Pub Date : 2025-04-21DOI: 10.1016/j.imbio.2025.152902
Jing Xie , Nan Xie , Chang Liu , Zhemin Huang , Min Du , Hao Hu , Kang Zheng , Jiaofeng Peng , Ranhui Li
The pathogenesis of Ureaplasma urealyticum infection is linked to the host inflammatory response; however, the specific molecular mechanisms underlying this phenomenon have not been fully elucidated. GrpE is a chaperonin that accelerates ADP release and ATP binding to DnaK, thereby enhancing the chaperone function of the HSP70 system under stress. However, alternative activities such as pro-inflammatory responses remain poorly understood. In this study, we report that the U. urealyticum GrpE exerts as a cytokine-inducing virulence factor toward macrophages. Using gene-knockout mice and specific inhibitors, we found that GrpE-induced pro-inflammatory cytokine expression was mediated by the TLR2/STAT3 pathway. We also found that glycolysis was essential for this pro-inflammatory response. Mechanistically, GrpE treatment stimulated STAT3-dependent accumulation of citric acid and acetyl-CoA, promoting histone acetylation and potent pro-inflammatory responses. Our results indicate that glycolysis plays a role in the inflammatory response induced by GrpE through the TLR2/STAT3 pathway and contributes to the glycolysis-mediated inflammatory response, offering a fresh understanding of the development of U. urealyticum infection.
{"title":"Ureaplasma urealyticum GrpE protein elicits glycolysis-mediated inflammatory responses through TLR2 in macrophages","authors":"Jing Xie , Nan Xie , Chang Liu , Zhemin Huang , Min Du , Hao Hu , Kang Zheng , Jiaofeng Peng , Ranhui Li","doi":"10.1016/j.imbio.2025.152902","DOIUrl":"10.1016/j.imbio.2025.152902","url":null,"abstract":"<div><div>The pathogenesis of <em>Ureaplasma urealyticum</em> infection is linked to the host inflammatory response; however, the specific molecular mechanisms underlying this phenomenon have not been fully elucidated. GrpE is a chaperonin that accelerates ADP release and ATP binding to DnaK, thereby enhancing the chaperone function of the HSP70 system under stress. However, alternative activities such as pro-inflammatory responses remain poorly understood. In this study, we report that the <em>U. urealyticum</em> GrpE exerts as a cytokine-inducing virulence factor toward macrophages. Using gene-knockout mice and specific inhibitors, we found that GrpE-induced pro-inflammatory cytokine expression was mediated by the TLR2/STAT3 pathway. We also found that glycolysis was essential for this pro-inflammatory response. Mechanistically, GrpE treatment stimulated STAT3-dependent accumulation of citric acid and acetyl-CoA, promoting histone acetylation and potent pro-inflammatory responses. Our results indicate that glycolysis plays a role in the inflammatory response induced by GrpE through the TLR2/STAT3 pathway and contributes to the glycolysis-mediated inflammatory response, offering a fresh understanding of the development of <em>U. urealyticum</em> infection.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152902"},"PeriodicalIF":2.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860148","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}
Pub Date : 2025-04-08DOI: 10.1016/j.imbio.2025.152900
Ziwen Li , Min Li , Sinuo Sun , Yu Bin , Suwei Zuo , Ronghua Huo , Jiayin Song , Gang Xue , Xu Lin , Jingfang Wu
Background
Previous studies have found that Apolipoprotein E (APOE) plays a crucial role in invasion and migration of papillary thyroid carcinoma (PTC) cells and enhance M2 macrophage polarization. Ferroptosis has been implicated in development of various tumors and their treatment resistance, and studies have shown that APOE is involved in ferroptosis regulation. However, whether APOE promotes PTC progression through ferroptosis modulation remains unclear. This study aims to investigate the ferroptosis-related mechanisms through which APOE facilitates cell invasion, migration, and macrophage polarization in PTC.
Methods
The expression levels of APOE, Sodium-dependent cystine/glutamate exchanger (xCT), Glutathione Peroxidase 4 (GPX4), Ferritin Heavy Chain 1 (FTH1), and Fe2+ in PTC tissues were detected using immunohistochemistry, Prussian blue staining, and western blot. The effects and mechanisms of APOE on ferroptosis were further examined through a series of experiments, including immunofluorescence, electron microscopy, RT-qPCR, western blot, and colorimetric assays. Additionally, In vivo experiments were conducted to assess the effect of APOE silencing on ferroptosis. The interaction between ferroptosis and macrophages in regulating PTC cell invasion and migration was validated using assays.co-culture systems, wound healing assays, and Transwell migration assays.
Results
In PTC tissues, Fe2+ accumulation was lower than in adjacent normal tissues, while the expression of APOE, xCT, GPX4, and FTH1 was significantly higher compared to adjacent normal tissues. Functional assays demonstrated that APOE inhibited ferroptosis in PTC cells, potentially by regulating ferroptosis through the PI3K/AKT1 pathway and modulating Fe2+ accumulation. Furthermore, APOE enhanced the invasion and migration abilities of PTC cells by promoting M2 macrophage polarization via ferroptosis inhibition.
Conclusion
This study reveals that APOE regulates ferroptosis through the PI3K/AKT1 pathway, thereby driving macrophage polarization toward the M2 phenotype, which in turn promotes the invasion and migration of PTC.
{"title":"APOE modulates ferroptosis to drive macrophage polarization toward the M2 type and enhance PTC migration and invasion","authors":"Ziwen Li , Min Li , Sinuo Sun , Yu Bin , Suwei Zuo , Ronghua Huo , Jiayin Song , Gang Xue , Xu Lin , Jingfang Wu","doi":"10.1016/j.imbio.2025.152900","DOIUrl":"10.1016/j.imbio.2025.152900","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have found that Apolipoprotein E (APOE) plays a crucial role in invasion and migration of papillary thyroid carcinoma (PTC) cells and enhance M2 macrophage polarization. Ferroptosis has been implicated in development of various tumors and their treatment resistance, and studies have shown that APOE is involved in ferroptosis regulation. However, whether APOE promotes PTC progression through ferroptosis modulation remains unclear. This study aims to investigate the ferroptosis-related mechanisms through which APOE facilitates cell invasion, migration, and macrophage polarization in PTC.</div></div><div><h3>Methods</h3><div>The expression levels of APOE, Sodium-dependent cystine/glutamate exchanger (xCT), Glutathione Peroxidase 4 (GPX4), Ferritin Heavy Chain 1 (FTH1), and Fe<sup>2+</sup> in PTC tissues were detected using immunohistochemistry, Prussian blue staining, and western blot. The effects and mechanisms of APOE on ferroptosis were further examined through a series of experiments, including immunofluorescence, electron microscopy, RT-qPCR, western blot, and colorimetric assays. Additionally, In vivo experiments were conducted to assess the effect of APOE silencing on ferroptosis. The interaction between ferroptosis and macrophages in regulating PTC cell invasion and migration was validated using assays.co-culture systems, wound healing assays, and Transwell migration assays.</div></div><div><h3>Results</h3><div>In PTC tissues, Fe<sup>2+</sup> accumulation was lower than in adjacent normal tissues, while the expression of APOE, xCT, GPX4, and FTH1 was significantly higher compared to adjacent normal tissues. Functional assays demonstrated that APOE inhibited ferroptosis in PTC cells, potentially by regulating ferroptosis through the PI3K/AKT1 pathway and modulating Fe<sup>2+</sup> accumulation. Furthermore, APOE enhanced the invasion and migration abilities of PTC cells by promoting M2 macrophage polarization via ferroptosis inhibition.</div></div><div><h3>Conclusion</h3><div>This study reveals that APOE regulates ferroptosis through the PI3K/AKT1 pathway, thereby driving macrophage polarization toward the M2 phenotype, which in turn promotes the invasion and migration of PTC.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152900"},"PeriodicalIF":2.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839776","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}
Pub Date : 2025-04-04DOI: 10.1016/j.imbio.2025.152899
Heng Zhang , Yiwen Yu , Minglei Jiang , Renquan Lu , Lin Guo
Objective
This study aim to explore the alterations of circulating T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in the peripheral blood of patients with papillary thyroid carcinoma (PTC), assess their association with PTC and the influence on B cells, and evaluate their diagnostic potential.
Methods
Peripheral blood samples were collected from 76 newly diagnosed PTC patients and 21 matched healthy controls between June 2023 and June 2024. Flow cytometry was used to determine the proportions of circulating Tfh and Tfr cells. The relationships between these cell populations and variables such as sex, age, and disease stage were analyzed. The diagnostic performance of circulating Tfh and Tfr cells, individually and in combination, was assessed using receiver operating characteristic (ROC) curves.
Results
Compared to healthy controls, PTC patients exhibited an increased proportion of circulating Tfh cells and a decrease proportion of Tfr cells. While the increase in Tfh cells was not subtype-specific, the proportions of Th1-like and Th17-like Tfr subtypes were significantly altered in the PTC group. The proportion of Tfr cells remained unaffected by sex or age, whereas the increase in Tfh cells was more pronounced in male and elderly patients. Although no significant differences were observed across disease stages, changes in Tfh and Tfr cell proportions correlated with B cell subtypes and certain thyroid-related indicators. ROC plots showed circulating Tfr cells had higher sensitivity and specificity for distinguishing PTC compared to Tfh cells or their combination.
{"title":"Circulating Tfh cells and Tfr cells in papillary thyroid carcinoma and their diagnostic potential","authors":"Heng Zhang , Yiwen Yu , Minglei Jiang , Renquan Lu , Lin Guo","doi":"10.1016/j.imbio.2025.152899","DOIUrl":"10.1016/j.imbio.2025.152899","url":null,"abstract":"<div><h3>Objective</h3><div>This study aim to explore the alterations of circulating T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in the peripheral blood of patients with papillary thyroid carcinoma (PTC), assess their association with PTC and the influence on B cells, and evaluate their diagnostic potential.</div></div><div><h3>Methods</h3><div>Peripheral blood samples were collected from 76 newly diagnosed PTC patients and 21 matched healthy controls between June 2023 and June 2024. Flow cytometry was used to determine the proportions of circulating Tfh and Tfr cells. The relationships between these cell populations and variables such as sex, age, and disease stage were analyzed. The diagnostic performance of circulating Tfh and Tfr cells, individually and in combination, was assessed using receiver operating characteristic (ROC) curves.</div></div><div><h3>Results</h3><div>Compared to healthy controls, PTC patients exhibited an increased proportion of circulating Tfh cells and a decrease proportion of Tfr cells. While the increase in Tfh cells was not subtype-specific, the proportions of Th1-like and Th17-like Tfr subtypes were significantly altered in the PTC group. The proportion of Tfr cells remained unaffected by sex or age, whereas the increase in Tfh cells was more pronounced in male and elderly patients. Although no significant differences were observed across disease stages, changes in Tfh and Tfr cell proportions correlated with B cell subtypes and certain thyroid-related indicators. ROC plots showed circulating Tfr cells had higher sensitivity and specificity for distinguishing PTC compared to Tfh cells or their combination.</div></div><div><h3>Conclusion</h3><div>PTC patients showed changed circulating Tfh cells and Tfr cells, presenting diagnostic potential.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152899"},"PeriodicalIF":2.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817206","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}
Pub Date : 2025-03-28DOI: 10.1016/j.imbio.2025.152898
Lizhong Zhang , Hongyi Li , Lei Shi , Jie Geng , Haojun Zhang , Haoran Chen , Peng Zhao , Yang Xiao , Jinqi Lu , Zhilun Li , Hongbin Pu , Chuandong Hou , Chenghui Li , Chumeng Gao , Xia Song , Zhuocheng Bao , Bing Zhai , Bo Guo , Bo Yang , Xuechun Lu , Qi Yu
During the COVID-19 pandemic, extensive research focused on universal treatments, but few studies addressed treatment regimens for elderly patients. This study aimed to evaluate the effects of etanercept, a TNF inhibitor, in elderly individuals with COVID-19 through observational analysis of compassionate use cases. The results showed that after one month of etanercept treatment, clinical indicators such as C-reactive protein, D-dimer, and fibrinogen normalised, whereas the control group receiving conventional treatment did not fully recover. Single-cell sequencing was performed on seven patients treated with etanercept and two uninfected individuals. Based on our data and in conjunction with external data, a comprehensive characterization map involving 400,000 cells was created. Transcriptomic analysis revealed autoimmune-like manifestations in elderly patients, highlighting the importance of immunotherapy. Plasma cells, platelets, and B cells were the most treatment-sensitive cells. Analysis of five drug types, including antiviral, etanercept, glucocorticoids, tocilizumab, and others, showed that tocilizumab was associated with an increased thrombosis risk in elderly patients. Meanwhile, etanercept alleviated autoimmune-like manifestations by inhibiting platelet factor 4 and suppressing TNF-α. Molecular docking showed etanercept's strong affinity (−15.0 kcal/mol) for the spike protein of the SARS-CoV-2 Omicron variant, suggesting it may protect immune-compromised patients. Our findings support etanercept as a potential treatment for elderly COVID-19 patients with autoimmune-like manifestations.
{"title":"Mechanism and Efficacy of Etanercept in Treating Autoimmune-like Manifestations of Coronavirus Disease 2019 in elderly individuals","authors":"Lizhong Zhang , Hongyi Li , Lei Shi , Jie Geng , Haojun Zhang , Haoran Chen , Peng Zhao , Yang Xiao , Jinqi Lu , Zhilun Li , Hongbin Pu , Chuandong Hou , Chenghui Li , Chumeng Gao , Xia Song , Zhuocheng Bao , Bing Zhai , Bo Guo , Bo Yang , Xuechun Lu , Qi Yu","doi":"10.1016/j.imbio.2025.152898","DOIUrl":"10.1016/j.imbio.2025.152898","url":null,"abstract":"<div><div>During the COVID-19 pandemic, extensive research focused on universal treatments, but few studies addressed treatment regimens for elderly patients. This study aimed to evaluate the effects of etanercept, a TNF inhibitor, in elderly individuals with COVID-19 through observational analysis of compassionate use cases. The results showed that after one month of etanercept treatment, clinical indicators such as C-reactive protein, D-dimer, and fibrinogen normalised, whereas the control group receiving conventional treatment did not fully recover. Single-cell sequencing was performed on seven patients treated with etanercept and two uninfected individuals. Based on our data and in conjunction with external data, a comprehensive characterization map involving 400,000 cells was created. Transcriptomic analysis revealed autoimmune-like manifestations in elderly patients, highlighting the importance of immunotherapy. Plasma cells, platelets, and B cells were the most treatment-sensitive cells. Analysis of five drug types, including antiviral, etanercept, glucocorticoids, tocilizumab, and others, showed that tocilizumab was associated with an increased thrombosis risk in elderly patients. Meanwhile, etanercept alleviated autoimmune-like manifestations by inhibiting platelet factor 4 and suppressing TNF-α. Molecular docking showed etanercept's strong affinity (−15.0 kcal/mol) for the spike protein of the SARS-CoV-2 Omicron variant, suggesting it may protect immune-compromised patients. Our findings support etanercept as a potential treatment for elderly COVID-19 patients with autoimmune-like manifestations.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152898"},"PeriodicalIF":2.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giardia duodenalis is a globally distributed zoonotic parasite primarily transmitted through the fecal-oral route, infecting various vertebrates, and the infection of which is prevalent in goats. Immune cells play a crucial role in pathogens invasion, and neutrophil extracellular traps (NETs) released by neutrophils serve as a non-specific defense mechanism against pathogens including parasites. In this study, we investigated the characteristics, components, and molecular mechanisms of goat NETs upon stimulation with G. duodenalis trophozoites. This study demonstrates that G. duodenalis trigger dose-dependent NETs formation in goat neutrophils, composed of DNA, citrullinated histone H3 (CitH3), and neutrophil elastase (NE). Reactive oxygen species (ROS) accumulation synchronizes with NETosis during G. duodenalis infection. Inhibitor experiments confirmed that G. duodenalis-induced NETs and ROS production depend on TLR2/4 signaling and require NADPH oxidase (NOX), ERK1/2, and p38 MAPK activation. This work identifies TLR2/4, NOX, ERK1/2, and p38 MAPK pathways as key regulators of NETs/ROS coordination during G. duodenalis infection, providing the first evidence of G. duodenalis-triggered NETs in goats. The findings highlight NETs as critical components of anti-G. duodenalis immunity and suggest potential for NETs-targeted therapeutic strategies.
{"title":"Giardia duodenalis triggered neutrophil extracellular traps in goats","authors":"Xi Jiang , Qiaoyu Li , Rongsheng Huang , Yuxiao Qian, Yuqian Jiang, Tingting Liu, Yiwen Wang, Kairao Hu, Jing Huang, Wenlong Huang, Quan Liu, Zhengkai Wei, Haoji Zhang, Xingang Yu","doi":"10.1016/j.imbio.2025.152894","DOIUrl":"10.1016/j.imbio.2025.152894","url":null,"abstract":"<div><div><em>Giardia duodenalis</em> is a globally distributed zoonotic parasite primarily transmitted through the fecal-oral route, infecting various vertebrates, and the infection of which is prevalent in goats. Immune cells play a crucial role in pathogens invasion, and neutrophil extracellular traps (NETs) released by neutrophils serve as a non-specific defense mechanism against pathogens including parasites. In this study, we investigated the characteristics, components, and molecular mechanisms of goat NETs upon stimulation with <em>G. duodenalis</em> trophozoites. This study demonstrates that <em>G. duodenalis</em> trigger dose-dependent NETs formation in goat neutrophils, composed of DNA, citrullinated histone H3 (CitH3), and neutrophil elastase (NE). Reactive oxygen species (ROS) accumulation synchronizes with NETosis during <em>G. duodenalis</em> infection. Inhibitor experiments confirmed that <em>G. duodenalis</em>-induced NETs and ROS production depend on TLR2/4 signaling and require NADPH oxidase (NOX), ERK<sub>1/2</sub>, and p38 MAPK activation. This work identifies TLR2/4, NOX, ERK<sub>1/2</sub>, and p38 MAPK pathways as key regulators of NETs/ROS coordination during <em>G. duodenalis</em> infection, providing the first evidence of <em>G. duodenalis</em>-triggered NETs in goats. The findings highlight NETs as critical components of anti-<em>G. duodenalis</em> immunity and suggest potential for NETs-targeted therapeutic strategies.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152894"},"PeriodicalIF":2.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hashimoto's Thyroiditis (HT) is a prevalent autoimmune disorder characterized by progressive thyroid damage mediated by T cells. The clonal diversity and expansion of T cells play a critical role in the pathogenesis of HT, but detailed insights into these characteristics at various disease stages are lacking.
Objective
To analyze and compare the clonal diversity and T cell receptor (TCR) repertoire in peripheral blood T cells across different stages of Hashimoto's Thyroiditis using TCR sequencing.
Methods
Peripheral blood samples from 19 HT patients at different disease stages and 4 healthy controls were collected. TCR sequencing was performed to assess T cell diversity and clonal expansion. Statistical analyses, including Shannon's entropy and Simpson's index, were employed to compare TCR diversity. Additionally, differential VJ gene usage and amino acid sequence diversity were analyzed.
Results
The results revealed significant differences in TCR diversity between HT patients and healthy controls, with HT patients showing lower diversity. Notably, the frequency of hyperexpanded clones was higher in HT patients. Specific VJ genes exhibited differential usage patterns across disease stages, and a set of unique amino acid sequences was identified in each stage.
Conclusion
TCR sequencing highlights distinct clonal T cell expansions and shifts in VJ gene usage in HT patients, providing insights into the immune mechanisms driving disease progression.
{"title":"Clonal Analysis of Peripheral Blood T Cells in patients with Hashimoto's Thyroiditis at Different Stages using TCR Sequencing","authors":"Yufeng Liu , Huachao Zhu , Qing Zhang , Yanru Zhao","doi":"10.1016/j.imbio.2025.152890","DOIUrl":"10.1016/j.imbio.2025.152890","url":null,"abstract":"<div><h3>Background</h3><div>Hashimoto's Thyroiditis (HT) is a prevalent autoimmune disorder characterized by progressive thyroid damage mediated by T cells. The clonal diversity and expansion of T cells play a critical role in the pathogenesis of HT, but detailed insights into these characteristics at various disease stages are lacking.</div></div><div><h3>Objective</h3><div>To analyze and compare the clonal diversity and T cell receptor (TCR) repertoire in peripheral blood T cells across different stages of Hashimoto's Thyroiditis using TCR sequencing.</div></div><div><h3>Methods</h3><div>Peripheral blood samples from 19 HT patients at different disease stages and 4 healthy controls were collected. TCR sequencing was performed to assess T cell diversity and clonal expansion. Statistical analyses, including Shannon's entropy and Simpson's index, were employed to compare TCR diversity. Additionally, differential VJ gene usage and amino acid sequence diversity were analyzed.</div></div><div><h3>Results</h3><div>The results revealed significant differences in TCR diversity between HT patients and healthy controls, with HT patients showing lower diversity. Notably, the frequency of hyperexpanded clones was higher in HT patients. Specific VJ genes exhibited differential usage patterns across disease stages, and a set of unique amino acid sequences was identified in each stage.</div></div><div><h3>Conclusion</h3><div>TCR sequencing highlights distinct clonal T cell expansions and shifts in VJ gene usage in HT patients, providing insights into the immune mechanisms driving disease progression.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152890"},"PeriodicalIF":2.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-25DOI: 10.1016/j.imbio.2025.152897
Malika Tami , Lourdes Hontecillas-Prieto , Daniel García-Domínguez , Rocío Flores-Campos , Teresa Vilariño-García , Flora Sánchez-Jiménez , Pilar Guadix , José L. Dueñas , Carlos Jiménez-Cortegana , Luis de la Cruz-Merino , Antonio Pérez-Pérez , Víctor Sánchez-Margalet
Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and significantly increases both maternal and fetal morbidity and mortality. Inflammation is a hallmark of GDM, and placental inflammation may play a key role in the pathophysiology of the disease. Myeloid-derived suppressor cells (MDSCs), which are innate immunosuppressive, are thought to contribute to feto-maternal tolerance. In normal pregnancies, elevated levels of MDSCs have been observed in both peripheral and umbilical cord blood. Our hypothesis postulates that trophoblasts from placentas belonging to women with GDM may have lower levels of MDSCs compared to trophoblasts from placentas originating from healthy pregnancies. Furthermore, since leptin is overexpressed in the placenta of GDM patients, we hypothesized that leptin might contribute to the reduction of MDSCs. To test this, we investigated the in vitro effects of leptin on MDSC levels in isolated peripheral blood leukocytes after 24 h of incubation. Our findings indicate that trophoblasts from placentas from women with GDM contain a lower percentage of MDSCs compared to trophoblasts from healthy pregnancies. In addition, in vitro studies demonstrated that leptin reduces the number of MDSCs in peripheral blood leukocytes.
In conclusion, MDSCs are decreased in placentas from pregnancies with GDM, and leptin appears to reduce the number of MDSCs in leukocytes isolated in vitro. Increased leptin expression in trophoblasts from placentas of women with GDM may contribute to the lower levels of MDSCs, potentially playing a role in placental inflammation. However, further investigations are required to fully elucidate this mechanism.
{"title":"Decreased number of myeloid-derived suppressor cells in the placental trophoblast of gestational diabetes mellitus. Possible role of leptin","authors":"Malika Tami , Lourdes Hontecillas-Prieto , Daniel García-Domínguez , Rocío Flores-Campos , Teresa Vilariño-García , Flora Sánchez-Jiménez , Pilar Guadix , José L. Dueñas , Carlos Jiménez-Cortegana , Luis de la Cruz-Merino , Antonio Pérez-Pérez , Víctor Sánchez-Margalet","doi":"10.1016/j.imbio.2025.152897","DOIUrl":"10.1016/j.imbio.2025.152897","url":null,"abstract":"<div><div>Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and significantly increases both maternal and fetal morbidity and mortality. Inflammation is a hallmark of GDM, and placental inflammation may play a key role in the pathophysiology of the disease. Myeloid-derived suppressor cells (MDSCs), which are innate immunosuppressive, are thought to contribute to feto-maternal tolerance. In normal pregnancies, elevated levels of MDSCs have been observed in both peripheral and umbilical cord blood. Our hypothesis postulates that trophoblasts from placentas belonging to women with GDM may have lower levels of MDSCs compared to trophoblasts from placentas originating from healthy pregnancies. Furthermore, since leptin is overexpressed in the placenta of GDM patients, we hypothesized that leptin might contribute to the reduction of MDSCs. To test this, we investigated the in vitro effects of leptin on MDSC levels in isolated peripheral blood leukocytes after 24 h of incubation. Our findings indicate that trophoblasts from placentas from women with GDM contain a lower percentage of MDSCs compared to trophoblasts from healthy pregnancies. In addition, in vitro studies demonstrated that leptin reduces the number of MDSCs in peripheral blood leukocytes.</div><div>In conclusion, MDSCs are decreased in placentas from pregnancies with GDM, and leptin appears to reduce the number of MDSCs in leukocytes isolated in vitro. Increased leptin expression in trophoblasts from placentas of women with GDM may contribute to the lower levels of MDSCs, potentially playing a role in placental inflammation. However, further investigations are required to fully elucidate this mechanism.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152897"},"PeriodicalIF":2.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-22DOI: 10.1016/j.imbio.2025.152892
Jinguo Wang , Shelley L. Forrest , Sathish Dasari , Hidetomo Tanaka , Ekaterina Rogaeva , M. Carmela Tartaglia , Susan Fox , Anthony E. Lang , Subha Kalyaanamoorthy , Gabor G. Kovacs
Objectives
Progressive supranuclear palsy (PSP) is a neurodegenerative disease showing pathological tau accumulation in subcortical neurons and glial cells. The human leukocyte antigen (HLA) locus on chromosome 6 is a polymorphic region with complex linkage patterns that has been implicated in several autoimmune and neurological disorders. The HLA locus has not been systematically examined in PSP. It is unclear whether tau and HLA can interact to induce an autoimmune disease mechanism.
Methods
We evaluated an autopsy confirmed PSP cohort (n = 44) and compared allele/haplotype frequencies to those of the reference group of a local deceased Canadian donor pool. We performed HLA-Tau peptide binding prediction and modelling of HLA Class II – Tau Peptide interactions.
Findings
Odds ratio was 2.94 (95 % CI 1.01 to 8.55; p = 0.047) for DQB1*06:01 allele, and 2.59 (95 % CI 1.39 to 4.83; p = 0.0025) for the narcolepsy-associated haplotype (DRB1*15:01-DQB1*06:02). One patient with 4-repeat tau PSP-type pathology was a carrier of the IgLON5-associated haplotype (DRB1*10:01-DQB1*05:01). HLA-Tau peptide binding prediction and modelling of HLA Class II – Tau Peptide interactions revealed strong-binding tau peptides but not the PSP-protofilament fold for alleles DQA1*01:02-DQB1*06:02 and DQA1*01:03-DQB1*06:01.
Conclusion
Our study suggests that epitopes within the tau peptide may bind to HLA alleles that are found in a subset of PSP patients supporting the notion of an autoimmune pathophysiological component. These findings have implications for subtyping and stratifying patients for therapies, including those targeting immune modulation.
{"title":"Investigation of the HLA locus in autopsy-confirmed progressive supranuclear palsy","authors":"Jinguo Wang , Shelley L. Forrest , Sathish Dasari , Hidetomo Tanaka , Ekaterina Rogaeva , M. Carmela Tartaglia , Susan Fox , Anthony E. Lang , Subha Kalyaanamoorthy , Gabor G. Kovacs","doi":"10.1016/j.imbio.2025.152892","DOIUrl":"10.1016/j.imbio.2025.152892","url":null,"abstract":"<div><h3>Objectives</h3><div>Progressive supranuclear palsy (PSP) is a neurodegenerative disease showing pathological tau accumulation in subcortical neurons and glial cells. The human leukocyte antigen (<em>HLA</em>) locus on chromosome 6 is a polymorphic region with complex linkage patterns that has been implicated in several autoimmune and neurological disorders. The <em>HLA</em> locus has not been systematically examined in PSP. It is unclear whether tau and HLA can interact to induce an autoimmune disease mechanism.</div></div><div><h3>Methods</h3><div>We evaluated an autopsy confirmed PSP cohort (<em>n</em> = 44) and compared allele/haplotype frequencies to those of the reference group of a local deceased Canadian donor pool. We performed HLA-Tau peptide binding prediction and modelling of HLA Class II – Tau Peptide interactions.</div></div><div><h3>Findings</h3><div>Odds ratio was 2.94 (95 % CI 1.01 to 8.55; <em>p</em> = 0.047) for <em>DQB1</em>*06:01 allele, and 2.59 (95 % CI 1.39 to 4.83; <em>p</em> = 0.0025) for the narcolepsy-associated haplotype (<em>DRB1</em>*15:01-<em>DQB1</em>*06:02). One patient with 4-repeat tau PSP-type pathology was a carrier of the IgLON5-associated haplotype (<em>DRB1</em>*10:01-<em>DQB1</em>*05:01). HLA-Tau peptide binding prediction and modelling of HLA Class II – Tau Peptide interactions revealed strong-binding tau peptides but not the PSP-protofilament fold for alleles DQA1*<em>01:02-DQB1*</em>06:02 and DQA1*<em>01:03-DQB1*</em>06:01.</div></div><div><h3>Conclusion</h3><div>Our study suggests that epitopes within the tau peptide may bind to HLA alleles that are found in a subset of PSP patients supporting the notion of an autoimmune pathophysiological component. These findings have implications for subtyping and stratifying patients for therapies, including those targeting immune modulation.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152892"},"PeriodicalIF":2.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-22DOI: 10.1016/j.imbio.2025.152896
Anwar Ullah, Lina Liu, Xia Qi, Hui Liu
Background
RBC-bound IgG antibody-mediated agglutination occurs when red blood cells (RBCs) cluster together due to the presence of antibodies or other contributing factors. This process could be favorable in the elderly population. Not only is it critical for blood typing procedures, but also plays a significant role in autoimmune hemolytic anemia, a condition characterized by escalated destruction of RBCs. Understanding these mechanisms are essential for precise diagnoses, ensuring the safety of blood transfusions, and facilitating laboratory testing protocols in clinical settings.
Objective
This study explores to detect RBC-bound IgG antibodies in various age groups using flow cytometry method.
Materials and methods
A total of 120 Serum samples were taken from different age groups of healthy individuals. In addation, 30 samples were obtained from individuals with autoimmune diseases, and another 30 samples were collected from healthy elderly individuals of the same ages. Serum (100 μL) were added in eppendorf tube containing equal amount of normal saline and 50 μL of 2 % RBC, mixed well and then kept in water bath at 37 °C for 30 min. After incubation, antihuman globulin (AHG) was added and checked for the index of agglutination (IAG) using flow cytometry method. A control sample was also analyzed using the same method.
Results
Flow cytometry analysis revealed significant differences in IAG between younger individuals and the elderly (P-value 0.003), demonstrating a positive linear relationship. Interestingly, no agglutination was observed in the younger group, whereas elderly healthy individuals exhibited agglutination. Furthermore, significant differences were found between autoimmune disease patients and elderly healthy individuals of the same age groups (P-value 0.0001), with strong IAG in autoimmune patients compared to relatively less agglutination in the elderly population.
Conclusion
Our study has successfully detected RBC-bound IgG antibodies in various age groups. Young age groups showed negative IAG while elderly individuals and patients with autoimmune diseases exhibited the presence of RBC-bound IgG antibodies.
{"title":"A Flow Cytometric Approach to Assess RBC-Bound IgG Antibodies in Different Age Populations","authors":"Anwar Ullah, Lina Liu, Xia Qi, Hui Liu","doi":"10.1016/j.imbio.2025.152896","DOIUrl":"10.1016/j.imbio.2025.152896","url":null,"abstract":"<div><h3>Background</h3><div>RBC-bound IgG antibody-mediated agglutination occurs when red blood cells (RBCs) cluster together due to the presence of antibodies or other contributing factors. This process could be favorable in the elderly population. Not only is it critical for blood typing procedures, but also plays a significant role in autoimmune hemolytic anemia, a condition characterized by escalated destruction of RBCs. Understanding these mechanisms are essential for precise diagnoses, ensuring the safety of blood transfusions, and facilitating laboratory testing protocols in clinical settings.</div></div><div><h3>Objective</h3><div>This study explores to detect RBC-bound IgG antibodies in various age groups using flow cytometry method.</div></div><div><h3>Materials and methods</h3><div>A total of 120 Serum samples were taken from different age groups of healthy individuals. In addation, 30 samples were obtained from individuals with autoimmune diseases, and another 30 samples were collected from healthy elderly individuals of the same ages. Serum (100 μL) were added in eppendorf tube containing equal amount of normal saline and 50 μL of 2 % RBC, mixed well and then kept in water bath at 37 °C for 30 min. After incubation, antihuman globulin (AHG) was added and checked for the index of agglutination (IAG) using flow cytometry method. A control sample was also analyzed using the same method.</div></div><div><h3>Results</h3><div>Flow cytometry analysis revealed significant differences in IAG between younger individuals and the elderly (<em>P</em>-value 0.003), demonstrating a positive linear relationship. Interestingly, no agglutination was observed in the younger group, whereas elderly healthy individuals exhibited agglutination. Furthermore, significant differences were found between autoimmune disease patients and elderly healthy individuals of the same age groups (<em>P</em>-value 0.0001), with strong IAG in autoimmune patients compared to relatively less agglutination in the elderly population.</div></div><div><h3>Conclusion</h3><div>Our study has successfully detected RBC-bound IgG antibodies in various age groups. Young age groups showed negative IAG while elderly individuals and patients with autoimmune diseases exhibited the presence of RBC-bound IgG antibodies.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152896"},"PeriodicalIF":2.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-22DOI: 10.1016/j.imbio.2025.152895
Wei Huang , Weimin Li , Xingyu Chen , Chengwei Xiang , Ke Luo
Background
Tumor-associated macrophages (TAMs) are pivotal in shaping the tumor microenvironment (TME) during cancer progression. Emerging evidence indicates that dysregulation of key signaling pathways in cancer cells drives the secretion of various cytokines, modulating TAMs function. This study aimed to explore how glioblastoma cells regulate macrophages and establish a TME conducive to tumor immune escape.
Methods
In previous bioinformatics studies, we identified abnormally expressed genes in glioblastoma patients. Among them, the metabolism-related protein APOE garnered particular attention. We generated U87 and U251 cell lines with altered APOE expression to evaluate cancer cell invasion, migration, and inflammatory cytokine secretion through scratch assays, Transwell assays, and ELISA, respectively. Additionally, we established a co-culture system of cancer cells and monocytes THP-1 to assess the impact of shAPOE tumor cells on macrophage polarization using flow cytometry, Western blot, and immunofluorescence techniques.
Result
Knockdown of APOE significantly reduced the viability, invasion, and migration capabilities of U87 and U251 cells. ELISA results also showed that APOE knockdown cells secreted higher levels of IL-6, IL-12, and TNF-α, while CCL5 and TGF-β secretion was markedly reduced. In macrophage studies, we observed that APOE knockdown altered the M1/M2 polarization ratio in THP-1 monocytes, with CCR5 inhibition further decreasing M2 macrophage proportions. Immunofluorescence analysis revealed that the reduction of M2 macrophages was dependent on APOE and CCL5.
Conclusion
Our findings indicate that APOE knockdown suppresses glioblastoma cell migration, invasion, and CCL5 secretion, while enhancing the production of tumor-suppressive cytokines.
{"title":"APOE Drives Glioma Progression by Modulating CCL5/CCR5 Signaling in the Tumor Microenvironment and Inducing M2 Macrophage Polarization","authors":"Wei Huang , Weimin Li , Xingyu Chen , Chengwei Xiang , Ke Luo","doi":"10.1016/j.imbio.2025.152895","DOIUrl":"10.1016/j.imbio.2025.152895","url":null,"abstract":"<div><h3>Background</h3><div>Tumor-associated macrophages (TAMs) are pivotal in shaping the tumor microenvironment (TME) during cancer progression. Emerging evidence indicates that dysregulation of key signaling pathways in cancer cells drives the secretion of various cytokines, modulating TAMs function. This study aimed to explore how glioblastoma cells regulate macrophages and establish a TME conducive to tumor immune escape.</div></div><div><h3>Methods</h3><div>In previous bioinformatics studies, we identified abnormally expressed genes in glioblastoma patients. Among them, the metabolism-related protein APOE garnered particular attention. We generated U87 and U251 cell lines with altered APOE expression to evaluate cancer cell invasion, migration, and inflammatory cytokine secretion through scratch assays, Transwell assays, and ELISA, respectively. Additionally, we established a co-culture system of cancer cells and monocytes THP-1 to assess the impact of shAPOE tumor cells on macrophage polarization using flow cytometry, Western blot, and immunofluorescence techniques.</div></div><div><h3>Result</h3><div>Knockdown of APOE significantly reduced the viability, invasion, and migration capabilities of U87 and U251 cells. ELISA results also showed that APOE knockdown cells secreted higher levels of IL-6, IL-12, and TNF-α, while CCL5 and TGF-β secretion was markedly reduced. In macrophage studies, we observed that APOE knockdown altered the M1/M2 polarization ratio in THP-1 monocytes, with CCR5 inhibition further decreasing M2 macrophage proportions. Immunofluorescence analysis revealed that the reduction of M2 macrophages was dependent on APOE and CCL5.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that APOE knockdown suppresses glioblastoma cell migration, invasion, and CCL5 secretion, while enhancing the production of tumor-suppressive cytokines.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152895"},"PeriodicalIF":2.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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