Bahareh Ebrahimi, Hossein Kargar Jahromi, Nazanin Shafiei Jahromi, Mina Molayem
{"title":"A Systematic Review of Ocular Complications Following Different Types of Covid-19 Vaccines.","authors":"Bahareh Ebrahimi, Hossein Kargar Jahromi, Nazanin Shafiei Jahromi, Mina Molayem","doi":"10.1155/jimr/8766021","DOIUrl":"10.1155/jimr/8766021","url":null,"abstract":"<p><strong>Introduction: </strong>More than 6 million deaths from the novel coronavirus, the Coronavirus disease 2019 (COVID-19) infection, have prompted the development of several prophylactic vaccines of COVID-19. This systematic review summarizes the ocular complications of various COVID-19 vaccinations, diseases diagnosed, treatment, and risk factors.</p><p><strong>Methods: </strong>The search was done in PubMed, Web of Science (WOS), and Google Scholar databases. Manifestations were classified depending on the type of vaccines and the interval between vaccination and the onset of symptoms. Other data such as patients' age, gender, underlying diseases, and follow-up data were also extracted.</p><p><strong>Results: </strong>Initially, 10,242 articles were identified and 76 articles were eligible that among them 107 cases were reported. Ocular complications were diagnosed more often in Pfizer-BioNTech COVID-19 vaccine and Oxford-AstraZeneca COVID-19 vaccine (AstraZeneca) recipients than in others.</p><p><strong>Conclusion: </strong>This systematic review highlights a wide range of ocular complications reported after COVID-19 vaccination, the most common of which is uveitis. While most cases were mild and self-limiting, some involved reactivation of preexisting inflammatory diseases. These findings emphasize the importance of postvaccination ocular surveillance. This is particularly important in individuals with a history of ocular inflammation and suggests a potential immunological mechanism that requires further investigation.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"8766021"},"PeriodicalIF":3.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12538234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fahimeh Baghaei, Zahra Hemmat, Amir Taherkhani, Setareh Shojaei, Ali Teimoori
{"title":"Rational Design and In Silico Evaluation of a Multiepitope Vaccine Targeting the uPAR for Cancer Immunotherapy.","authors":"Fahimeh Baghaei, Zahra Hemmat, Amir Taherkhani, Setareh Shojaei, Ali Teimoori","doi":"10.1155/jimr/9126083","DOIUrl":"10.1155/jimr/9126083","url":null,"abstract":"<p><strong>Background: </strong>The urokinase plasminogen activator receptor (uPAR) plays a crucial role in cancer development and progression, making it an attractive target for immunotherapeutic strategies. This study aimed to develop a multiepitope vaccine targeting uPAR by incorporating T cell epitopes and a toll-like receptor 4 (TLR4) agonist as an adjuvant.</p><p><strong>Methods: </strong>Immunoinformatics approaches were employed to predict and select immunogenic epitopes from the uPAR protein sequence. The selected epitopes were assembled into a multiepitope vaccine construct, including a TLR4 agonist derived from <i>Mycobacterium tuberculosis</i> as an adjuvant. The vaccine candidate underwent comprehensive in silico analyses, including antigenicity, allergenicity, physicochemical properties, and structural modeling. Molecular docking and molecular dynamics (MD) simulations were performed to evaluate the vaccine's interaction with the TLR4 receptor and assess its structural stability. Also, vector design was performed using the SnapGene software, while immune response simulations were conducted with the C-ImmSim server.</p><p><strong>Results: </strong>The multiepitope vaccine construct comprised five cytotoxic T lymphocyte (CTL) epitopes, five helper T lymphocyte (HTL) epitopes, and the TLR4 agonist adjuvant. The vaccine was predicted to be nonallergenic, antigenic, and soluble, with favorable physicochemical properties. Molecular docking analysis revealed a strong binding affinity between the vaccine and TLR4, with a docking score of -334.37kcal/mol. MD simulations demonstrated the structural stability and rigidity of the vaccine-TLR4 complex. The computational immune simulation predicted a strong vaccine response with lasting antibody production, robust cellular immunity, and immunological memory formation.</p><p><strong>Conclusion: </strong>The proposed multiepitope vaccine construct, consisting of carefully selected uPAR epitopes and a potent adjuvant, exhibits promising characteristics for inducing a robust immune response against cancer cells expressing uPAR. The favorable in silico results warrant further experimental validation and preclinical studies to assess the vaccine's efficacy and potential as a cancer immunotherapeutic agent.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"9126083"},"PeriodicalIF":3.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12531433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Focus on Interferon Signature in Cutaneous Lupus Erythematosus: Novel Therapies From Better Understanding of the Pathogenesis.","authors":"Min Gao, Nenghan Zhang, Yumin Xia","doi":"10.1155/jimr/5600731","DOIUrl":"10.1155/jimr/5600731","url":null,"abstract":"<p><p>Cutaneous lupus erythematosus (CLE), a common clinical manifestation of lupus erythematosus (LE), significantly compromises patients' quality of life and social functioning due to its relatively high prevalence. While the exact pathogenesis of CLE remains incompletely understood, accumulating evidence highlights the pivotal role of interferon (IFN) as a central mediator in disease initiation and progression. Stromal cells and infiltrating immune cells within CLE lesions demonstrate elevated expression of IFN-stimulated genes (ISGs), establishing a characteristic IFN signature. IFN orchestrates multiple pathological processes, including chemokine-mediated immune cell recruitment, cutaneous inflammation cascade, and tissue fibrosis. This review systematically examines the IFN-CLE axis through an integrated analysis of in vitro and in vivo experimental data. Emerging clinical trials reveal therapeutic promise in strategies targeting plasmacytoid dendritic cells (pDCs), neutralizing IFN signaling, or blocking downstream pathways. Given the current limitations in CLE management, IFN-focused strategies may offer innovative solutions to address unmet clinical needs through precision immunomodulation.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"5600731"},"PeriodicalIF":3.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Follicular Helper T Cells: Potential Interventional Targets in Atherosclerosis.","authors":"Yuxuan Chen, Wenxin Wang, Xueli Xia, Xun Xu, Shengjun Wang, Poorani Gurumallesh","doi":"10.1155/jimr/9247816","DOIUrl":"10.1155/jimr/9247816","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a disease characterized by the presence of lesions in the arterial intima throughout the circulatory system. Lipid metabolism disorders form the pathological basis of AS. Immune injury resulting from lipid deposition, which is regulated by various cytokines, significantly contributes to disease progression. Follicular helper T (Tfh) cells are essential in the humoral immune response. The abnormal expression of surface molecules and cytokines by Tfh cells may contribute to the onset and progression of AS. Additionally, an increase in the Tfh cell population contributes to the progression of AS and coronary artery disease (CAD). Therefore, the targeting of Tfh cells and their associated functional molecules could serve as a promising therapeutic strategy against AS. This review summarizes current insights into the role of Tfh cells in AS and highlights their potential as therapeutic targets.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"9247816"},"PeriodicalIF":3.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12518169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TingTing Cao, Ying Wang, Juan Zhang, Wei Song, WeiJie Dai, GuoZhong Ji, Poorani Gurumallesh
{"title":"Leonurine Alleviates DSS-Induced Colitis in Mice by Regulating Pancreatic Secretion Pathway and Gut Microbiota.","authors":"TingTing Cao, Ying Wang, Juan Zhang, Wei Song, WeiJie Dai, GuoZhong Ji, Poorani Gurumallesh","doi":"10.1155/jimr/6626309","DOIUrl":"10.1155/jimr/6626309","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease (IBD). Leonurine is an active component in <i>Leonurus japonicus</i>, involved in several processes such as inflammation, oxidation, and other processes. This study found that symptoms of colitis induced by 3% dextran sulfate sodium (DSS) solution in C57BL/6 mice were significantly alleviated after administration of leonurine, in terms of reduced body weight, shortened colon length, disease activity index (DAI), and colonic pathological damage. The expression of the tight junction (TJ) protein claudin-1 and occludin markedly increased, the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) significantly decreased. Findings from transmission electron microscopy (TEM) and intestinal permeability assessment experiments indicated that leonurine ameliorates the intestinal barrier. Leonurine regulated the pancreatic secretion pathway, significantly reduced the expression levels of <i>Cela2a</i> and <i>Cela3b</i>, and clearly decreased the abundance of Rikenellaceae_RC9_gut_group, UBA1819, <i>Enterococcus</i>, and <i>Oscillibacter</i>. We proposed that leonurine may improve DSS-induced colitis by regulating the pancreatic secretion pathway, modulating the gut microbiota, and improving intestinal barrier, potentially becoming a candidate for the treatment of UC.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"6626309"},"PeriodicalIF":3.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12514016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to \"Luteolin Regulates the Differentiation of Regulatory T Cells and Activates IL-10-Dependent Macrophage Polarization against Acute Lung Injury\".","authors":"","doi":"10.1155/jimr/9786427","DOIUrl":"10.1155/jimr/9786427","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1155/2021/8883962.].</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"9786427"},"PeriodicalIF":3.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12512325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne De Meyst, Kelly Lemeire, Amanda Gonçalves, Niels Vandamme, Daisy Vanrompay
{"title":"Unmasking Budgerigar Splenic Leukocyte Populations With Single-Cell Transcriptomics and Multiplex RNA In Situ Hybridization.","authors":"Anne De Meyst, Kelly Lemeire, Amanda Gonçalves, Niels Vandamme, Daisy Vanrompay","doi":"10.1155/jimr/1554863","DOIUrl":"10.1155/jimr/1554863","url":null,"abstract":"<p><p>The current understanding of the avian immune system primarily stems from research conducted in chickens, given their economic significance as a food source. Extending the research to other avian species like <i>Psittaciformes</i> requires the use of label-free techniques. Therefore, budgerigar (<i>Melopsittacus undulatus</i>) splenic leukocytes were characterized in this study, with the help of an immunological toolbox, integrating single-cell transcriptomics and multiplex RNA in situ hybridization (ISH). Twenty-four distinct psittacine splenic leukocyte populations were identified and characterized, including, amongst others, germinal center (GC) B cells and regulatory T cells (Tregs). For each of these 24 populations, markers were defined for subsequent use in immunological assays. To further examine splenic organization, multiplex RNA ISH was applied, successfully characterizing six out of the nine selected markers. This study showed that the psittacine immune system closely mirrors that of chickens. However, a detailed, comprehensive examination was hindered by the lack of a complete sequenced and annotated budgerigar genome and the limited number of replicates. Consequently, further investigation is imperative to advance our understanding of the avian immune system.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"1554863"},"PeriodicalIF":3.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bogusz Aksak-Wąs, Karolina Skonieczna-Żydecka, Miłosz Parczewski, Rafał Hrynkiewicz, Filip Lewandowski, Karol Serwin, Kaja Mielczak, Adam Majchrzak, Franciszek Lenkiewicz, Paulina Niedźwiedzka-Rystwej, Poorani Gurumallesh
{"title":"Influence of PD-1 and PD-1L Immune Exhaustion Receptors on Immune Reconstruction in People Living With HIV.","authors":"Bogusz Aksak-Wąs, Karolina Skonieczna-Żydecka, Miłosz Parczewski, Rafał Hrynkiewicz, Filip Lewandowski, Karol Serwin, Kaja Mielczak, Adam Majchrzak, Franciszek Lenkiewicz, Paulina Niedźwiedzka-Rystwej, Poorani Gurumallesh","doi":"10.1155/jimr/2462382","DOIUrl":"10.1155/jimr/2462382","url":null,"abstract":"<p><strong>Introduction: </strong>The progressive immunological impairment associated with human immunodeficiency virus (HIV) infection is partially mediated by the programmed cell death protein-1 (PD-1)/programed death-ligand 1(PD-L1) inhibitory pathway. This investigation aims to evaluate the influence of PD-1 on immune reconstitution in patients undergoing antiretroviral therapy (ART), with data visualized through principal component analysis (PCA).</p><p><strong>Materials and methods: </strong>Data from 52 ART-treated individuals achieving viral suppression were analyzed over 12 months. CD4+, CD8+, CD19+, and PD-1/PD-L1 expressions were quantified via flow cytometry at baseline and after 12 months, and immune recovery was assessed at CD4+ thresholds of 500 and 800/μL and CD4+/CD8+ ratios of >0.8 and >1.0 using linear and logistic regression. PCA was applied to visualize clustering of immune recovery patterns based on PD-1/PD-L1 expression levels and immune cell counts, with statistical significance evaluated using ANOVA.</p><p><strong>Results: </strong>The analyzed group of 52 patients was predominantly male (65.4%; <i>n</i> = 34). PD-1/PD-L1 expression showed modest associations with immune recovery. Higher PD-L1 expression on CD3+ T-cells at baseline was associated with a reduced likelihood of recovery to CD4+>500/μL (OR: 0.79; 95%CI: 0.62-0.99; <i>p</i> = 0.04). Linear regression demonstrated that increased PD-L1 on CD4+ T-cells and PD-1 on CD19+ B-cells positively correlated with higher CD4+/CD8+ ratios at follow-up (coefficient: 0.035 and 0.03, respectively; <i>p</i> < 0.02), while logistic regression indicated that higher PD-1 on CD3+ T-cells increased the odds of recovery to CD4+>500/μL (OR: 1.03; 95% CI: 1.0036-1.07); = 0.03). Notably, this weak signal may result from a general increase in the number of lymphocytes during therapy. PCA did not reveal significant clustering of immune recovery patterns.</p><p><strong>Conclusion: </strong>PD-1 and PD-L1 expressions on immune cells are weakly associated with immune recovery metrics in individuals undergoing ART. Further research is needed to explore their role in immune reconstitution and potential clinical applications.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"2462382"},"PeriodicalIF":3.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification and Validation of Fibroblast-Associated Genes in Osteoarthritis Based on High-Dimensional Weighted Gene Coexpression Network Analysis.","authors":"Juan Xiao, Wei Lei, Hao Zhang, Feng Niu, Qunhai Wu, Honglin Pi, Poorani Gurumallesh","doi":"10.1155/jimr/5547701","DOIUrl":"10.1155/jimr/5547701","url":null,"abstract":"<p><p><b>Background:</b> Osteoarthritis (OA) is a degenerative joint disease with articular cartilage destruction, triggering a pro-inflammatory response. The aim of this study was to screen key genes associated with fibroblasts based on single-cell transcriptomic data and explore their potential value in OA diagnosis. <b>Methods:</b> We obtained RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) data of OA from the Gene Expression Omnibus (GEO) database. The CellChat package for cell-to-cell communication analysis and identification of possible ligand-receptor pairs. High-dimensional weighted gene coexpression network analysis (hdWGCNA) was applied to identify the gene modules, and the key genes in the modules were identified and subjected to functional enrichment analysis. Subsequently, limma packages were used to screen for differentially expressed genes (DEGs) between OA and its control samples. Finally, the R package multipleROC was used to test the diagnostic potential of the screened key genes and to construct an OA diagnostic model using the rms package. <b>Result:</b> Eight cell populations were identified and annotated based on scRNA-seq and the percentage of fibroblasts was the highest. The cell-cell communication analysis has suggested that the highest communication probability was seen between mesenchymal cells/T cells and fibroblasts through the pairs of CD99-CD99. The hdWGCNA analysis suggested that genes of modules M3, M4, M5, M6, and M8 (50 genes in total) were highly expressed in fibroblasts. Thereafter, we obtained 394 DEGs in OA and its control samples and took intersections with 50 modular genes and identified seven central genes (including apolipoprotein D <i>[APOD]</i>, biglycan <i>[BGN]</i>, <i>MXRA5</i>, <i>THY1</i>, <i>C1QTNF3</i>, dermatopontin [<i>DPT]</i>, and osteoglycin <i>[OGN]</i>). The constructed diagnostic models showed good predictive performance with all area under the curve (AUC) values >0.8. Finally, a satisfactory diagnostic model was established using these seven genes, and the differences in mRNA expression levels of these genes in OA and normal tissues were verified. <b>Conclusion:</b> For the first time, our study systematically screened and validated key genes with diagnostic potential based on fibroblast-specific single-cell data in combination with hdWGCNA, providing a new theoretical basis and research direction for molecular typing and diagnosis of OA.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"5547701"},"PeriodicalIF":3.6,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Dynamic Expression Changes of Neutrophil Extracellular Traps in Mouse Apical Periodontitis: A Potential Correlation With IL-17.","authors":"Zihan Ma, Xiaoyue Sun, Ying Lin, Zijun Wang, Qing Nie, Jingjing Yu, Jingwen Yang, Lingxin Zhu","doi":"10.1155/jimr/8039031","DOIUrl":"10.1155/jimr/8039031","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) consist of decondensed chromatin and antimicrobial proteins, which are released from neutrophils and have been implicated in several inflammatory diseases. NETs and interleukin (IL)-17 constitute a feed-forward loop that promotes immunopathological development of inflammation. Therefore, this study aimed to investigate the dynamic distribution of NETs and their colocalization with IL-17 during the progression of apical periodontitis in established mouse models. Apical periodontitis was induced in mice by exposing the pulp of the mandibular first molars, with mandibles harvested on day 0, 7, 14, 21, and 28 after pulp exposure. Micro-CT and high-resolution X-ray scanning showed progressive increases in both the area and volume of periapical lesions from day 0 to day 28. Osteoclasts in the periapical lesions were identified using tartrate-resistant acid phosphatase (TRAP) staining, with their numbers peaking on day 21. Immunofluorescence staining was performed for citrullinated histone H3 (CitH3), myeloperoxidase (MPO), neutrophil elastase (NE), and IL-17 to localize NETs and their colocalization with IL-17 in lesions. NETs, which were visible on day 7 and increased gradually until day 21, primarily located in inflammatory infiltration areas of the periapical tissue. Additionally, western blot analysis showed increased CitH3 expression in periapical lesions on day 21 after pulp exposure, further confirming the presence of NETs. Both RT-qPCR and enzyme-linked immunosorbent assay (ELISA) revealed increased IL-17 expression in periapical lesions. The colocalization of CitH3, the major component of NETs and IL-17 peaked on day 21 after pulp exposure. Furthermore, in vitro experiments demonstrated that IL-17 promoted NETs formation under lipopolysaccharide (LPS)-simulated inflammatory conditions. Our findings indicated that NETs expression changed dynamically and suggested a feedback loop between NETs and IL-17 during the development of apical periodontitis in mouse models.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"8039031"},"PeriodicalIF":3.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}