Immunologic Research最新文献

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The role of dendritic cells in recurrent pregnancy loss. 树突状细胞在复发性妊娠丢失中的作用。
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-07-21 DOI: 10.1007/s12026-025-09664-z
Xingxing Yuan, Chaofan Li, Liuxin Yang, Xiaoyu Zhang, Xiaoling Feng
{"title":"The role of dendritic cells in recurrent pregnancy loss.","authors":"Xingxing Yuan, Chaofan Li, Liuxin Yang, Xiaoyu Zhang, Xiaoling Feng","doi":"10.1007/s12026-025-09664-z","DOIUrl":"https://doi.org/10.1007/s12026-025-09664-z","url":null,"abstract":"<p><p>Recurrent pregnancy loss (RPL), defined as ≥ 2 consecutive losses, remains a significant clinical challenge with complex immunological underpinnings. While immune dysfunction underpins RPL, dendritic cells (DCs) emerge as central regulators of maternal-fetal tolerance. This review comprehensively explores the multifaceted roles of DC subsets at the maternal-fetal interface, including their contribution to immune tolerance, angiogenesis, placental development, and bidirectional interactions with trophoblasts and natural killer (NK) cells. We detail specific DC alterations in RPL, encompassing phenotypic shifts, functional defects, and disrupted DC-NK cell crosstalk, linking these changes to pregnancy loss risk. Emerging evidence highlights therapeutic strategies targeting DCs, such as tolerogenic DC vaccines and interventions modulating trophoblast MHC antigen presentation, alongside established immunomodulation, to restore immune balance. Underlying mechanisms like systemic inflammation impacting endometrial DCs are also discussed. By synthesizing current literature and controversies, this review elucidates the critical, yet complex, role of DC heterogeneity and function in RPL pathogenesis and discusses innovative interventions aimed at improving pregnancy outcomes.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"108"},"PeriodicalIF":3.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674669","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 impact of neddylation on prognosis in the immune microenvironment of neuroblastoma: a single-cell transcriptomic analysis. 类化修饰对神经母细胞瘤免疫微环境预后的影响:单细胞转录组学分析。
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-07-17 DOI: 10.1007/s12026-025-09662-1
Juan You, Hu Yang
{"title":"The impact of neddylation on prognosis in the immune microenvironment of neuroblastoma: a single-cell transcriptomic analysis.","authors":"Juan You, Hu Yang","doi":"10.1007/s12026-025-09662-1","DOIUrl":"https://doi.org/10.1007/s12026-025-09662-1","url":null,"abstract":"<p><p>Neuroblastoma (NB) is a prevalent malignant tumor in children, primarily affecting the nervous system, with a high mortality rate, particularly in high-risk patients. This study aims to establish a neddylation-related prognostic signature (NRPS) through the analysis of gene expression data from NB patients and to evaluate its clinical application potential. A comprehensive analysis was conducted using gene expression profiling, single-cell RNA sequencing (scRNA-seq), weighted gene co-expression network analysis (WGCNA), and single-sample gene set enrichment analysis (ssGSEA) to elucidate the role of neddylation and establish a NRPS for NB patients. Our analysis identified 171,992 cells categorized into 19 distinct clusters, revealing that Schwann and tumor cells exhibited significantly higher neddylation scores compared to other cell types. We constructed a NRPS that significantly impacts overall survival and event-free survival. Immune infiltration analysis demonstrated significantly higher levels of immune cells, particularly activated CD8 + T cells and natural killer cells, in the low-risk group, indicating a stronger anti-tumor immune response. Furthermore, gene set enrichment analysis (GSEA) revealed that the high-risk group was associated with cell division and DNA repair pathways, while the low-risk group showed enrichment in immune-related signaling pathways, suggesting immune activation may confer protective effects. Additionally, the immunotherapy analysis suggested that the low-risk score group exhibited better immunotherapy outcomes. This study underscores the clinical significance of NRPS in predicting survival and therapeutic outcomes in NB patients, highlighting their necessity and urgency in personalized treatment approaches.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"107"},"PeriodicalIF":3.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659119","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
Metabolic-associated enthesitis: a review on pathophysiology, clinical relevance, diagnostic challenges, and perspective on target treatments. 代谢性阑尾炎:病理生理学,临床相关性,诊断挑战和靶向治疗的观点综述。
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-07-11 DOI: 10.1007/s12026-025-09655-0
Giuseppe Lisco, Anna De Tullio, Roberta Zupo, Marcella Prete, Giuseppina Piazzolla, Vito Racanelli, Vincenzo Triggiani
{"title":"Metabolic-associated enthesitis: a review on pathophysiology, clinical relevance, diagnostic challenges, and perspective on target treatments.","authors":"Giuseppe Lisco, Anna De Tullio, Roberta Zupo, Marcella Prete, Giuseppina Piazzolla, Vito Racanelli, Vincenzo Triggiani","doi":"10.1007/s12026-025-09655-0","DOIUrl":"https://doi.org/10.1007/s12026-025-09655-0","url":null,"abstract":"<p><p>Entheses are specialized tissues that connect ligaments and tendons to the bone surface and are frequently involved in seronegative spondyloarthritis. Enthesitis can also be detected in patients with metabolic disorders (MD), regardless of baseline autoimmune rheumatic disease, posing real diagnostic challenges. The present review discusses the pathophysiology of enthesitis and metabolic-associated enthesitis, the clinical relevance of metabolic disorders on enthesitis-related outcomes, diagnostic challenges for adequate differential diagnosis, and possible therapeutic strategies to improve clinical outcomes. PubMed/MEDLINE and the Cochrane Library were searched for original articles, systematic reviews, and meta-analyses. References were screened according to a hierarchical analysis of studies by title, abstract, and full text, collected, presented, and discussed. Metabolic-associated enthesitis is attributable to mechanical stress/overload due to weight excess typically observed in metabolic disorders (MD), such as overweight/obese comorbid patients, metabolic syndrome (MS), and type 2 diabetes (T2D). Interleukin 1β, 6, 17, 18, and 23 and tumor necrosis factor-α play a crucial role in initiating and maintaining entheseal inflammation. Chronic hyperglycemia and insulin resistance lead to a vicious circle as they stimulate, upon activated, specialized T cells to produce these specific cytokines, thus maintaining entheseal inflammation chronically. MD is associated with more severe clinical presentation, worse response to pharmacological treatments, and poor entheseal outcomes also in patients with existing seronegative spondyloarthritis. Non-immune-mediated metabolic-associated enthesitis poses a real diagnostic challenge, possibly underestimating cases and potential misdiagnoses. From a therapeutic viewpoint, glucose control improvement and weight loss are associated with relevant amelioration of entheseal-related outcomes. Pharmacological and non-pharmacological interventions aiming to reduce body weight, improve glucose control and insulin sensitivity, and attenuate inflammation are desirable to achieve the therapeutic target. Glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter type 2 inhibitors, in add-on to non-steroidal anti-inflammatory drugs and immunomodulators when necessary, may have a therapeutic rationale in patients with metabolic-associated enthesitis. Awareness of metabolic-associated enthesitis is essential to improve the accuracy of differential diagnosis in patients with MD and prescribe appropriate therapeutic strategies. However, basic and clinical research is needed to understand the role of \"antihyperglycemic\" agents in better managing metabolic-associated enthesitis.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"106"},"PeriodicalIF":3.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144617405","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
Dysautonomia: a common comorbidity of systemic disease. 自主神经异常:全身性疾病的常见合并症。
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-07-08 DOI: 10.1007/s12026-025-09661-2
Svetlana Blitshteyn
{"title":"Dysautonomia: a common comorbidity of systemic disease.","authors":"Svetlana Blitshteyn","doi":"10.1007/s12026-025-09661-2","DOIUrl":"10.1007/s12026-025-09661-2","url":null,"abstract":"<p><p>Referring to a broad spectrum of the autonomic symptoms, autonomic disorders, and general dysfunction of the autonomic nervous system, dysautonomia is one of the common and under-recognized comorbidities of a wide variety of systemic disease, including diabetes, autoimmune disorders, vitamin deficiencies, and hormonal dysregulation. The most common autonomic disorders encountered in clinical practice are postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope (NCS), and orthostatic hypotension (OH), which may be undiagnosed or often mislabeled with psychiatric disorders. Typical clinical features of dysautonomia, such as orthostatic dizziness/lightheadedness, orthostatic intolerance, palpitations, exercise intolerance, cognitive dysfunction, and fatigue, should prompt a diagnostic investigation for dysautonomia, which includes an in-office 10-min stand test or a tilt table test in conjunction with other autonomic function tests if available. Treatment approach consists of non-pharmacologic and pharmacologic therapies with beta blockers, midodrine, ivabradine, pyridostigmine, fludrocortisone, stimulants, and other medications. In clinical setting, dysautonomia may present a diagnostic and therapeutic challenge in patients with various systemic disorders and may require a high index of suspicion on the part of the clinician. Importantly, diagnosing and treating dysautonomia is critical to providing comprehensive and personalized medical care to complex patients with chronic illness, who are typically highly symptomatic with multi-systemic complaints as a result of comorbid, and often undiagnosed, dysautonomia.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"105"},"PeriodicalIF":3.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583818","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}
引用次数: 0
Immunological and clinical characteristics in a cohort of Colombian pediatric patients with 22q11.2 deletion. 22q11.2缺失哥伦比亚儿童患者队列的免疫学和临床特征
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-07-05 DOI: 10.1007/s12026-025-09660-3
Lina M Castano-Jaramillo, Roy Sanguino-Lobo, Silvia Maradei, Natalia Velez-Tirado
{"title":"Immunological and clinical characteristics in a cohort of Colombian pediatric patients with 22q11.2 deletion.","authors":"Lina M Castano-Jaramillo, Roy Sanguino-Lobo, Silvia Maradei, Natalia Velez-Tirado","doi":"10.1007/s12026-025-09660-3","DOIUrl":"https://doi.org/10.1007/s12026-025-09660-3","url":null,"abstract":"<p><p>22q11.2 deletion syndrome (22qDS) is a heterogeneous genetic disorder associated with a variety of clinical manifestations, including congenital heart disease, neuropsychiatric disorders, hypocalcemia, and immunological deficiencies. This study aimed to characterize the clinical and immunological features of patients with 22qDS in a cohort from Colombia. We conducted a retrospective study over a 3-year period, including 40 patients with confirmed 22qDS. Demographic, clinical, and immunological data were collected from medical records. The cohort had a median age of 3 years, with a balanced sex distribution. Heart defects were present in 75% of patients, followed by ear and craniofacial abnormalities (50%) and language disorders (45%). Immunological work-up revealed low T cell subsets in 42% of patients, with a decrease in T cell lymphopenia observed with age. Humoral deficiencies were also common, with 20% of patients exhibiting selective IgM deficiency and 17% presenting with hypogammaglobulinemia. Recurrent infections were observed in 48% of patients, particularly pneumonia and otitis. Vaccine responses to protein-based antigens and polysaccharides were frequently impaired. The findings highlight the clinical and immunological heterogeneity of 22qDS in this Latin American cohort. Multidisciplinary care, early diagnosis, and immunological management are essential for improving outcomes in these patients.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"104"},"PeriodicalIF":3.3,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564751","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
Risk factors for infections in systemic lupus erythematosus: a meta-analysis. 系统性红斑狼疮感染的危险因素:荟萃分析。
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-07-04 DOI: 10.1007/s12026-025-09651-4
Yanan Xuan, Jin Wang, Yi Yuan, Xiaofeng Zhao, Fangfang Zuo, Shuangshuang Liu, Lijuan Wan
{"title":"Risk factors for infections in systemic lupus erythematosus: a meta-analysis.","authors":"Yanan Xuan, Jin Wang, Yi Yuan, Xiaofeng Zhao, Fangfang Zuo, Shuangshuang Liu, Lijuan Wan","doi":"10.1007/s12026-025-09651-4","DOIUrl":"10.1007/s12026-025-09651-4","url":null,"abstract":"<p><p>Immune dysfunction in patients with systemic lupus erythematosus (SLE) increases susceptibility to infections, complicating their management. Identifying risk factors for infections is essential for improving clinical outcomes. A meta-analysis was conducted to evaluate factors associated with infection risk in patients with SLE. Relevant studies were retrieved from PubMed, Web of Science, Embase, and Scopus databases from inception to November 2023. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using R software (version 4.3.1). Factors analyzed included age, gender, active disease stage, diabetes mellitus, kidney injury, hydroxychloroquine, high-dose glucocorticoids, immunosuppressive drugs, lymphopenia, anti-dsDNA, and complement 3 (C3). Twenty-one studies were included. The analysis identified several factors significantly associated with increased infection risk: age (OR = 1.02, 95% CI 1.01-1.04), being male (OR = 1.66, 95% CI 1.19-2.33), active disease stage (OR = 1.74, 95% CI 1.25-2.43), diabetes mellitus (OR = 1.64, 95% CI 0.92-2.93), kidney injury (OR = 1.78, 95% CI 1.37-2.30), high-dose glucocorticoids (OR = 2.40, 95% CI 1.88-3.80), immunosuppressive drugs (OR = 2.24, 95% CI 1.15-4.38), lymphopenia (OR = 3.59, 95% CI 2.42-5.33), and low C3 (OR = 2.38, 95% CI 1.13-5.03). Older age, male gender, active disease, diabetes, kidney injury, high-dose glucocorticoid use, immunosuppressants, lymphopenia, and decreased C3 levels may increase the risk of infections in SLE. These findings highlight the importance of individualized infection prevention strategies in high-risk patients.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"103"},"PeriodicalIF":3.3,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560037","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 activities of carbon quantum dots on the primary macrophages and whole splenocytes. 碳量子点对原代巨噬细胞和全脾细胞的免疫调节作用。
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-06-28 DOI: 10.1007/s12026-025-09652-3
Furkan Ayaz, Basak Kavrak, Besa Bilakaya, Gamze Çamlik, Fatma Sude Özarslan, İsmail Tuncer Değim
{"title":"Immunomodulatory activities of carbon quantum dots on the primary macrophages and whole splenocytes.","authors":"Furkan Ayaz, Basak Kavrak, Besa Bilakaya, Gamze Çamlik, Fatma Sude Özarslan, İsmail Tuncer Değim","doi":"10.1007/s12026-025-09652-3","DOIUrl":"https://doi.org/10.1007/s12026-025-09652-3","url":null,"abstract":"<p><p>Quantum dots, because of some of their fascinating features, like continuous radiation emission, crossing the biological barrier, and potential for drug carrying, have emerged as versatile nanomaterials in enormous applications relating to drug development and health sciences. Among such quantum dots, carbon quantum dots have gained widespread attention due to their low toxicity, high biocompatibility, and excellent photostability. The present work investigates the immunomodulatory properties of CQDs with diverse chemical characteristics against primary macrophages and whole splenocytes. Since macrophages are important regulators of immune responses, their isolation and activation by toll-like receptor agonists were performed to evaluate the production of pro-inflammatory cytokines and intracellular signaling pathways. Our data indicate that different CQD formulations possess specific immunomodulatory activities, while some of them reveal adjuvant capabilities; others act anti-inflammatory. Importantly, the zinc-containing CQDs enhance pro-inflammatory responses, which may find applications as vaccine adjuvants. These findings highlight the therapeutic possibilities of CQDs in the treatment of inflammatory diseases and enhancement of vaccine efficacy.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"102"},"PeriodicalIF":3.3,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527755","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 epidemiological trends of inflammatory bowel disease among women of reproductive age: a global analysis from 1990 to 2021. 育龄妇女炎症性肠病流行病学趋势:1990年至2021年的全球分析
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-06-27 DOI: 10.1007/s12026-025-09658-x
Zhenzhen Fan, He Zhou, Lianlian Tian, Tong Wu, JiaQi Zhang, Junchao Lin, Chen Wang, Jindan He, LiuQing Zhao, Jie Chen, Jie Liang
{"title":"The epidemiological trends of inflammatory bowel disease among women of reproductive age: a global analysis from 1990 to 2021.","authors":"Zhenzhen Fan, He Zhou, Lianlian Tian, Tong Wu, JiaQi Zhang, Junchao Lin, Chen Wang, Jindan He, LiuQing Zhao, Jie Chen, Jie Liang","doi":"10.1007/s12026-025-09658-x","DOIUrl":"https://doi.org/10.1007/s12026-025-09658-x","url":null,"abstract":"<p><p>This study aimed to evaluate the global burden of inflammatory bowel disease (IBD) among women of reproductive age (15-49 years) from 1990 to 2021, analyze its association with socio-demographic index (SDI), and identify age-period-cohort (APC) effects to inform region-specific public health strategies. Using data from the Global Burden of Disease (GBD) 2021 study, we assessed age-standardized incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (ASDR) across 204 countries. Statistical analyses included Pearson correlation to evaluate SDI associations, decomposition analysis to quantify burden drivers, and APC modeling to disentangle age, period, and cohort effects. In 2021, the global ASIR, ASPR, ASMR, and ASDR for IBD in women of reproductive age were 4.38, 45.90, 0.50, and 17.75 per 100,000, respectively. The health burden of IBD in women of reproductive age varies by region. Australasia has the highest ASIR and ASPR globally, while these metrics are lowest in Central Latin America. Western Europe exhibits the highest ASMR, whereas Oceania has the lowest. In terms of ASDR North America, with its higher income, bears the heaviest burden, while Oceania experiences the lightest. Furthermore, APC analysis revealed age-specific risks peaking at 45-49 years, and significant cohort effects in middle/low-SDI regions, where post-1977 birth cohorts showed elevated incidence. Period effects highlighted diverging trends: stable incidence in high-SDI regions vs. rising rates in mid-SDI regions due to urbanization and lifestyle shifts. The IBD burden among reproductive-aged women is rising disproportionately, shaped by SDI gradients and demographic transitions. High-SDI regions require strategies targeting aging populations and comorbidities, while low/middle-SDI regions need investments in early diagnosis and equitable care.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"101"},"PeriodicalIF":3.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505572","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
HBV infection upregulates GP73 expression to promote liver fibrosis by enhancing ER stress via the Smad2 pathway. HBV感染通过Smad2途径增强内质网应激,上调GP73表达,促进肝纤维化。
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-06-27 DOI: 10.1007/s12026-025-09656-z
Ying He, Lianying Cai, Liu Liu, Yuxu Zhang, Lu Si, Qiuchen Cheng, Shuangyan Luo
{"title":"HBV infection upregulates GP73 expression to promote liver fibrosis by enhancing ER stress via the Smad2 pathway.","authors":"Ying He, Lianying Cai, Liu Liu, Yuxu Zhang, Lu Si, Qiuchen Cheng, Shuangyan Luo","doi":"10.1007/s12026-025-09656-z","DOIUrl":"https://doi.org/10.1007/s12026-025-09656-z","url":null,"abstract":"<p><p>Endoplasmic reticulum (ER) stress induced by hepatitis B virus (HBV) infection is associated with the development of liver fibrosis. Golgi protein 73 (GP73) is increased during HBV infection. Nevertheless, whether GP73 during HBV infection mediates ER stress in liver fibrosis is still poorly understood. TGF-β1 was used to induce HepG2.2.15 cells to establish liver fibrosis cells model. GP73 expression was evaluated using qRT-PCR analysis and Western blot. HepG2.2.15 cells viability and proliferation were assessed via CCK-8 assay and EdU assay, respectively. The protein levels of α-SMA, fibronectin, collagen I and collagen III for liver fibrosis, GRP78, p-PERK, p-eIF2α, ATF4 and CHOP for ER stress, as well as p-Smad2 and Smad2 were evaluated by Western blot. TGF-β1 incubation obviously elevated GP73 expression, while GP73 knockdown reduced the GP73 levels in HBV-transfected HepG2215 cells. GP73 knockdown reversed the effects of TGF-β1 exposure on HepG2.2.15 cells viability and proliferation. The protein levels of liver fibrosis marker, ERS marker and p-Smad2 were remarkably increased following TGF-β1 stimulation, which were counteracted by GP73 silence or the application of 4-phenylbutyric acid (4-PBA). However, these results were opposite after tunicamycin (TM) treatment. In conclusion, knockdown of GP73 potentially impeded the advancement of liver fibrosis via mediating ERs through Smad2 signal pathway.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"100"},"PeriodicalIF":3.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505570","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 activity of 4-(Benzyloxy)phenol facilitates intracellular mycobacterial clearance through p53 mediated IL-35 signaling dependent JAK1/STAT3 pathway in human macrophages. 在人巨噬细胞中,4-(苯氧基)酚的免疫调节活性通过p53介导的IL-35信号依赖性JAK1/STAT3途径促进细胞内分枝杆菌的清除。
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-06-26 DOI: 10.1007/s12026-025-09657-y
Lincoln Naik, Salina Patel, Mousumi Das, Dev Kiran Nayak, Pramathesh Kumar Dandsena, Mustafeez Ali Quaderi, Ashish Kumar, Amit Mishra, Ramandeep Singh, Abtar Mishra, Rohan Dhiman
{"title":"Immunomodulatory activity of 4-(Benzyloxy)phenol facilitates intracellular mycobacterial clearance through p53 mediated IL-35 signaling dependent JAK1/STAT3 pathway in human macrophages.","authors":"Lincoln Naik, Salina Patel, Mousumi Das, Dev Kiran Nayak, Pramathesh Kumar Dandsena, Mustafeez Ali Quaderi, Ashish Kumar, Amit Mishra, Ramandeep Singh, Abtar Mishra, Rohan Dhiman","doi":"10.1007/s12026-025-09657-y","DOIUrl":"https://doi.org/10.1007/s12026-025-09657-y","url":null,"abstract":"<p><p>Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis (TB), modulates host immune responses by regulating various cytokines. Precise regulation of these cytokines renders the host pathogen-free, whereas their dysregulation increases the susceptibility to infection. Hence, induction of host protective cytokines using immunomodulators to promote M. tuberculosis clearance has a rewarding impact in the context of TB treatment. This study explored the immunomodulatory activity of 4-(Benzyloxy)phenol (4-BOP) in mycobacteria infected differentiated THP-1 cells through IL-35 (an anti-inflammatory cytokine) production. Initially, we observed an increased mRNA and protein level expression of IL-35 and its cognate receptor upon 4-BOP treatment in mycobacteria-infected dTHP-1 cells. IL-35 receptor activation further led to phosphorylation of JAK1/STAT3, culminating in increased phagosome-lysosome fusion through elevation of intracellular Ca<sup>2+</sup> level. Blocking IL-35 receptors using siRNA-mediated approach against IL-12Rβ2 and gp130 or the JAK1/STAT3 associated signaling with specific inhibitors like Baricitinib and Stattic promoted the intracellular mycobacterial survival by compromising Ca<sup>2+</sup>-phagosome-lysosome fusion pathway. Further, we identified a direct regulatory role of p53 (known to be activated by 4-BOP) on IL-35 production, and inhibition of p53 using PFT-α surprisingly abrogated the IL-35 mediated signaling axis. Collectively, our results demonstrated a host defensive role of 4-BOP-induced Il-35 signaling in mycobacteria-infected dTHP-1 cells through the JAK1/STAT3 mediated Ca<sup>2+</sup>-phagosome-lysosome fusion pathway. These results suggest that 4-BOP may serve as a potent HDT candidate for regulating inflammation and enhancing host defense in TB infection.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"99"},"PeriodicalIF":3.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505571","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
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