Immunologic Research最新文献

{"title":"Research on chronic urticaria and angioedema: A bibliometric analysis of Web of Science Core Collection.","authors":"Zhanyi Xu, Xieyan Gao, Zhen Zhang, Xiao Zhu, Fenglan Wang, Yang Liu, Xiaoping Yu, Tao Deng, Peiling Cai","doi":"10.1007/s12026-026-09815-w","DOIUrl":"10.1007/s12026-026-09815-w","url":null,"abstract":"<p><p>Chronic urticaria is a common mast-cell-driven inflammatory disorder characterized by recurrent wheals, angioedema, or both. Angioedema is associated with higher disease burden, impaired quality of life, and greater difficulty in clinical assessment, yet the overall research structure of chronic urticaria in the context of angioedema has not been systematically mapped. Publications were retrieved from the Web of Science Core Collection on July 14, 2026. English-language Articles and Reviews published between 1947 and 2026 were included after independent screening by two researchers, with disagreements resolved by a third researcher. Bibliometrix, VOSviewer, CiteSpace, Scimago Graphica, and GraphPad Prism were used to analyze annual output, countries, institutions, authors, journals, co-cited references, and keyword evolution. A total of 881 publications were included. Annual output increased over time, with faster growth after 2014. The United States ranked first in productivity, Germany had the highest citation count and total link strength, and Charité - Universitätsmedizin Berlin was the leading institution. The knowledge base was concentrated in mast cell biology, autoimmune mechanisms, anti-IgE therapy, and patient-reported outcomes. Keyword analysis showed a shift from early immune plausibility and idiopathic descriptions toward disease standardization, quality of life, and targeted therapy, including omalizumab and newer targeted treatments. Angioedema remained a high-frequency term and was repeatedly linked to disease burden, assessment, and treatment. The literature addressing both chronic urticaria and angioedema showed increasing emphasis on structured clinical assessment, mast-cell and autoimmune mechanisms, patient-reported outcomes, biomarker-oriented stratification, and targeted treatment. Future research should broaden international participation and evaluate clinically useful biomarkers and patient-centered outcomes across diverse populations.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684514","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}

{"title":"FUNDC1-mediated mitochondrial quality control protects against immune checkpoint inhibitor-associated cardiac injury.","authors":"Nengfeng Zhang, Yao Zhou, Hailing Li, Haiyun Liu","doi":"10.1007/s12026-026-09819-6","DOIUrl":"10.1007/s12026-026-09819-6","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) targeting PD-1 are effective cancer therapies but can cause severe myocarditis. The molecular mechanisms linking PD-1 blockade to cardiomyocyte damage are incompletely understood. We established a murine model of anti-PD-1-associated cardiac injury and used human AC16 cardiomyocytes in co-culture with CD8⁺ T cells. Global Fundc1 knockout (Fundc1-/-) mice and cardiac-specific Fundc1 reconstitution via AAV9 were employed to investigate the role of this mitophagy receptor. Cardiac function was assessed by echocardiography, and injury was evaluated through serum biomarkers, histology, and molecular analyses. Anti-PD-1 treatment induced cardiac dysfunction, myocardial T-cell infiltration, and reduced myocardial FUNDC1 expression in mice. FUNDC1 deficiency, both in vitro and in vivo, aggravated anti-PD-1-associated cardiomyocyte injury, cardiac dysfunction, inflammation, and fibrosis. Conversely, FUNDC1 overexpression or cardiac-specific Fundc1 restoration attenuated these pathological changes. Mechanistically, FUNDC1 loss was associated with altered mitophagy-related marker profiles, mitochondrial protein accumulation, increased oxidative stress, and mitochondrial functional impairment. FUNDC1-mediated mitochondrial quality control may represent an endogenous protective mechanism against anti-PD-1 antibody-associated cardiac injury.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677925","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}

{"title":"Cell-based ELISA using intact HEp-2 cells: an alternative approach for antinuclear antibody detection.","authors":"Faruk Dişli, Sedat Yıldız","doi":"10.1007/s12026-026-09816-9","DOIUrl":"10.1007/s12026-026-09816-9","url":null,"abstract":"<p><strong>Background: </strong>Antinuclear antibodies (ANAs) are serological markers of clinical importance in the diagnosis and monitoring of autoimmune diseases. This study aimed to develop a HEp-2 cell-based ELISA method as a quantitative and standardized alternative to traditional ANA detection techniques such as indirect immunofluorescence (IFA).</p><p><strong>Materials and methods: </strong>HEp-2 cells were seeded in ELISA plates at ~ 3.0 × 10⁴ cells per well and incubated. After fixation with formaldehyde and acetone, cells were quenched with 1% H₂O₂, permeabilized using Triton X-100, acetone, and methanol, and blocked with Well Champion or 1% BSA. Sixteen sera (8 ANA-positive, 8 ANA-negative), confirmed by Chorus ANA-8 and DRG ANA-8-Screen ELISA, were applied. ANA levels were measured by indirect ELISA with OD readings at 450 nm. Three HRP-conjugated secondary antibodies (anti-IgG gamma chain, Fc-specific, whole IgG) were tested.</p><p><strong>Results: </strong>Fixation and permeabilization agents did not interfere with the distinction between ANA-positive and ANA-negative samples. In the absence of quenching and when 1% BSA was used for blocking, background levels increased. Among the secondary antibodies, the anti-IgG gamma chain showed the least cross-reactivity, while Fc-specific and whole IgG antibodies had higher nonspecific binding. The assay showed an average intra- and inter-assay variation of 13.13%, with a sensitivity of 87.5% and a specificity of 81.25%.</p><p><strong>Conclusions: </strong>This study demonstrates that the HEp-2 cell-based ELISA is a feasible, promising method for detecting and quantifying ANA positivity. While it reliably distinguishes between positive and negative samples, it may serve as a practical alternative to conventional assays in research and diagnostics.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677977","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}

{"title":"Past achievements and future perspectives of personalized vaccines and the role of dendritic cells.","authors":"Mona Sadat Larijani, Anahita Bavand, Ladan Moradi, Amitis Ramezani","doi":"10.1007/s12026-026-09812-z","DOIUrl":"10.1007/s12026-026-09812-z","url":null,"abstract":"<p><p>Personalized vaccines provide the advantage of patient-specific antigen selection to optimize immune responses, a strategy extensively explored in oncology through neoantigen-targeted peptide, mRNA, and dendritic cell platforms. Peptide vaccines provide simplicity and stability though often elicit limited cytotoxic T-cell responses. What is more, mRNA vaccines lead to rapid, multiplexed neoantigen delivery, endogenous antigen processing and eventually improved immunogenic coverage. Dendritic cell-based vaccines have the potency to prime potent T-cells although this technology requires labor-intensive manufacturing and extensive production timelines. Integration with immune checkpoint inhibitors, adoptive cell therapies, and oncolytic viruses further enhances efficacy, suggesting that rational combinations may be more effective than single modalities. Recent advances in sequencing, computational epitope prediction, and bioinformatics pipelines have facilitated neoantigen prioritization and DC vaccine design, enabling more rapid and precise personalization. Hybrid vaccination strategies, such as ex-vivo mRNA-electroporated dendritic cells and in-vivo DC-targeted platforms, bridge the gap between manufacturing feasibility and potent immune activation. Emerging technologies, including AI-driven neoepitope prediction, receptor-targeted antigen delivery, biomaterial-based modulation, and distributed mRNA manufacturing, seem to be promising approaches to accelerate personalized vaccine development in future. From another point of view, lessons learned from the COVID-19 pandemic accelerated the development, large-scale deployment, and validation of mRNA vaccine platforms for infectious diseases. Host HLA diversity, prior immune history, and viral evolution create heterogeneity in immune responses, highlighting opportunities for semi-personalized or adaptive strategies. In this review, we provide a landscape of personalized vaccines, with a focus on DC-based platforms, and explore translational lessons for viral pathogens. A conceptual framework linking cancer immunotherapy and infectious disease preparedness is proposed, emphasizing hybrid personalization approaches, rapid manufacturing, and AI-enabled epitope selection. This perspective highlights how convergence of immunology, computational biology, and advanced vaccine technologies could expand the scope of personalized vaccination, from oncology to future epidemic and pandemic scenarios as well as the current challenges.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653675","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}

{"title":"Immune cells in liver transplantation: Dual roles, mechanistic insights, and targeted therapeutic strategies.","authors":"Yuanzhen Guo, Luoyang Wang, Wei Li, Xiaoli Liu, Jie Liang, Meiying Song, Xiao Wang, Yi Liu, Zhen Li, Shuai Li, Ningjing Fu, Jingzhen Cai, Bei Zhang","doi":"10.1007/s12026-026-09811-0","DOIUrl":"10.1007/s12026-026-09811-0","url":null,"abstract":"<p><p>Liver transplantation is the most effective treatment for end-stage liver disease and acute liver failure; however, organ shortage and transplant rejection remain key challenges limiting its development. In recent years, the unique role of immune cells in liver transplantation has provided new insights into the mechanisms of immune rejection and tolerance. The liver's unique immune microenvironment, dominated by innate immune cells, maintains immune tolerance through complex cell-cell interactions and cytokine networks. This article systematically reviews the dynamic roles of macrophages, neutrophils, dendritic cells (DCs), natural killer (NK) cells, and regulatory T cells (Tregs) in liver transplantation, as well as emerging therapeutic strategies derived from these findings, such as Treg infusion, machine perfusion technology, and immunometabolic regulation, all of which demonstrate immense potential. Further exploration of the heterogeneity of immune cells and their dynamic regulatory networks-particularly through the use of single-cell sequencing and spatial transcriptomics to elucidate the functional plasticity and dynamic switching mechanisms of immune cell subsets-will provide crucial guidance for achieving personalized induction of immune tolerance and optimizing liver transplant outcomes, while also laying the molecular foundation for the development of more targeted immune intervention strategies.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619966","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}

{"title":"Bone marrow SUVmax on ¹⁸F-FDG PET / CT reflects disease burden and immunosuppressive microenvironment in newly diagnosed multiple myeloma.","authors":"Hao Xiong, Huitao Zhang, Wenting Tie, Yongqiang Wang, Yijun Dong, Li Zhang, Yanhong Li, Jun Bai, Jinping Zhang, Yuxian Wang, Liansheng Zhang, Lijuan Li","doi":"10.1007/s12026-026-09804-z","DOIUrl":"10.1007/s12026-026-09804-z","url":null,"abstract":"<p><p>Disorder of the immune microenvironment plays an important role in the occurrence and development of multiple myeloma in patients. While bone marrow SUVmax on ¹⁸F-FDG PET/CT correlates with MM disease characteristics, its association with the immune microenvironment remains unclear. This study analyzed 49 newly diagnosed MM patients, dividing them into high and low SUVmax groups based on bone marrow ¹⁸F-FDG uptake. Differences in clinical characteristics, laboratory indicators, lymphocyte subsets, and cytokines were examined. Additionally, the correlation between SUVmax and these parameters was assessed. Results showed that patients with high SUVmax had a heavier disease burden, including a greater proportion of advanced-stage disease, more pathological fractures, and increased bone marrow plasma cell percentage. The high SUVmax group also exhibited a more immunosuppressive microenvironment, with a reduced proportion of CD4⁺ T cells and increased levels of regulatory T cells (Tregs) and cytokines such as IL-4 and IL-10. Correlation analysis indicated that the SUVmax of ¹⁸F-FDG uptake was positively correlated with the proportion of Treg cells and the concentrations of cytokines such as IL-4, IL-6, and IL-10, while negatively correlated with the proportion of CD4⁺ T cells.After adjustment for bone marrow plasma cell percentage, high SUVmax remained associated with decreased CD4⁺ T cells and increased Treg cells. This study suggests that bone marrow SUVmax is associated with both disease burden and immune microenvironment status in MM patients, which may provide valuable insights for disease assessment and treatment.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584271","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}

{"title":"Integrated transcriptomic analysis of peripheral blood CD4 + T cells identifies immune-associated hub genes in rheumatoid arthritis: discovery and external validation.","authors":"Haiyang Kou, Huaiquan Liu, Lingyan Lai, Shili Yang, Xinyan Zhang, Yu Sun, Yunlin Xu, Bo Chen","doi":"10.1007/s12026-026-09807-w","DOIUrl":"10.1007/s12026-026-09807-w","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by dysregulated immune responses, particularly involving CD4 + T cells. Identification of robust and reproducible molecular signatures from peripheral blood CD4 + T cells is critical for advancing biomarker discovery and understanding disease mechanisms. GSE80785 and GSE56649 (both on GPL570 platform) were integrated as the discovery cohort (n = 46; 37 RA and 9 healthy controls) after ComBat batch effect correction. GSE55235 and GSE55457 served as independent validation cohorts. Differentially expressed genes (DEGs) were identified using limma. Weighted gene co-expression network analysis (WGCNA) was performed to identify RA-associated modules. Candidate hub genes were screened by integrating PPI network topology (CytoHubba), LASSO regression, and Random Forest algorithms. External validation assessed expression consistency and diagnostic performance via ROC analysis. In the discovery cohort, 1,672 DEGs were identified (773 upregulated, 899 downregulated). WGCNA revealed 14 modules, with one module showing the strongest association with RA status. Integrative multi-algorithm analysis consistently identified four immune-associated hub genes: POLR2F, CDC42, HNRNPC, and LCN2. These genes exhibited significant correlations with immune-related pathways. In the validation cohorts, the four hub genes showed consistent expression patterns, with the combined model achieving AUC values ranging from 0.750 to 0.913. This multi-cohort study identifies POLR2F, CDC42, HNRNPC, and LCN2 as reproducible immune-associated hub genes in RA peripheral blood CD4 + T cells. The findings provide a solid foundation for further functional studies and potential biomarker development in RA.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578609","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}

{"title":"Therapeutic and pharmacological effects of quercetin in autoimmune diseases: a systematic review of preclinical and clinical evidence.","authors":"May Xin Cheong, Joen Wen Hui Lee, Mei Qian Yau","doi":"10.1007/s12026-026-09809-8","DOIUrl":"10.1007/s12026-026-09809-8","url":null,"abstract":"<p><p>Autoimmune diseases are chronic conditions that arise from the loss of immune tolerance toward the body's own tissues. Current therapeutic options are often associated with adverse effects and limited long-term efficacy. Quercetin, a naturally occurring flavonoid with well-documented antioxidant, anti-inflammatory, and immunomodulatory properties, has emerged as a potential therapeutic candidate for autoimmune conditions. This systematic review aimed to evaluate the current evidence on the pharmacological effects and therapeutic potential of quercetin in autoimmune diseases. Original in vitro studies using human-derived cell models and human clinical (in vivo) studies published in English from 2014 onwards that investigated quercetin's effects on autoimmune conditions were included, while reviews, non-English publications, and studies lacking mechanistic insights were excluded. Comprehensive searches across three electronic databases - PubMed, Scopus, and the Cochrane Library, supplemented by manual reference screening, resulted in the inclusion of thirteen studies for qualitative synthesis. Quercetin consistently demonstrated beneficial effects, including attenuation of oxidative stress, suppression of pro-inflammatory cytokines, and modulation of immune-related signaling pathways. Several clinical studies reported that quercetin alleviated disease severity and reduced tissue inflammation. Overall, quercetin exhibits pleiotropic mechanisms of action that collectively contribute to its immunomodulatory and protective effects in autoimmune diseases. However, the limited number of clinical trials and heterogeneity in study designs highlight the need for further standardized and well-controlled investigations to validate its therapeutic potential.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470379","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}

{"title":"Decoding the PI3K/Akt/mTOR-JAK/STAT signaling axis in multiple sclerosis: mechanistic crosstalk and therapeutic opportunities.","authors":"Chandrayee Banerjee, Rohit Kumar Singh, Divya Choudhary, Md Nasiruddin Khan, Pankaj Kumar Maurya, Zuber Khan, Sidharth Mehan, Rajaram Samant, Manoj Tongra","doi":"10.1007/s12026-026-09808-9","DOIUrl":"10.1007/s12026-026-09808-9","url":null,"abstract":"<p><p>Multiple Sclerosis (MS) is a chronic immune-mediated neurodegenerative disorder characterized by demyelination, axonal injury, and progressive neurological dysfunction. Emerging evidence identifies the phosphoinositide-3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways as interconnected regulators of neuroinflammation and immune dysregulation in MS. This review critically examines the mechanistic crosstalk between these signaling networks and their contribution to disease progression. Dysregulated PI3K/Akt/mTOR signaling influences T-cell activation, immunometabolic reprogramming, autophagy, and oligodendrocyte survival, whereas aberrant activation of the JAK2/STAT3 axis promotes Th17-cell differentiation, cytokine amplification, and sustained inflammatory responses within the central nervous system. Importantly, convergence between Th17/STAT3 signaling and PI3K/Akt-mediated metabolic pathways establishes a regulatory network that enhances microglial activation, blood-brain barrier disruption, and neuronal injury. The review further highlights the context-dependent role of mTOR signaling, which may simultaneously support remyelination and oligodendrocyte maturation while contributing to neurodegeneration when excessively activated. In addition to immune-cell-mediated mechanisms, emerging evidence demonstrates critical contributions of neuronal, glial, endothelial, and oligodendrocyte precursor cell signaling to MS pathology. Preclinical and clinical findings indicate that pharmacological modulation of these pathways can attenuate inflammatory responses and improve neuroprotection; however, therapeutic translation remains challenging because of their dual physiological and pathological functions. Collectively, this review provides an integrated perspective on PI3K/Akt/mTOR-JAK/STAT signaling interactions and highlights cell-specific molecular targets that may facilitate the development of more precise therapeutic strategies for MS.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470344","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}

{"title":"Transcriptomic analysis of lncRNA-miRNA-mRNA competing endogenous RNA regulatory networks in radiation-induced mouse thymic degeneration.","authors":"Fei Wang, Qing-Hua Yu, Xin-Ming Fan, Cun-Yang Guo, Si-Guang Xu, Wen-Bo Zhang, Ping Xu","doi":"10.1007/s12026-026-09805-y","DOIUrl":"10.1007/s12026-026-09805-y","url":null,"abstract":"<p><p>Excessive or inappropriate radiation can seriously harm organisms. Radiation-induced thymus injury (RITI) is a severe complication driven by dysregulated RNA networks. However, current studies have mostly focused on single non-coding RNAs or late pathological stages, and a complete competing endogenous RNA (ceRNA) regulatory network had not been constructed. The thymus tissues of C57BL/6 mice exposed to 6 Gy X-ray radiation for 24 h were analyzed by RNA-sequencing (RNA-seq) with library construction. We functionally annotated target messenger RNAs (mRNAs) and predicted long non-coding RNA (lncRNA) -targeted microRNAs (miRNAs) and miRNA-targeted mRNAs post-irradiation, to construct the lncRNA-miRNA-mRNA ceRNA regulatory axis. Furthermore, multiple experimental approaches including quantitative real-time PCR (qRT-PCR), western blotting, flow cytometry and CCK-8 cell viability assays were utilized to validate the involvement of the phosphatidylinositol 3-kinase (PI3K)-Protein Kinase B (PKB or AKT) pathway. The results revealed that after irradiation, 6214 mRNAs, 160 miRNAs, and 1999 lncRNAs were significantly upregulated while 2676 mRNAs, 165 miRNAs, and 941 lncRNAs were considerably downregulated. The most significantly altered Gene Ontology (GO) terms were angiogenesis and ameboid cell migration (Biological Process, BP), actin cytoskeleton and cell-cell junctions (Cellular Component, CC), as well as actin binding and phospholipid binding (Molecular Function, MF). A total of 333 cellular functions mediated by phosphatase and tensin homologue deleted on chromosome ten (PTEN) exhibited significant alterations, whereas 175 cellular functions regulated by 3-phosphoinositide-dependent protein kinase 1 (PDPK1) showed substantial changes. Key biological pathways, including cancer-associated pathways, the PI3K-AKT signaling pathway, the human papillomavirus infection pathway, the focal adhesion pathway, the Rap1 signaling pathway, and the cardiomyocyte calcium signaling pathway, were uncovered through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Based on the results of both GO enrichment analysis and KEGG pathway analysis, a consistent conclusion was drawn that RITI was closely associated with the PI3K-AKT signaling pathway. So the PI3K-AKT pathway was selected for experimental validation, which confirmed that it was a key regulatory pathway for thymic degeneration in RITI. A lncRNA-miRNA-mRNA ceRNA axis of RITI was successfully developed in a mouse model after irradiation. The PI3K-AKT pathway contributes to preventing radiation-induced cell death in RITI, and the differentially expressed RNAs in the initial stage of this injury may result in serious consequences.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470408","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}