Immunological Investigations最新文献

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MiR-519d-3p from Placenta-Derived Exosomes Induce Immune Intolerance Regulating Immune Cells, Contributing to the Pathogenesis of Preeclampsia. 来自胎盘来源外泌体的MiR-519d-3p诱导免疫不耐受调节免疫细胞,参与子痫前期的发病机制
IF 2.9 4区 医学
Immunological Investigations Pub Date : 2025-05-01 Epub Date: 2025-01-17 DOI: 10.1080/08820139.2025.2450234
Si-Qi Cao, Tu-Xiang Jiang, Ying-Ying Guo, Rong Lin, Liang Lin
{"title":"MiR-519d-3p from Placenta-Derived Exosomes Induce Immune Intolerance Regulating Immune Cells, Contributing to the Pathogenesis of Preeclampsia.","authors":"Si-Qi Cao, Tu-Xiang Jiang, Ying-Ying Guo, Rong Lin, Liang Lin","doi":"10.1080/08820139.2025.2450234","DOIUrl":"10.1080/08820139.2025.2450234","url":null,"abstract":"<p><strong>Background: </strong>MiR-519d-3p, also called specific placenta biomarkers, is a member of the Chromosome 19 miRNA Cluster (C19MC) with the highest concentrations of miRNAs in human placenta and maternal serum. These miRNAs are secreted by fetal trophoblast cells within extracellular vesicles (EVs) and interact with the mother's immune cells, which has been proposed to be crucial for immunological tolerance at the placental-maternal interface. A key mechanism in preeclampsia, a multifactorial, multipath hypertensive pregnancy illness, is an immunological imbalance between the mother and the fetus.</p><p><strong>Methods: </strong>Using Next Generation Sequencing, we determined that the placenta-derived Exosomes (pEXOs) of preeclamptic patients had elevated expression of miR-519. To further develop an in vitro model of trophoblast-immune cell communication, HTR-8/Svneo cells and Jurkat T cells were employed and we utilized experiments such as Western blot (WB), Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR), Cell-Counting-Kit-8 (CCK-8) cell proliferation analysis, cell apoptosis analysis, and other techniques to accomplish research.</p><p><strong>Results: </strong>It was discovered that miR-519d-3p in pEXOs promoted Jurkat T cell proliferation, inhibited apoptosis, and induced Jurkat T cell differentiation toward Th17.</p><p><strong>Conclusion: </strong>MiR-519d-3p in pEXOs disrupts immune tolerance at the maternal-placental interface by encouraging Jurkat T cell proliferation, preventing Jurkat T cell apoptosis, and creating an imbalance in Th17/Treg differentiation. This likely leads to SIRS and unfavorable pregnancy complications like preeclampsia.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"522-543"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Timosaponin A-III Alleviates Asthma-Induced Airway Inflammation, Th17 Cell Differentiation, and STAT3/RORγt Pathway. Timosaponin A-III缓解哮喘诱导的气道炎症、Th17细胞分化和STAT3/RORγt通路
IF 2.9 4区 医学
Immunological Investigations Pub Date : 2025-05-01 Epub Date: 2025-01-16 DOI: 10.1080/08820139.2025.2450239
Lijie Wang, Jiabo Yuan, Ruiqi Zhao, Congyao Wang, Zhuying Li
{"title":"Timosaponin A-III Alleviates Asthma-Induced Airway Inflammation, Th17 Cell Differentiation, and STAT3/RORγt Pathway.","authors":"Lijie Wang, Jiabo Yuan, Ruiqi Zhao, Congyao Wang, Zhuying Li","doi":"10.1080/08820139.2025.2450239","DOIUrl":"10.1080/08820139.2025.2450239","url":null,"abstract":"<p><strong>Introduction: </strong>T helper 17 (Th17) cells have a significant effect in the pathogenesis of asthma, and signal transducer and activator of transcription 3 (STAT3) pathway activation is critical for Th17 cell differentiation. Timosaponin A-III (TA3) was reported to inhibit the STAT3 pathway. Here, we investigated whether TA3 improved asthma by inhibiting the STAT3 pathway.</p><p><strong>Methods: </strong> Ovalbumin (OVA)-induced asthma murine models were developed, and TA3 (10 or 20 mg/kg) was gavage daily during OVA challenge. Murine naïve CD4<sup>+</sup>T cells were   triggered for Th17 differentiation, and TA3 (5 or 10 μM) was used to treat cells during induction of Th17 differentiation.</p><p><strong>Results: </strong><i>In vivo</i> experiments showed that TA3 decreased airway inflammation, goblet cell and smooth muscle hyperplasia, α-smooth muscle actin and collagen deposition, Th17 differentiation, and STAT3/RORγt signaling activation in mice exposed to OVA. The inhibitory effect of TA3 on STAT3/RORγt signaling activation was also observed in <i>in vitro</i> experiments. Compared to positive control static (a specific inhibitor of STAT3), TA3 had a similar effect on Th17 differentiation.</p><p><strong>Discussion: </strong>These findings indicate that TA3 may ameliorate Th17 cell differentiation by suppressing STAT3/RORγt signaling. Our data provide evidence of the potential benefits of TA3 for the treatment of asthma.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"544-559"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hirsutella sinensis Fungus Promotes CD8+ T Cell-Mediated Anti-Tumor Immunity by Affecting Tumor-Associated Macrophages-Derived CCRL2. 毛杆菌真菌通过影响肿瘤相关巨噬细胞衍生的CCRL2促进CD8+ T细胞介导的抗肿瘤免疫
IF 2.9 4区 医学
Immunological Investigations Pub Date : 2025-05-01 Epub Date: 2025-01-17 DOI: 10.1080/08820139.2025.2450246
Kaixiang Zhao, Yan Ma, Jing Luo, Yanhui Xu, Qiyang Shou, Hao Jiang, Xinhai Zhu
{"title":"<i>Hirsutella sinensis</i> Fungus Promotes CD8<sup>+</sup> T Cell-Mediated Anti-Tumor Immunity by Affecting Tumor-Associated Macrophages-Derived CCRL2.","authors":"Kaixiang Zhao, Yan Ma, Jing Luo, Yanhui Xu, Qiyang Shou, Hao Jiang, Xinhai Zhu","doi":"10.1080/08820139.2025.2450246","DOIUrl":"10.1080/08820139.2025.2450246","url":null,"abstract":"<p><strong>Introduction: </strong><i>Hirsutella sinensis</i> fungus (HSF)is an artificial substitute for <i>Cordyceps sinensis</i> and has shown promising therapeutic effects in various diseases including cancer. Previous studies have demonstrated that HSF can affect macrophage polarization and activate systemic immune response. In our preliminary experiments, we validated that HSF inhibited the proliferation of lung cancer (LC) cells, but the underlying mechanism is elusive. We intended to explore the mechanism of HSF in promoting anti-tumor immunity.</p><p><strong>Methods: </strong><i>In vivo</i> experiments were performed to confirm inhibitory effect of HSF on LC growth, and sequencing results revealed abnormal expression of CCRL2. Knockdown and overexpression of CCRL2 were conducted to investigate its effect on macrophage polarization, and co-culture with T cells was to assay the impact of HSF+CCRL2 on CD8<sup>+</sup> T cell activation by flow cytometry.</p><p><strong>Results: </strong>Overexpression of CCRL2 promoted macrophage polarization toward M1 and activated the proliferation and effector function of CD8<sup>+</sup> T cells. HSF promoted CCRL2 expression and affected M1 polarization via CCRL2, which in turn affected CD8<sup>+</sup> T cell-mediated anti-tumor immunity.</p><p><strong>Discussion: </strong>Our study demonstrated that HSF promoted macrophage M1 polarization and activated CD8<sup>+</sup> T cells via CCRL2, thereby inhibiting the progression of LC.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"573-588"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Innovative Approaches to Psoriasis: Small Molecules Targeting Key Signaling Pathways. 银屑病的创新方法:靶向关键信号通路的小分子。
IF 2.9 4区 医学
Immunological Investigations Pub Date : 2025-05-01 Epub Date: 2025-01-17 DOI: 10.1080/08820139.2025.2449960
Meeral Gosia, Gaurav Doshi, Siddhi Bagwe Parab, Angel Godad
{"title":"Innovative Approaches to Psoriasis: Small Molecules Targeting Key Signaling Pathways.","authors":"Meeral Gosia, Gaurav Doshi, Siddhi Bagwe Parab, Angel Godad","doi":"10.1080/08820139.2025.2449960","DOIUrl":"10.1080/08820139.2025.2449960","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis (Pso) is a chronic, immune-mediated dermatological condition characterized by dysregulated inflammatory responses and the hyperproliferation of keratinocytes. Biologics, which target specific cytokines such as IL-17 and IL-23, have revolutionized the management by addressing key drivers of its pathophysiology. Despite their efficacy, biologics are not without limitations, including the need for intermittent administration and ongoing monitoring. In contrast, small molecules offer a promising alternative by selectively inhibiting key signaling pathways that modulate pro-inflammatory cytokines involved in the inflammatory cascade.</p><p><strong>Methods and results: </strong>This review suggests a new therapeutic strategy for Pso treatment, emphasizing the intricate relationships between small molecules and important signaling pathways involved in the pathophysiology of skin conditions. Improving treatment outcomes and reducing the side effects associated with conventional medicines, this review aims to better understand how tailored small-molecule inhibitors might efficiently control these pathways. This creative approach promotes the creation of individualized treatment plans that can greatly enhance the quality of life of patients with Psoby utilizing the knowledge gathered from recent developments in signaling pathway research.</p><p><strong>Conclusion: </strong>This review delves into the molecular mechanisms underlying Pso and explores how small molecules can be harnessed to enhance treatment outcomes, presenting a new paradigm for managing this chronic skin disorder.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"457-493"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Mechanism of Baicalin in the Treatment of Mycoplasma Pneumoniae Pneumonia by Regulating NLRP3/Caspase-1 Signaling Pathway. 黄芩苷通过调节NLRP3/Caspase-1信号通路治疗肺炎支原体肺炎的机制
IF 2.9 4区 医学
Immunological Investigations Pub Date : 2025-05-01 Epub Date: 2025-01-09 DOI: 10.1080/08820139.2025.2450244
Dan Song, Wenfeng Wei, Jie Zhang, Lu Zhang, Weiming Wang, Jinhai Huo
{"title":"The Mechanism of Baicalin in the Treatment of Mycoplasma Pneumoniae Pneumonia by Regulating NLRP3/Caspase-1 Signaling Pathway.","authors":"Dan Song, Wenfeng Wei, Jie Zhang, Lu Zhang, Weiming Wang, Jinhai Huo","doi":"10.1080/08820139.2025.2450244","DOIUrl":"10.1080/08820139.2025.2450244","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated the mechanism of baicalin (BIA) attenuating the inflammatory response and lung injury in mycoplasma pneumoniae pneumonia (MPP) mice.</p><p><strong>Methods: </strong>MPP mouse models were established and then treated with BIA, azithromycin, or NLRP3 inflammasome activator. Lung wet-to-dry weight (W/D) ratio were weighed. Serum levels of MP-IgM, C-reactive protein (CRP) and bronchoalveolar lavage fluid (BALF) protein were detected by kits, NLRP3/Caspase-1 pathway-related protein levels by Western blot, and IL-1β, IL-18, IL-6 and TNF-α levels by ELISA. HE staining was performed to detect lung injury.</p><p><strong>Results: </strong>MPP mice showed elevated mouse lung W/D ratio, upregulated serum MP-IgM and CRP levels and BALF protein, and enhanced IL-6 and TNF-α levels, which were reversed by BIA or azithromycin treatment, suggesting that BIA attenuated pulmonary inflammatory response in MPP mice. The lung tissue of MPP mice showed upregulated NLRP3, cleaved Caspase-1,Caspase-1, GSDMD-N and GSDMD levels and raised IL-1β and IL-18 levels, and changes were annulled by BIA or azithromycin treatment, suggesting that BIA inhibited the NLRP3/Caspase-1 pathway activation. NLRP3/Caspase-1 pathway activation partially abrogated the alleviative effect of BIA on the pulmonary inflammatory response of MPP mice.</p><p><strong>Conclusion: </strong>BIA mitigates inflammatory response and lung injury in MPP mice by inhibiting NLRP3/Caspase-1 pathway activation.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"560-572"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunomodulatory Effects of Pterocarpanquinone LQB-118 in Murine Peritoneal Macrophages. pterocarpan醌LQB-118对小鼠腹腔巨噬细胞的免疫调节作用。
IF 2.9 4区 医学
Immunological Investigations Pub Date : 2025-05-01 Epub Date: 2025-01-08 DOI: 10.1080/08820139.2025.2449949
Éssia de Almeida Lima, Luiz Henrique Agra Cavalcante-Silva, Deyse Cristina Madruga Carvalho, Mariana Mendonça Soares, Anna Beatriz Araujo Medeiros, Chaquip Daher Netto, Paulo Roberto Ribeiro Costa, Sandra Rodrigues-Mascarenhas
{"title":"Immunomodulatory Effects of Pterocarpanquinone LQB-118 in Murine Peritoneal Macrophages.","authors":"Éssia de Almeida Lima, Luiz Henrique Agra Cavalcante-Silva, Deyse Cristina Madruga Carvalho, Mariana Mendonça Soares, Anna Beatriz Araujo Medeiros, Chaquip Daher Netto, Paulo Roberto Ribeiro Costa, Sandra Rodrigues-Mascarenhas","doi":"10.1080/08820139.2025.2449949","DOIUrl":"10.1080/08820139.2025.2449949","url":null,"abstract":"<p><strong>Background: </strong>Phagocytosis is an important function of macrophages. However, when it's dysregulated, it could compromise homeostasis. Thus, this study aimed to assess the inhibitory activity of pterocarpanquinone LQB 118 on murine macrophage phagocytosis.</p><p><strong>Methods: </strong>We used peritoneal macrophages isolated from mice to evaluate the impact of LQB 118 (5 μM) on the modulation of phagocytic activity and possible action mechanism related: IL-12 (by ELISA), NO (by Griess reaction),ROS production (by flow cytometry), and intracellular signaling proteins (iNOS, P-Akt, P-mTOR, NF-κB, and P-NF-κB) (by flow cytometry).The macrophages were stimulated with zymosan to assess both phagocytic activity and flow cytometry assays.</p><p><strong>Results: </strong>Treatment with LQB 118 resulted in a reduction in the phagocytosis of zymosan particles by macrophages. This effect could potentially be attributed to LQB's inhibition of IL-12 production and mTOR/NF-κB signaling. Furthermore, LQB 118 decreased the levels of ROS and NO without interfering with iNOS and Akt activation.</p><p><strong>Conclusion: </strong>These findings show the anti-phagocytic activity of LQB 118 on macrophage, highlighting the potential of this compound as a candidate for modulating macrophage-driven inflammation.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"494-505"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Application of the Monoclonal Autoantibody and Its Target Protein Derived from the Peripheral Blood of SLE Patients in Serological Diagnosis and Differential Diagnosis of SLE. SLE患者外周血单克隆自身抗体及其靶蛋白在SLE血清学诊断和鉴别诊断中的应用
IF 2.9 4区 医学
Immunological Investigations Pub Date : 2025-05-01 Epub Date: 2025-01-22 DOI: 10.1080/08820139.2025.2449961
Keting Jin, Yalun Chen, Yuyang Ye, Qiang Ke, Jinhui Hong, Kaibo Zhang, Leping Wang, Jialu Ye, Jiawen Dong, Yongchao Xu, Jiali Shan, Wenshan Zhao, Yi Zhang, Jing Wu
{"title":"Application of the Monoclonal Autoantibody and Its Target Protein Derived from the Peripheral Blood of SLE Patients in Serological Diagnosis and Differential Diagnosis of SLE.","authors":"Keting Jin, Yalun Chen, Yuyang Ye, Qiang Ke, Jinhui Hong, Kaibo Zhang, Leping Wang, Jialu Ye, Jiawen Dong, Yongchao Xu, Jiali Shan, Wenshan Zhao, Yi Zhang, Jing Wu","doi":"10.1080/08820139.2025.2449961","DOIUrl":"10.1080/08820139.2025.2449961","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with limited reliable diagnostic biomarkers. This study evaluates the utility of DEAD-box helicase 5 (DDX5) as a diagnostic and differential marker for SLE and assesses the performance of a capture bead-based flow cytometry (CBFCM) method for detecting serum proteins.</p><p><strong>Method: </strong>Serum samples were collected from 52 patients with SLE, 38 patients with rheumatoid arthritis (RA), 49 patients with lung cancer (LC), and 50 healthy controls (HCs). Levels of DDX5, anti-DDX5, anti-dsDNA, and anti-Sm were quantified using enzyme-linked immunosorbent assay (ELISA) and CBFCM.</p><p><strong>Results: </strong>Serum DDX5 levels were significantly elevated in patients with SLE compared to patients with RA and HCs, correlating with the SLE activity. DDX5 demonstrated strong discriminatory power between SLE and RA. Combining DDX5, anti-dsDNA, and anti-Sm as biomarkers yielded an area under the curve (AUC) of 0.976 for SLE diagnosis. Decision curve analysis indicated a high clinical benefit from the combined biomarkers. The sensitivity and specificity of DDX5 were 66.11% and 88.89% for ELISA, and 72% and 91.3% for CBFCM.</p><p><strong>Discussion: </strong>DDX5 shows promise as a novel serological biomarker for SLE diagnosis and differential diagnosis. Additionally, CBFCM outperforms ELISA in detecting soluble serum proteins.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"506-521"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tissue-Resident Memory T Cells in Tumor Immunity and Immunotherapy of Digestive System Tumors. 组织驻留记忆T细胞在肿瘤免疫和消化系统肿瘤免疫治疗中的作用。
IF 2.9 4区 医学
Immunological Investigations Pub Date : 2025-05-01 Epub Date: 2025-01-22 DOI: 10.1080/08820139.2024.2447780
Min Cheng, Jie Liu, Yue Liang, Jiamei Xu, Lin Ma, Jing Liang
{"title":"Tissue-Resident Memory T Cells in Tumor Immunity and Immunotherapy of Digestive System Tumors.","authors":"Min Cheng, Jie Liu, Yue Liang, Jiamei Xu, Lin Ma, Jing Liang","doi":"10.1080/08820139.2024.2447780","DOIUrl":"10.1080/08820139.2024.2447780","url":null,"abstract":"<p><strong>Background: </strong>Tissue-resident memory T (TRM) cells possess unique abilities to migrate, establish themselves in tissues, and monitor peripheral tissues without circulating. They are crucial in providing long-lasting and local immune protection against surface infections. TRMs demonstrate distinct phenotypic and functional characteristics compared to central memory T (Tcm) cells and effector memory T (Tem) cells.</p><p><strong>Methods: </strong>We reviewed a large number of literature to explore the physiological and functional roles of tissue-resident memory T cells, as well as the link between TRM cells and the development and prognosis of digestive tract tumors. We also investigated the association between TRM cells, intestinal flora, and metabolites.</p><p><strong>Results: </strong>Recent studies have implicated TRMs in the immune response against tumors, making them a potential target for cancer therapy. However, research specifically focused on gastrointestinal tumors is limited.</p><p><strong>Conclusion: </strong>This review aims to compile and assess the most recent data on the role of TRM cells in gastrointestinal tumor immunity. Additionally, it explores recent advancements in immunotherapy and investigates how TRMs may influence intestinal flora and metabolites.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"435-456"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NK Cell Exosomes Alleviate PD-L1 Expression and Facilitate Tumor Immunity by Repressing PI3K-AKT-mTOR Signaling. NK细胞外泌体通过抑制PI3K-AKT-mTOR信号通路减轻PD-L1表达,促进肿瘤免疫。
IF 2.9 4区 医学
Immunological Investigations Pub Date : 2025-04-01 Epub Date: 2025-01-02 DOI: 10.1080/08820139.2024.2445608
Hang Xie, Yujie Wu, Jingyao Huang, Quan Shen, Xiaoyan Li, Lili Wang, Junqing Lin, Zhen Chi, Kun Ke, Xin Lin, Rong Chen, Rihua Liao, Yong Li, Ning Huang
{"title":"NK Cell Exosomes Alleviate PD-L1 Expression and Facilitate Tumor Immunity by Repressing PI3K-AKT-mTOR Signaling.","authors":"Hang Xie, Yujie Wu, Jingyao Huang, Quan Shen, Xiaoyan Li, Lili Wang, Junqing Lin, Zhen Chi, Kun Ke, Xin Lin, Rong Chen, Rihua Liao, Yong Li, Ning Huang","doi":"10.1080/08820139.2024.2445608","DOIUrl":"10.1080/08820139.2024.2445608","url":null,"abstract":"<p><strong>Background: </strong>Liver cancer (LC) is a deadly malignancy with limited therapeutic options in recent years. Natural killer cell-derived exosomes (NK-exo), as an important bridge of information transmission between cells, also have a certain killing effect on tumor cells. On this basis, this study investigated the specific regulatory mechanism of NK-exo on LC cells.</p><p><strong>Methods: </strong>NK-exo was collected by differential centrifugation. The diameter and size distribution were characterized by dynamic light scattering (DLS), respectively. Western Blot (WB) assay detected the expression levels of exosome marker protein, PD-L1, and PI3K-AKT-mTOR signal-related proteins. The effect of NK-exo treatment on LC cell viability was measured by the CCK-8. With the use of CFDA·SE, we assessed the proliferation ability of CD8<sup>+</sup>T cells in direct co-culture with LC cells. The content of cytokines secreted by CD8<sup>+</sup>T cells in each treatment group was determined by enzyme-linked immunosorbent assay (ELISA) kits. We employed flow cytometry to analyze the expression of PD-L1 protein on the surface of LC cells and CD8 level in mice tumor tissues.</p><p><strong>Results: </strong>CCK-8 assay demonstrated that NK-exo repressed the cell viability of LC cells. WB uncovered that the protein expressions of PD-L1, p-AKT, and p-mTOR in NK-exo treated LC cells were decreased, which was returned to the control level after the addition of PI3K agonist. When NK-exo-treated LC cells were directly co-cultivated with CD8<sup>+</sup>T cells, the proliferation ability and cytokine secretion content of T cells were considerably elevated, and the expression of PD-L1 on LC cell surface was considerably reduced. However, these effects were restored to control levels by PI3K agonists.The in vivo experiments also confirmed that NK-exo could effectively inhibit the progression of LC, and the PI3K agonist could restore this effect to the level of the control group.</p><p><strong>Conclusion: </strong>This study provided the first evidence that exosomes derived from NK cells inhibited the PI3K-AKT-mTOR signaling pathway in LC cells, and reduced PD-L1 expression, thereby promoting tumor immunity. In comparison to traditional immune checkpoint inhibitors, NK-exo possessed unique mechanisms of action and potential advantages. NK-exo holds the promise of becoming an innovative immunotherapy for the treatment of LC.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"382-395"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Role of Exosomes in Central Immune Tolerance and Myasthenia Gravis. 外泌体在中枢免疫耐受和重症肌无力中的作用
IF 2.9 4区 医学
Immunological Investigations Pub Date : 2025-04-01 Epub Date: 2024-12-16 DOI: 10.1080/08820139.2024.2440772
Hanlu Zhang, Siyuan Luan, Fuqiang Wang, Lin Yang, Sicheng Chen, Zhiyang Li, Xuyang Wang, Wen-Ping Wang, Long-Qi Chen, Yun Wang
{"title":"The Role of Exosomes in Central Immune Tolerance and Myasthenia Gravis.","authors":"Hanlu Zhang, Siyuan Luan, Fuqiang Wang, Lin Yang, Sicheng Chen, Zhiyang Li, Xuyang Wang, Wen-Ping Wang, Long-Qi Chen, Yun Wang","doi":"10.1080/08820139.2024.2440772","DOIUrl":"10.1080/08820139.2024.2440772","url":null,"abstract":"<p><strong>Background: </strong>Immune homeostasis plays a crucial role in immunology andis dependent on both central and peripheral tolerance. Centraltolerance and peripheral tolerance occur in the thymus and thesecondary lymphoid tissues, respectively. Tolerance breakdown andimmune regulation defects can lead to autoimmune disorders. In thisreview article, we aimed to describe the role of exosomes inregulating central tolerance and provide a summary of their effectson the pathogenesis, diagnosis, and therapeutic potential inmyasthenia gravis (MG).</p><p><strong>Methods: </strong>Articles for this review wereidentified using the PubMed database.</p><p><strong>Results: </strong>As the primarylymphoid organ, the thymus is responsible for building an immunecompetent, yet self-tolerant of T-cell population. Thymic statesinclude thymoma, thymic hyperplasia, and thymic atrophy, which canexert a significant influence on the central immune tolerance andrepresent specific characteristics of MG. Previous studies have foundthat exosomes derived from human thymic epithelial cells carryantigen-presenting molecules and a wide range of tissue restrictedantigens, which may indicate a vital role of thymic exosomes in MG.Besides, exosomal miRNAs and lncRNAs may also play a critical role inthe pathophysiology of MG.</p><p><strong>Conclusion: </strong>This review provides thetherapeutic and diagnostic potential of exosomes in MG patients.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"412-434"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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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