Frontiers in Immunology最新文献

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Targeting senescent microglia in progressive multiple sclerosis: a geroscience-informed approach. 靶向衰老小胶质细胞在进展性多发性硬化症:一个老年科学知情的方法。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-10-07 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1681724
Jeffrey Atkinson, Amy Dokiburra, Hayley Groover, Jonathan P Godbout, Benjamin M Segal, Yinan Zhang
{"title":"Targeting senescent microglia in progressive multiple sclerosis: a geroscience-informed approach.","authors":"Jeffrey Atkinson, Amy Dokiburra, Hayley Groover, Jonathan P Godbout, Benjamin M Segal, Yinan Zhang","doi":"10.3389/fimmu.2025.1681724","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1681724","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disorder of the central nervous system (CNS). Age is the strongest predictor of disease phenotype, with the majority of older adults transitioning to a progressive form marked by irreversible neurological decline. This clinical progression is associated with smoldering, CNS-compartmentalized inflammation and neurodegeneration, for which there are currently no effective disease-modifying therapies. Cellular senescence, characterized by the secretion of pro-inflammatory mediators collectively known as the senescence-associated secretory phenotype (SASP), increases with age and contributes to tissue injury. In MS, neuroinflammation can further promote cellular senescence, creating a self-reinforcing cycle of damage. Senescent microglia have been identified within MS lesions, where their SASP may impair remyelination and exacerbate neurodegeneration. Senolytic agents selectively target and eliminate senescent cells by disrupting anti-apoptotic pathways. In experimental autoimmune encephalomyelitis (EAE), a widely used model of MS, senolytic treatment reduces senescent microglia burden and attenuates disease severity in an age- and drug-dependent manner. Specifically, here we show that middle-aged mice (40-44 weeks) with EAE exhibit improved clinical outcomes and survival following treatment with either dasatinib plus quercetin (D+Q) or navitoclax. Early-phase clinical trials of senolytics in age-related diseases have demonstrated functional benefits, including improved gait speed in idiopathic pulmonary fibrosis and CNS penetrance in Alzheimer's disease. Translating senolytic therapy to MS will require careful selection of CNS-penetrant and well-tolerated agents, identification of appropriate patient populations, and deployment of responsive biomarkers. Senolytic therapy represents a promising geroscience-based strategy to meet the urgent therapeutic need in progressive MS.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1681724"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Secondary antibody deficiencies in the modern era: emerging trends, diagnostic pitfalls, and advances in personalised management. 二抗缺陷在现代时代:新趋势,诊断陷阱,和进步的个性化管理。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-10-07 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1635094
Shuayb Elkhalifa, Fulvio Salvo, Haggar Elbashir, Irfan Shafiq, Saed Isse, Mohamed Abuzakouk, Mohamed Medhat Gaber, Rehan Bhana
{"title":"Secondary antibody deficiencies in the modern era: emerging trends, diagnostic pitfalls, and advances in personalised management.","authors":"Shuayb Elkhalifa, Fulvio Salvo, Haggar Elbashir, Irfan Shafiq, Saed Isse, Mohamed Abuzakouk, Mohamed Medhat Gaber, Rehan Bhana","doi":"10.3389/fimmu.2025.1635094","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1635094","url":null,"abstract":"<p><p>Secondary antibody deficiencies (SADs) are a significant but frequently under-recognised group of acquired immunodeficiencies. They may arise in various clinical settings, including haematological malignancies, immunosuppressive therapies, and protein-losing conditions. SADs are associated with an increased risk of recurrent and severe infections, hospitalisation, and impaired quality of life. Despite this, diagnostic and treatment pathways remain inconsistent across healthcare settings and regions. Recent advances in the use of structured clinical data, including electronic health records and systematic laboratory assessments, show promise in facilitating earlier recognition of SADs. These approaches support more timely treatment decisions and promote consistent standards of care. Achieving improved outcomes for individuals with SADs will require broader consensus on diagnostic criteria, treatment thresholds, and access to specialist immunology services.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1635094"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Nomogram for predicting postoperative recurrence in patients with microvascular invasion-negative hepatocellular carcinoma: development and validation. 预测微血管浸润阴性肝细胞癌患者术后复发的Nomogram:发展与验证。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-10-07 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1614392
Qingwang Ye, Yi Yu, Shujie Pang, Dongbo Zhao, Dongqian Li, Yao Ma, Ning Yang, Wei Feng
{"title":"Nomogram for predicting postoperative recurrence in patients with microvascular invasion-negative hepatocellular carcinoma: development and validation.","authors":"Qingwang Ye, Yi Yu, Shujie Pang, Dongbo Zhao, Dongqian Li, Yao Ma, Ning Yang, Wei Feng","doi":"10.3389/fimmu.2025.1614392","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1614392","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) imposes a substantial global health burden, while postoperative recurrence remains a pivotal factor contributing to poor prognosis. Although existing prognostic models predominantly focus on patients with HCC with microvascular invasion (MVI), recurrence mechanisms and risk stratification in those with MVI-negative HCC remain underexplored despite their distinct clinicopathological profiles. As such, this study aimed to develop a prognostic nomogram to predict recurrence-free survival (RFS) in patients with MVI-negative HCC.</p><p><strong>Methods: </strong>Data from 547 treatment-naïve patients with MVI-negative HCC were divided into 2 cohorts: training (n=375); and external validation (n=172). Random survival forest and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram prediction model was developed based on risk factors identified in the training cohort and subsequently validated in the external validation cohort.</p><p><strong>Results: </strong>Key findings revealed that Ki-67, alpha-fetoprotein (AFP)-L3, neutrophil-to-lymphocyte ratio, AFP, and systemic immune-inflammation index significantly impacted RFS, with a concordance-index (C-index) exceeding 0.7 for the nomogram model in the training cohort, and an area under the receiver operating characteristic curve (AUC) of 0.758, 0.769, and 0.779 for 1-, 3-, and 5-year RFS, respectively. The external validation cohort corroborated these findings, achieving C-index values > 0.7 and AUC values of 0.717, 0.735, and 0.756 for the same time points. The calibration curves indicated strong agreement between the predicted and actual outcomes. Decision curve analysis revealed that the nomogram model demonstrated good net benefits for 1-, 3-, and 5-year RFS in both the training and external validation cohorts.</p><p><strong>Conclusion: </strong>This study developed and validated a prognostic nomogram for predicting postoperative disease recurrence in patients with MVI-negative HCC, highlighting the importance of individualized patient management based on the risk factors identified.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1614392"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Commentary: PSD3 as a context-dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinoma. 评论:PSD3在食管鳞状细胞癌中作为免疫景观和肿瘤侵袭性的环境依赖调节剂。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-10-07 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1687140
Dongdong Zhang, Pei Zhang, Ran Jing, Ziwei Chen, Ming Cai
{"title":"Commentary: PSD3 as a context-dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinoma.","authors":"Dongdong Zhang, Pei Zhang, Ran Jing, Ziwei Chen, Ming Cai","doi":"10.3389/fimmu.2025.1687140","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1687140","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1687140"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Eosinophils as predictive biomarkers in anti-programmed cell death 1 monotherapy for non-small cell lung cancer. 嗜酸性粒细胞作为非小细胞肺癌抗程序性细胞死亡1单药治疗的预测性生物标志物
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-10-07 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1574314
Takahiro Uchida, Kazuyuki Nakagome, Kosuke Hashimoto, Hidetoshi Iemura, Yuki Shiko, Atsuto Mouri, Ou Yamaguchi, Yoshitaka Uchida, Yoshiaki Nagai, Tomoyuki Soma, Kyoichi Kaira, Makoto Nagata, Hiroshi Kagamu
{"title":"Eosinophils as predictive biomarkers in anti-programmed cell death 1 monotherapy for non-small cell lung cancer.","authors":"Takahiro Uchida, Kazuyuki Nakagome, Kosuke Hashimoto, Hidetoshi Iemura, Yuki Shiko, Atsuto Mouri, Ou Yamaguchi, Yoshitaka Uchida, Yoshiaki Nagai, Tomoyuki Soma, Kyoichi Kaira, Makoto Nagata, Hiroshi Kagamu","doi":"10.3389/fimmu.2025.1574314","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1574314","url":null,"abstract":"<p><strong>Background: </strong>The relationship between eosinophilia and cancer development has recently been investigated. However, the role of eosinophils in tumor immunity, particularly in the context of immune checkpoint inhibitor (ICI) therapy, remains poorly understood.</p><p><strong>Methods: </strong>We investigated the relationship between peripheral blood eosinophil and T-lymphocyte subsets and the clinical characteristics of patients undergoing anti-programmed cell death-1 (PD-1) monotherapy for non-small cell lung cancer (NSCLC). The study included 204 patients treated with nivolumab monotherapy, and clinical data and treatment responses were recorded. PBMCs were collected from 44 out of 204 patients before treatment to analyze T-lymphocyte subsets, focusing on their correlation with blood eosinophils.</p><p><strong>Results: </strong>The percentage of blood eosinophils before nivolumab treatment was positively correlated with the percentage of effector memory subsets in both CD4<sup>+</sup> (r = 0.43, p = 0.0045) and CD8<sup>+</sup> T cells (r = 0.35, p = 0.020). It was negatively correlated with the percentage of naïve subsets of CD4<sup>+</sup> T cells and positively correlated with the percentage of inducible T cell co-stimulator cells among CD8<sup>+</sup> T cells. Patients with higher eosinophil levels (≥1.7%) before nivolumab treatment exhibited significantly longer progression-free survival (log-rank p = 0.014) and overall survival (log-rank p = 0.001) than those with lower eosinophil levels. An early increase in the eosinophil count after treatment was also associated with a better response to nivolumab.</p><p><strong>Conclusion: </strong>Higher blood eosinophil levels may indicate activated T-cell immunity and may be a promising biomarker for the efficacy of anti-PD-1 monotherapy in patients with NSCLC.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1574314"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Deciphering macrophage differentiation and cell death dynamics in heart failure: a single-cell sequencing odyssey. 心力衰竭中巨噬细胞分化和细胞死亡动力学的解读:单细胞测序奥德赛。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-10-07 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1604226
Jin Wei, Yao Sun, Bao-Xi Qu, Xin-Xin Duan, Li-Hong Yan, Wei An, Kun-Lun Yin, Shui-Yun Wang, Yan-Hai Meng, Lei Huang
{"title":"Deciphering macrophage differentiation and cell death dynamics in heart failure: a single-cell sequencing odyssey.","authors":"Jin Wei, Yao Sun, Bao-Xi Qu, Xin-Xin Duan, Li-Hong Yan, Wei An, Kun-Lun Yin, Shui-Yun Wang, Yan-Hai Meng, Lei Huang","doi":"10.3389/fimmu.2025.1604226","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1604226","url":null,"abstract":"<p><strong>Aims: </strong>We hypothesize that specific macrophage differentiation trajectories in heart failure (HF) are coupled with subtype-specific and context-dependent engagement of programmed cell death (PCD) pathways, particularly ferroptosis and anoikis, which in turn influence disease progression and remodeling. HF is a progressive and heterogeneous clinical syndrome characterized by adverse immune remodeling, yet the precise contributions of macrophage heterogeneity, lineage dynamics, and PCD programs to its pathogenesis remain unclear. This study aimed to delineate, at single-cell resolution, the cellular and molecular landscape of cardiac macrophage subpopulations and their engagement with immunogenic cell death programs.</p><p><strong>Methods: </strong>We profiled human cardiac tissues from HF and non-failing donors using scRNA-seq from the SCP1303 dataset, initially comprising ~600,000 cells and reduced to ~120,000 high-quality cells from 18 samples after stringent quality control to retain biologically valid but metabolically distinct populations. Standardized cell-type annotation and pseudotime trajectory reconstruction were applied. Pathway activity was quantified using AUCell (primary) and GSVA (complementary) for cell death-related signatures. Integrated differential expression analysis, protein-protein interaction network mapping, and multi-algorithm feature selection (LASSO, SVM-RFE, Random Forest) were performed, and candidate biomarkers were validated using an independent bulk RNA-seq dataset (GSE57345).</p><p><strong>Results: </strong>Thirteen major cardiac cell types were identified, with macrophages showing the highest transcriptional heterogeneity. We resolved four macrophage subtypes and mapped bifurcating disease-associated differentiation trajectories, revealing distinct activation patterns of ferroptosis- and anoikis-related pathways. Ferroptosis-associated genes and anoikis-associated genes displayed subtype-specific enrichment and significant differential activation in HF. Pseudotime analysis demonstrated that suppression of ferroptosis and anoikis was linked to late-stage, HF-enriched macrophage states. Key biomarkers-including CD163, FPR1, and VSIG4-achieved robust diagnostic performance (AUC > 0.80) in discriminating HF phenotypes.</p><p><strong>Conclusions: </strong>This is the first study to integrate scRNA-seq, differentiation trajectory inference, and PCD pathway scoring to define the context-dependent engagement of ferroptosis and anoikis in macrophage subtypes in HF. The identification of subtype-specific biomarkers and functional states provides novel mechanistic insight and potential diagnostic and therapeutic targets, underscoring the value of high-resolution immune profiling for precision immunology in cardiovascular disease.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1604226"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Clinical and immunological spectrum of MHC class I deficiency: insights from a long-term cohort with two novel mutations. MHC I类缺陷的临床和免疫学谱:来自两个新突变的长期队列的见解。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-10-07 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1675097
Sule Haskologlu, Aydan Ikinciogullari, Candan Islamoglu, Sevgi Kostel Bal, Deniz Bayrakoglu, Serife Erdem, Zeynep Ceren Karahan, Omur Ardeniz, Caner Aytekin, Aylin Heper, Serdar Ceylaner, Figen Dogu
{"title":"Clinical and immunological spectrum of MHC class I deficiency: insights from a long-term cohort with two novel mutations.","authors":"Sule Haskologlu, Aydan Ikinciogullari, Candan Islamoglu, Sevgi Kostel Bal, Deniz Bayrakoglu, Serife Erdem, Zeynep Ceren Karahan, Omur Ardeniz, Caner Aytekin, Aylin Heper, Serdar Ceylaner, Figen Dogu","doi":"10.3389/fimmu.2025.1675097","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1675097","url":null,"abstract":"<p><strong>Background: </strong>Major histocompatibility complex (MHC) Class I deficiency is a rare form of primary immunodeficiency that typically presents with recurrent sinopulmonary infections, bronchiectasis, and granulomatous skin lesions during late childhood or adolescence.</p><p><strong>Methods: </strong>This retrospective study describes the clinical, immunological, and long-term follow-up data of 11 patients diagnosed MHC Class I deficiency.</p><p><strong>Results: </strong>The cohort included 11 patients (6 males, 5 females) with a median age of 26 years (range 19-44). The median age at diagnosis was 19 years, with a diagnostic delay of 14 years. Bronchiectasis was seen in 10 patients, granulomatous skin lesions in 6, uveitis in 5, and nasal septum perforation in 3. All but one patient survived during a median follow-up of 11 years. HLA-ABC expression ranged from 0% to 73%, with persistently low mean fluorescence intensity (0.4-3.8). IgM levels were reduced in 7 patients. Ten patients were persistently positive for anti-rubella IgM, including all six with granulomatous skin lesions. Immunophenotyping revealed reduced CD3<sup>+</sup> (n=2), CD4<sup>+</sup> (n=3), CD8<sup>+</sup> (n=3), CD19<sup>+</sup> (n=5), CD3<sup>-</sup>CD16<sup>+</sup>CD56<sup>+</sup> (n=3), CD19+ IgM-27+ IgD- (switched memory B cells) (n=7), and CD19+ IgM-27+ IgD+ (marginal zone B cells) (n=8). All patients had elevated γδ+ T cells, and NK cells were reduced in three. Seven patients had TAP1 and four had TAP2 mutations, with no significant genotype-phenotype differences.</p><p><strong>Conclusion: </strong>MHC Class I deficiency presents a broad clinical spectrum from asymptomatic to life-threatening disease. Granulomatous tissue damage and uveitis contributed to morbidity. Persistent rubella-specific IgM in most patients, including those without granulomas, is a novel serologic finding that may reflect altered antiviral immunity. Its clinical significance remains uncertain and, further studies with tissue-based viral detection are needed to clarify this observation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1675097"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Glycolytic reprogramming during microglial polarization in neurological diseases. 神经系统疾病中小胶质细胞极化过程中的糖酵解重编程。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-10-07 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1648887
Xiaoting Li, Congcong Fang, Yina Li, Xiaoxing Xiong, Xu Xu, Lijuan Gu
{"title":"Glycolytic reprogramming during microglial polarization in neurological diseases.","authors":"Xiaoting Li, Congcong Fang, Yina Li, Xiaoxing Xiong, Xu Xu, Lijuan Gu","doi":"10.3389/fimmu.2025.1648887","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1648887","url":null,"abstract":"<p><strong>Background: </strong>Microglia, the resident immune cells of the central nervous system (CNS), play pivotal roles in the onset and progression of various neurological disorders. Owing to their remarkable plasticity, microglia can adopt diverse phenotypic states in response to distinct microenvironmental cues. Over the past decades, accumulating evidence has demonstrated that immune cell metabolism critically regulates their polarization and effector functions through a process termed metabolic reprogramming, in which glucose metabolism is particularly central. Glycolytic reprogramming underlies the entire polarization process, and elucidating its mechanisms may enable targeted modulation of microglial activity to mitigate their deleterious effects in CNS pathologies, thereby offering novel therapeutic avenues for these diseases.</p><p><strong>Aim of the review: </strong>This paper summarizes what is known about microglial polarization and glycolytic reprogramming and explores their important roles in the development of neurological diseases. The link between microglial metabolomics and epigenetics in neurological disorders requires further study.</p><p><strong>Key scientific concepts of the review: </strong>Microglia exhibit distinct phenotypic states at different stages of central nervous system (CNS) disorders, and these polarization processes are closely coupled with glucose metabolic reprogramming. Proinflammatory microglia predominantly rely on glycolysis, whereas reparative or anti-inflammatory phenotypes primarily utilize oxidative phosphorylation. Targeting glycolytic pathways to limit the polarization of microglia toward proinflammatory states has emerged as a promising therapeutic strategy for CNS diseases.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1648887"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Machine learning insights into vaccine adjuvants and immune outcomes. 机器学习对疫苗佐剂和免疫结果的见解。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-10-07 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1654060
Yuhyun Ji, Kavitha Bekkari, Ruchin Patel, Mohammed Shardar, Geoffrey A Walford, SamMoon Kim, Yaping Liu, Willis Read-Button, Kristina Tracy, Jennifer Kriss, Colleen Barr, Marissa Wolfle, Shailaa Kummar, Celia LaPorta, Madison Radnoff, Milan Ghodasara, Jian Xiong, William J Smith, Kunal Bakshi, Nicole L Sullivan, Nicholas Murgolo
{"title":"Machine learning insights into vaccine adjuvants and immune outcomes.","authors":"Yuhyun Ji, Kavitha Bekkari, Ruchin Patel, Mohammed Shardar, Geoffrey A Walford, SamMoon Kim, Yaping Liu, Willis Read-Button, Kristina Tracy, Jennifer Kriss, Colleen Barr, Marissa Wolfle, Shailaa Kummar, Celia LaPorta, Madison Radnoff, Milan Ghodasara, Jian Xiong, William J Smith, Kunal Bakshi, Nicole L Sullivan, Nicholas Murgolo","doi":"10.3389/fimmu.2025.1654060","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1654060","url":null,"abstract":"<p><p>Adjuvants boost the immune response to vaccine antigens, serving as key components in safe and effective vaccines. However, selecting a suitable adjuvant for a new vaccine can be challenging. This is due to the wide variety of adjuvants and the many mechanisms of vaccines they are meant to enhance. Therefore, the adjuvant selection process heavily relies on empirical experiments, which are time-consuming and resource-intensive. In this study, we introduce a machine learning approach leveraging non-human primate RNA transcriptomic data to predict immunogenic antibody levels after vaccination. Furthermore, analysis of the trained deep learning models enabled the identification of immune response mechanisms that are stimulated by adjuvants. Integration of machine learning has the potential to expedite vaccine adjuvant selection by focusing on evaluating adjuvant candidates with the highest probability of success. This may ultimately facilitate the development of more effective vaccines.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1654060"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Editorial: Understanding scleroderma: symptoms, causes, treatment options, and advanced diagnostic techniques. 社论:了解硬皮病:症状、原因、治疗方案和先进的诊断技术。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-10-07 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1716460
Predrag Ostojic
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