Frontiers in Immunology最新文献

{"title":"Research progress in RBC alloimmunization.","authors":"Zike Fu, Xinxin Hao, Wa Gao, Quishi Wang","doi":"10.3389/fimmu.2025.1677581","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1677581","url":null,"abstract":"<p><p>Red blood cell (RBC) alloimmunization is a common and clinically significant immunological phenomenon in transfusion medicine, pregnancy management, and organ transplantation. It involves complex interactions between RBC antigens and the host immune system. Recent studies have revealed that RBCs are not merely passive immunological targets but also play more complex roles in the initiation and regulation of alloimmune responses. This review begins with the immunogenic properties of RBC antigens and systematically outlines the molecular mechanisms of alloimmunization, including T cell-dependent and-independent responses, functional differentiation of dendritic cells and marginal zone B cells, complement regulation, and multiple pathways of immune tolerance. On this basis, we highlight key factors influencing the occurrence of alloimmunization, such as antigen characteristics, recipient inflammatory status, donor RBC quality, underlying disease conditions, transfusion-related variables, and other potential mechanisms. Using sickle cell disease (SCD) and hemolytic disease of the newborn (HDFN) as representative models, we further explore the distinctive features and clinical implications of RBC alloimmunization in different disease contexts. This review aims to provide a systematic framework for understanding RBC-mediated immune responses and to establish a theoretical foundation for developing individualized immunomodulatory strategies.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1677581"},"PeriodicalIF":5.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354599","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}

{"title":"Th17/Treg imbalance in inflammatory bowel disease: immunological mechanisms and microbiota-driven regulation.","authors":"Yuyuan Hu, Yuhang Yang, Yan Li, Qiang Zhang, Wei Zhang, Jinghan Jia, Zhuoyi Han, Jinxi Wang","doi":"10.3389/fimmu.2025.1651063","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1651063","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a group of conditions characterized by chronic and recurrent intestinal inflammation, primarily including Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis of IBD is closely linked to abnormal immune responses, particularly T-cell mediated immune reactions. Th17 cells promote persistent intestinal inflammation by secreting pro-inflammatory cytokines such as IL-17, while regulatory T (Treg) cells help maintain immune homeostasis by secreting anti-inflammatory cytokines like IL-10 and TGF-β. In patients with IBD, Th17 cell function is enhanced, whereas Treg cell function is impaired or their numbers are reduced, leading to an imbalance in the immune system and exacerbating intestinal inflammation. The gut microbiota plays a crucial role in the immune regulation of IBD. Dysbiosis can lead to excessive activation of Th17 cells and suppression of Treg cell function, further aggravating clinical symptoms. Studies have shown that restoring gut microbiota balance through probiotics, antibiotics, dietary interventions, or fecal microbiota transplantation can not only improve immune responses but also restore the balance between Th17 and Treg cells, which has a positive impact on IBD treatment. This review summarizes how gut microbiota modulates the Th17/Treg cell balance to influence IBD immune responses and explores therapeutic strategies targeting Th17/Treg balance, including cytokine antagonists and immunosuppressive agents, which provide new directions and approaches for clinical IBD treatment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1651063"},"PeriodicalIF":5.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354362","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}

{"title":"Single-cell transcriptomic analysis reveals epithelial and microenvironmental heterogeneity in small cell carcinoma of the esophagus.","authors":"Xiaolei Yin, Xiaopeng Li, Lili Mi, Jiaojiao Hou, Fei Yin","doi":"10.3389/fimmu.2025.1672587","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1672587","url":null,"abstract":"<p><strong>Background: </strong>Small cell carcinoma of the esophagus (SCCE) is a rare and highly aggressive malignancy with limited therapeutic options and poor prognosis. The paucity of clinical specimens and lack of established experimental models have hindered a comprehensive understanding of its cellular heterogeneity and tumor microenvironment.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing on SCCE samples, and integrated them with publicly available scRNA-seq datasets from esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and adjacent normal tissues (NT) from ESCC and EAC cases. An integrative transcriptomic analysis was conducted to identify cell types, infer malignant states, reconstruct differentiation trajectories, evaluate immune landscapes, and investigate fibroblast subtypes and cell-cell communication networks.</p><p><strong>Results: </strong>SCCE tumors were characterized by a predominance of malignant epithelial cells and exhibited a profoundly immunosuppressed phenotype, with reduced immune infiltration and widespread downregulation of immune checkpoint genes. Malignant epithelial cells showed pronounced chromosomal instability and were classified into three transcriptionally distinct subtypes with divergent differentiation trajectories. The tumor microenvironment featured a complex stromal compartment, with enrichment of extracellular matrix fibroblasts (eCAFs) characterized by elevated ELF3 regulatory activity, and collagen-driven signaling predominantly mediated by inflammatory CAFs (iCAFs). SCCE also showed the most intricate cell-cell communication network among esophageal cancer subtypes.</p><p><strong>Conclusion: </strong>Our single-cell atlas offers a detailed view of the cellular heterogeneity and microenvironmental complexity of SCCE, highlighting its distinct tumor architecture, immune exclusion, and stromal reprogramming. These findings provide a valuable resource for understanding SCCE biology and form a basis for future mechanistic and exploratory biological investigations.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1672587"},"PeriodicalIF":5.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354367","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}

{"title":"A novel role for Hsc70-4 in blood cell differentiation in <i>Drosophila</i>.","authors":"Bayan Kharrat, Erika Gábor, Péter Vilmos, Lauren M Goins, Viktor Honti","doi":"10.3389/fimmu.2025.1641695","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1641695","url":null,"abstract":"<p><p>The <i>Drosophila</i> lymph gland serves as an excellent model for studying blood cell development, closely mirroring the key components of mammalian hematopoietic niches: blood cell progenitors, mature blood cells, and niche cells that secrete signals to regulate progenitor maintenance. In the <i>Drosophila</i> larva, two primary types of mature hemocytes exist: macrophage-like plasmatocytes and platelet-like crystal cells. In cases of immune challenge or neoplastic conditions, a third type of hemocyte, the lamellocyte, appears to encapsulate large invaders that plasmatocytes cannot phagocytose. Importantly, the spontaneous appearance of lamellocytes in unchallenged larvae indicates defects in progenitor maintenance or blood cell fate regulation. In this study, we uncover a novel role for the molecular chaperone Hsc70-4 in suppressing lamellocyte differentiation across all three domains of the lymph gland. We show that Hsc70-4 depletion in the niche induces non-apoptotic cell death and oxidative stress, which in turn drives non-cell-autonomous lamellocyte differentiation via the Akt/Foxo pathway. In blood cell progenitors, particularly distal progenitors, Hsc70-4 loss promotes cell-autonomous lamellocyte differentiation, thereby diminishing the progenitor pool. Furthermore, silencing <i>Hsc70-4</i> in mature hemocytes elicits a strong immune response characterized by primary lobe disintegration, lamellocyte transdifferentiation, and melanotic tumor formation. Together, these findings highlight the multifaceted roles of Hsc70-4 in <i>Drosophila</i> hematopoiesis, offering valuable insights that could enhance our understanding of the role of its orthologue in mammals and humans.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1641695"},"PeriodicalIF":5.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354393","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}

{"title":"Case Report: Novel endoscopic characteristics of early-stage autoimmune gastritis from two cases: the fog is lifting.","authors":"Yiming Song, Jianing Yan","doi":"10.3389/fimmu.2025.1550919","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1550919","url":null,"abstract":"<p><p>With the development of research, the clinical characteristics of autoimmune gastritis (AIG) have become much clearer. However, due to its occult endoscopic appearance, it remains difficult to diagnose early, including ultra-early AIG. More cases and typical clinical characteristics should be proposed and concluded to guide clinicians. Hence, we selected two novel cases of early AIG and summarized their common endoscopic features in order to improve diagnostic ability. We found two interesting features for early AIG: 1) deep reticular blood vessels in the lower part of the cardia mucosa and 2) various manifestations of crypt opening shown on narrow-band imaging (NBI) magnification, such as dilation, pinhole-like, shrinkage, and disappearance. Future studies promise even more progress with the hope that these features can be found in more cases.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1550919"},"PeriodicalIF":5.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354457","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}

{"title":"High mesothelin expression is associated with low cytotoxic T cell infiltration in pancreatic cancer.","authors":"Oliver Liang, Amy L White, Timothy Fielder, Joo-Shik Shin, Sharon M Sagnella, Ulf Schmitz, Dannel Yeo","doi":"10.3389/fimmu.2025.1651687","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1651687","url":null,"abstract":"<p><strong>Objectives: </strong>Mesothelin (MSLN) is a cell-surface glycoprotein overexpressed in the majority of pancreatic ductal adenocarcinoma (PDAC) cases and represents a promising immunotherapeutic target. Despite studies and clinical trials investigating MSLN-targeted immunotherapies, its biological role in PDAC carcinogenesis and influence on the tumor microenvironment remain poorly characterized. This study aims to investigate MSLN expression patterns in PDAC and assess their relationship to clinical outcomes and the immune microenvironment.</p><p><strong>Methods: </strong>MSLN expression in 74 PDAC patients was evaluated by immunohistochemistry staining on a tissue microarray and correlated with clinicopathological features and survival outcomes. Complementary analyses of publicly available transcriptomic datasets (bulk RNA-seq and single-cell RNA-seq) were performed to characterize associations between MSLN expression and the tumor immune microenvironment with immunohistochemical validation.</p><p><strong>Results: </strong>High MSLN expression (H-score ≥ 62) was associated with improved relapse-free survival (p = 0.021) and with increased patient age (p = 0.036). Transcriptomic analyses revealed high MSLN expression was associated with an immunosuppressive microenvironment characterized by reduced immune reactivity and diminished cytotoxic T cell infiltration. Immunohistochemical validation confirmed a trend toward decreased stromal cytotoxic T cell abundance with increasing MSLN expression.</p><p><strong>Conclusion: </strong>This study revealed an inverse relationship between MSLN expression and cytotoxic T cell infiltration in PDAC, despite a trend toward improved relapse-free survival in MSLN-high tumors. These findings have important implications for MSLN-targeted immunotherapies and suggest that addressing the immunosuppressive microenvironment may be necessary to optimize their current responses in PDAC.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1651687"},"PeriodicalIF":5.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354460","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}

{"title":"Insights into tumor vaccines for elderly individuals in the context of immunosenescence.","authors":"Chenglong Li, Zhujun Chen, Changyu Zhu, Min Chen, Jinqi Li, Lei Zhong, Yingying Hou","doi":"10.3389/fimmu.2025.1660874","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1660874","url":null,"abstract":"<p><p>The global burden of cancer is increasing tremendously, particularly among individuals aged 60 years and older, and has emerged as a critical public health concern. Cancer vaccine-induced immunity can recognize and eliminate tumor cells with high specificity and low toxicity. Nevertheless, immunosenescence increases the risk and severity of cancers in elderly individuals while impairing vaccine-induced immunity. Furthermore, much oncology research has predominantly focused on adults, often neglecting the potential contributions of aging individuals to tumor progression. Elucidating the interactions between the immunosenescent microenvironment and tumorigenesis can inspire the development of more effective cancer vaccines tailored to the characteristics of elderly individuals, thereby alleviating the global cancer burden. In this review, we analyze how the immunosenescent microenvironment impacts tumor development and summarize existing strategies aimed at enhancing cancer vaccine efficacy, drawing inspiration from insights into immunosenescence. We believe that this review will inspire efforts toward creating individualized cancer vaccines for the elderly.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1660874"},"PeriodicalIF":5.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354523","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}

{"title":"Is the MAPK ERK5 the nexus from FAO to NK cell-mediated metastasis immune surveillance?","authors":"Martin Villalba, Delphine Gitenay, Sara Zemiti, Jean-François Rossi, Mauricio Campos-Mora","doi":"10.3389/fimmu.2025.1641865","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1641865","url":null,"abstract":"<p><p>Mammalian cells adapt to their environment by reshaping their metabolism. Increased fatty acid oxidation (FAO) enables metastatic cells to enhance their motility and colonize new niches, where the fatty acid transporter CD36 functions as both marker and driver of this process. The MAPK ERK5 regulates CD36 expression, FAO, and the epithelial-mesenchymal transition (EMT), a critical initial step in metastasis. Contrary to popular belief, metastasis is a highly inefficient process, in part due to natural killer (NK) cell immune surveillance. This cytotoxic lymphocyte lineage detects inhibitory and activating ligands on target cells to determine their fate. During EMT, the expression of specific ligands on metastatic cells triggers their recognition by NK cells. Interestingly, several of these ligands are regulated by ERK5. We hypothesize that ERK5 may serve as a central link between FAO, metastasis, and immune surveillance. Here, we review current knowledge and available evidence regarding ERK5 expression in tumor cells and its role in cancer cell migration and metastasis and speculate in the potential role of ERK5 in immune recognition and the clearance of metastasis by NK cells.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1641865"},"PeriodicalIF":5.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354533","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}

{"title":"Immunoadjuvanted influenza vaccine immunogenicity in children with type 1 diabetes over two consecutive seasons.","authors":"Mikhail Petrovich Kostinov, Maria Alexandrovna Kvasova, Alla Anatolievna Tarasova, Anna Vlasenko, Elena Vladimirovna Kolbasina, Darya Alexandrovna Bydanova, Aristitsa Kostinova, Valentina Polishchuk, Isabella Abramovna Khrapunova, Marina Loktionova, Andrey Viktorovich Linok, Yulia Alekseevna Dagil, Elena Petrovna Foshina","doi":"10.3389/fimmu.2025.1597619","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1597619","url":null,"abstract":"<p><p>Patients with diabetes mellitus face a significantly higher risk of severe influenza and its complications. The purpose of this study was to investigate the immunogenicity of the trivalent immunoadjuvanted subunit influenza vaccine in children with type 1 diabetes (T1D) over two consecutive seasons.</p><p><strong>Methods: </strong>A prospective non-randomized study during 2 epidemic seasons included 146 children with T1D at the age of 12.0 (9.0-14.0) years; the main group consisted of 81 patients vaccinated against influenza, the control group included 65 unvaccinated children. Antibody (Ab) levels to influenza viruses were evaluated using the hemagglutination inhibition assay before vaccination, one month and 12 months after vaccination.</p><p><strong>Results: </strong>Over two seasons, vaccinated children with T1D demonstrated a significant increase in Ab against all three vaccine strains 1 month post-vaccination, irrespective of their initial specific Ab levels. Differences in the persistence of antibodies 12 months post-vaccination were observed between children initially seronegative for A/H1N1 and A/H3N2 strains, who exhibited lower antibodies levels and fold increases, and those initially seropositive. Vaccinated seropositive children experienced significant post-vaccination Ab increases, surpassing levels in initially seronegative patients. Regardless of the epidemiological season, vaccination significantly increased the chance of achieving a seroprotective Ab level within one month for the A/H1N1 strain by 4.7 [2.9-9.7] (χ²M-H = 16.4, p < 0.001), for the A/H3N2 strain by 15.8 [5.9-41.4] (χ²M-H = 44.0, p < 0.001), and for strain B by 14.8 [6.5-33.6] (χ²M-H = 46.2, p < 0.001). Twelve months post-vaccination, Ab persistence was highest for the B strain, with levels 7.2 [3.2-16] times higher than in unvaccinated children, regardless of the season. Persistence of antibodies to the A/H1N1 strain was season-dependent (lower in the 2015-2016 season) and 2.5 [1.3-5] times higher than in unvaccinated children (χ²M-H = 6.5, p = 0.01). Antibodies persistence to the A/H3N2 strain did not differ significantly between vaccinated and unvaccinated groups (1.0 [0.5-2.3], χ²M-H = 0.02, p = 0.89).</p><p><strong>Conclusion: </strong>Administration of the trivalent immunoadjuvanted subunit influenza vaccine in children with T1D resulted in the formation of postvaccination Ab, meeting the Committee for Proprietary Medicinal Products (CPMP) immunogenicity criteria regardless of vaccination history.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1597619"},"PeriodicalIF":5.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354543","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}

{"title":"Mechanistic insights and biomarker discovery in immune cell aging and age-associated diseases.","authors":"Prabhat Upadhyay, Aamir Suhail, Pukar Khanal, Sudhir Kumar","doi":"10.3389/fimmu.2025.1637191","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1637191","url":null,"abstract":"<p><p>Immunosenescence is the progressive deterioration of immune function with aging and is driven by dynamic molecular and cellular interactions, most notably the chronic low-grade inflammation (inflammaging). This inflammatory state arises from lifelong antigen exposure, environmental stress, and hormonal shifts, culminating in paradoxical immune dysfunction: innate immune cells exhibit numerical expansion but functional decline, including impaired macrophage phagocytosis and diminished dendritic cell-mediated T cell priming. Advances in single-cell RNA sequencing have uncovered biomarkers of immune aging, such as upregulation of cyclin-dependent kinase inhibitors (CDKN1A/p21 and CDKN2A/p16INK4a) and senescence-associated secretory phenotype (SASP) components like IL-6, IL-8, and TNF-α. Concurrent epigenetic dysregulation, such as EZH2-dependent H3K27me3 alterations and global DNA methylation shifts, further orchestrates immune decline. The adaptive immune system undergoes profound remodeling, marked by thymic involution, skewed T cell receptor diversity, and B cell repertoire contraction, which collectively impair responses to novel antigens and vaccination efficacy. Elucidating these mechanisms provides a roadmap for targeting strategies to restore immune resilience in aging populations.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1637191"},"PeriodicalIF":5.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354584","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}