positive Breast Cancer","authors":"Yinghong Xie, Yuancheng Li, Mengzhu Yang","doi":"10.1155/2023/5041223","DOIUrl":"https://doi.org/10.1155/2023/5041223","url":null,"abstract":"<i>DJ-1</i> is significantly elevated in various malignancies. However, the clinical significance of <i>DJ-1</i> in hormone receptor (HR)-positive (HR+) breast cancer remains unclear. We evaluated <i>DJ-1</i> expression in different databases and validated <i>in vitro</i> assay by RT-PCR and western blot among HR+ breast cancer. The correlations between <i>DJ-1</i> level and tumor-immune were calculated. Mutational landscape, enriched signaling pathways, and drug sensitivity analyses were also assessed between <i>DJ-1</i> high and low-expression groups. <i>DJ-1</i> was upregulated in HR+ breast cancer, and high <i>DJ-1</i> expression was significantly linked with poor prognosis. <i>DJ-1</i> was correlated with the expression and function of different immune cells. The low <i>DJ-1</i> group showed sensitivity to paclitaxel and docetaxel, while the high-expression group showed sensitivity to doxorubicin. CTLA4 and PD-L1 were more sensitive in high-<i>DJ-1</i> group. It is involved in a range of pathways and might behave as a novel biomarker of prognostic value for the immune environment and drug sensitivity in HR+ breast cancer.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138579994","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}
Liyan Chen, Xiaohui Yuan, Yaowei He, Zichuan Fan, Ya Guan, Qiuying Li, Yaying Chen, Lianglan Bao, Yidan Huang, Kefang Lai
Objective. Semaphorin3E (Sema3E) mediates reorganization of the actin cytoskeleton, and plays an important role in ensuring the specificity of synapse formation and angiogenesis. However, the role of Sema3E in allergic asthma (AS) and eosinophilic bronchitis (EB) is still elusive. This study aimed to investigate the relationship between Sema3E in vagal ganglion and lung tissue, airway reactivity, and eosinophilic inflammation. Methods. The frequency of coughs and airway reactivity as well as the airway inflammation were observed in ovalbumin- (OVA-) induced AS and EB mouse models. The expression of Sema3E was examined in the vagal ganglion and lung tissues by immunofluorescence staining and western blotting analyses. In the Sema3E treatment protocol, exogenous Sema3E was administrated intranasally before challenge in AS model to study the effect of Sema3E on airway hyperresponsiveness, airway inflammation, mucus production, and collagen deposition. Results. The similar higher frequency of coughs and airway eosinophilic inflammation could be seen in AS and EB groups compared with nasal saline (NS) and dexamethasone (DXM) groups. The absence of the airway hyperresponsiveness was observed in EB and DXM group, while AS group showed increase in airway reactivity to methacholine. The expression of Sema3E in vagal ganglion and lung tissue was remarkably decreased in AS and DXM group compared with EB group. Sema3E-treated asthma mice displayed ameliorated airway hyperresponsiveness, mucus production, and collagen deposition. Conclusion. Sema3E in lungs and vagal ganglia is related to eosinophilic inflammation and has a protective effect on OVA-induced AHR in asthma.
{"title":"The Expression of Semaphorin3E in Vagal Ganglion and Lung Tissue Is Related to Airway Hyperresponsiveness in Murine Asthma Model","authors":"Liyan Chen, Xiaohui Yuan, Yaowei He, Zichuan Fan, Ya Guan, Qiuying Li, Yaying Chen, Lianglan Bao, Yidan Huang, Kefang Lai","doi":"10.1155/2023/6459234","DOIUrl":"https://doi.org/10.1155/2023/6459234","url":null,"abstract":"<i>Objective</i>. Semaphorin3E (Sema3E) mediates reorganization of the actin cytoskeleton, and plays an important role in ensuring the specificity of synapse formation and angiogenesis. However, the role of Sema3E in allergic asthma (AS) and eosinophilic bronchitis (EB) is still elusive. This study aimed to investigate the relationship between Sema3E in vagal ganglion and lung tissue, airway reactivity, and eosinophilic inflammation. <i>Methods</i>. The frequency of coughs and airway reactivity as well as the airway inflammation were observed in ovalbumin- (OVA-) induced AS and EB mouse models. The expression of Sema3E was examined in the vagal ganglion and lung tissues by immunofluorescence staining and western blotting analyses. In the Sema3E treatment protocol, exogenous Sema3E was administrated intranasally before challenge in AS model to study the effect of Sema3E on airway hyperresponsiveness, airway inflammation, mucus production, and collagen deposition. <i>Results</i>. The similar higher frequency of coughs and airway eosinophilic inflammation could be seen in AS and EB groups compared with nasal saline (NS) and dexamethasone (DXM) groups. The absence of the airway hyperresponsiveness was observed in EB and DXM group, while AS group showed increase in airway reactivity to methacholine. The expression of Sema3E in vagal ganglion and lung tissue was remarkably decreased in AS and DXM group compared with EB group. Sema3E-treated asthma mice displayed ameliorated airway hyperresponsiveness, mucus production, and collagen deposition. <i>Conclusion</i>. Sema3E in lungs and vagal ganglia is related to eosinophilic inflammation and has a protective effect on OVA-induced AHR in asthma.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138566788","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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