International immunopharmacology最新文献

{"title":"Characterization of a novel porcine circovirus type 2a sequence and anti-viral evaluation of matrine and sanguinarine combined with network pharmacology and molecular docking.","authors":"Wen-Ting Qiao, Xin Yao, Wei-Hong Lu, Yu-Qian Zhang, Bin Zhou, Jin-Long Li","doi":"10.1016/j.intimp.2026.117551","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117551","url":null,"abstract":"<p><p>Porcine circovirus type 2 (PCV2) remains an economically significant pathogen affecting global swine herds, with emerging genetic variants raising concerns about potential immune escape from existing PCV2a-based vaccines. In this study, we identified a novel PCV2a isolate carrying four nonsynonymous substitutions (S68A, M131T, V133A, and K191A) in the capsid (Cap) protein, with the M131T/V133A substitutions located within the well-characterized conformational neutralizing epitope at residues 132-137 (KATALT→KVPAQT). To assess the functional impact of this mutation on antibody recognition, we developed a liquid-phase competitive ELISA using synthetic peptides representing the wild-type (WT) and mutant epitope sequences, together with PCV2-positive reference serum. The WT peptide effectively competed for antibody binding (inhibition rate 89.40%), whereas the mutant peptide exhibited a markedly reduced inhibition rate (40.28%), indicating impaired antibody recognition at this epitope. Combined with three-dimensional structural modeling showing altered surface charge and spatial conformation within the epitope region, these findings provide direct evidence that the KVPAQT mutation reduces neutralizing antibody binding to this critical epitope. Network pharmacology and molecular docking were then applied to assess matrine and sanguinarine targeting the mutant Cap protein. Both compounds exhibited strong binding affinities, with binding energies of -8.2 and - 7.9 kcal/mol for matrine and sanguinarine, respectively. Furthermore, in vitro antiviral assays demonstrated that both compounds effectively suppressed PCV2 replication in PK-15 cells. Overall, these findings define a clinically isolated PCV2a antigenic variant with impaired antibody recognition and establish an integrated computational-experimental platform for efficiently screening natural products against emerging PCV2 variants. This study provides a molecular basis for understanding PCV2 antigenic drift and a practical strategy for antiviral development.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"191 Pt 1","pages":"117551"},"PeriodicalIF":5.6,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to \"Immunogenicity and safety evaluation of a newly manufactured recombinant Baculovirus-Expressed quadrivalent influenza vaccine in adults 18 years old and Above: An Open-Label, phase III extension study\" [Int. Immunopharmacol. 136 (2024) 112214].","authors":"Mohammad Saleh Shahri, Setayesh Sadeghi, Delara Hazegh Fetratjoo, Hamed Hosseini, Mohammad Amin Ghobadi, Seyyedeh Maryam Afshani, Reihaneh Mirhassani, Kimiya Gohari, Forugh Havasi, Amirhossein Abdolghaffari, Behnaz Hedayatjoo, Mostafa Ghanei","doi":"10.1016/j.intimp.2026.117532","DOIUrl":"10.1016/j.intimp.2026.117532","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"190 ","pages":"117532"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-derived terpenoids in asthma: phytochemical and pharmacological perspectives from a systematic review.","authors":"Nuriye Hilal Taştekin, Fatma Uysal, Muhammet Zahit Celik, Seyfullah Oktay Arslan, Aysegul Koc Nas, Saliha Ayşenur Çam Özünlü, Halil Kara","doi":"10.1016/j.intimp.2026.117556","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117556","url":null,"abstract":"<p><strong>Background: </strong>Asthma is a chronic respiratory disorder characterized by airway inflammation, airway hyperresponsiveness (AHR), and remodeling. Structurally diverse terpenoids offer promising natural compounds with anti-inflammatory, antioxidant, and immunomodulatory properties.</p><p><strong>Objective: </strong>To address this gap, this systematic review evaluated the therapeutic potential, mechanisms of action, and translational relevance of terpenoids in experimental asthma models.</p><p><strong>Search methods: </strong>Accordingly, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, PubMed, Scopus, and Web of Science (2013-2025) were searched for peer-reviewed in vivo studies evaluating pure herbal terpenoids in asthma. Two independent reviewers conducted study selection and data extraction.</p><p><strong>Data collection and analysis: </strong>From the retrieved studies, data on terpenoids, animal models, and key asthmatic biomarkers (AHR, IgE, cytokines, immune cell infiltration, oxidative stress) were systematically extracted by phytochemical subclasses. Bias risk and methodological quality were evaluated using a modified Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)'s Risk of Bias tool.</p><p><strong>Main results: </strong>On this basis, a total of 127 studies were included, predominantly using murine ovalbumin models. Terpenoids alleviated airway inflammation, hyperresponsiveness, and remodeling by regulating Th2 cytokines, IgE, and eosinophilic infiltration. Paeoniflorin, catalpol, farnesol, curcumol, cryptotanshinone, astragaloside IV, withaferin A, and crocin showed marked anti-inflammatory, antioxidant, and anti-remodeling effects by suppressing Th2 cytokines and modulating the NF-κB, Nrf2/HO-1, and TGF-β/Smad pathways, leading to improved airway function and restored redox homeostasis.</p><p><strong>Conclusions: </strong>Overall, terpenoids demonstrate preclinical therapeutic promise in mitigating airway hyperresponsiveness and inflammation via regulating Th2/Th1 balance, oxidative stress, and fibrotic signaling. Importantly, all of the evidence synthesized here derives exclusively from preclinical animal models; no clinical trials or human pharmacological data were available, and these terpenoids therefore remain experimental candidates whose clinical relevance is not yet established. However, translational potential is constrained by methodological limitations, particularly insufficient randomization, blinding, and sample size reporting, highlighting the need for more rigorous and standardized studies.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"190 ","pages":"117556"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic prioritization and functional characterization of macrophage TXNDC17 in Ischemic heart disease.","authors":"Huanze Weng, Bo Yang, Xiaolei Fu, Jia Song, Yaowei Dai, Zhaowei Wang, Xin Luo, Guigao Guo","doi":"10.1016/j.intimp.2026.117564","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117564","url":null,"abstract":"<p><strong>Background: </strong>Ischemic heart disease (IHD) still works as the leading cause of mortality through the world. Endoplasmic reticulum (ER) stress is a key player in the pathogenesis of IHD. However, the potential mechanisms and key regulatory factors remain not fully clear.</p><p><strong>Methods: </strong>In our research, single-cell RNA sequencing data were integrated with summary-data-based Mendelian randomization (SMR) and colocalization analyses, aimed at systematically recognizing ER stress-related genes associated with IHD and to evaluate genetically predicted associations with IHD. The selected candidate was subsequently examined using single-cell expression analysis and in vitro experiments involving pro-inflammatory THP-1 macrophage-like cells and AC16 cardiomyocytes. Cytokine expression in macrophages was assessed by quantitative PCR, whereas cytokine concentrations in OGD-conditioned medium were measured by enzyme-linked immunosorbent assay. Recipient-cell ER-stress and ferroptosis-associated responses were evaluated using molecular, biochemical and pharmacological rescue assays.</p><p><strong>Results: </strong>A total of 2564 genes associated with both IHD and ER stress were identified, enriched in pathways related to oxidative stress, protein folding, and apoptotic signalling. Integrative SMR, colocalization and Mendelian randomization analyses identified a genetically predicted inverse association between TXNDC17 expression and IHD risk, thereby prioritizing TXNDC17 for subsequent functional investigation. Pseudotemporal analysis revealed a dynamic alteration in TXNDC17 expression during myeloid cell development, with an initial increase followed by a subsequent decrease. Experimental validation revealed that TXNDC17 was highly expressed in myeloid cells and that its knockdown in macrophages aggravated OGD-induced injury, increased pro-inflammatory cytokine production and release, and increased apoptosis-associated injury. OGD-conditioned medium from TXNDC17-silenced macrophages further promoted ER stress- and ferroptosis-associated injury in cardiomyocytes.</p><p><strong>Conclusions: </strong>Genetically predicted TXNDC17 expression was inversely associated with IHD risk. Functional experiments further implicated macrophage TXNDC17 in regulating inflammatory conditioned-medium-mediated cardiomyocyte injury, although its causal relevance to IHD in vivo remains to be established.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"190 ","pages":"117564"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AAV-mediated Siglecf elimination on TAMs reverses TMZ therapy-induced T cell dysfunction in glioblastoma.","authors":"Zhenkun Yang, Jie Li, Daxing Xu, Qianqian Xu, Jiao Meng, Jingjing Wang, Bo Zhang, Juncheng Dai, Yi Zhang, Zhening Pu, Ying Yin","doi":"10.1016/j.intimp.2026.117540","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117540","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most aggressive primary tumor of the brain, characterized by extensive intratumor heterogeneity, and exhibits inevitable recurrence despite conventional therapy. This study investigates the immunosuppressive mechanisms underlying GBM recurrence following temozolomide (TMZ) therapy, with a specific focus on macrophage-associated pathways driving immune evasion. By integrating single-cell RNA sequencing and mass cytometry time-of-flight analyses in orthotopic mouse GBM models, we revealed extensive transcriptional and phenotypic remodeling of the tumor microenvironment after TMZ treatment, including reduced malignant cell proliferation, activation of cytokine-mediated signaling, pronounced T-cell exhaustion, and a shift of tumor-associated macrophages (TAMs) toward immunosuppressive sialic acid-binding Ig-like lectin F (Siglec-F, encoded by Siglecf) positive subsets. Functional validation demonstrated that expression of Siglec-F inhibited macrophage phagocytosis and enhanced immunosuppression, whereas Siglecf-targeted intervention using adeno-associated virus (AAV) restored T-cell activation and improved antitumor efficacy. Analyses of human GBM datasets confirmed the enrichment of SIGLEC5⁺ (human homolog of murine Siglecf) TAMs in recurrent tumors, correlating with adverse prognosis. Collectively, our findings suggest a TMZ-induced immunosuppressive reprogramming of GBM microenvironment and implicate Siglec-F/SIGLEC5⁺ TAMs as potential mediators of immune escape and promising therapeutic targets to overcome chemoresistance.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"191 Pt 1","pages":"117540"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cells inhibit cigarette smoke extract-induced dendritic cells activation and alleviate chronic obstructive pulmonary disease.","authors":"Ronghao Zhang, Xiaoyu Wang, Xing Zhang, Liying Zhao, Xinran Shan, Jie Liu, Jun Ma, Xuejun Guo, Yue Zhang","doi":"10.1016/j.intimp.2026.117568","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117568","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a common lung disease; however, these is a need for new therapeutic drugs. Herein, we prepared cigarette smoke extract (CSE)-induced dendritic cells (DCs) activation, and investigated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) on DCs. We found that BMSCs inhibited CSE induced DCs maturation. In addition, in COPD mice, BMSCs and umbilical cord blood-derived mesenchymal stem cells (UCBSCs) decreased percentage of DCs and macrophages in lungs. Furthermore, BMSCs and UCBSCs inhibited the mRNA level of inflammatory cytokines, such as TNFα, IL-6, IL-1β and iNOS via qRT-PCR. Nr4a family members were upregulated in COPD mice, and BMSC and UCBSC treatment inhibited Nr4a1, Nr4a2 and Nr4a3 expression via qRT-PCR, immunohistochemistry and Western blot. In addition, BMSCs and UCBSCs inhibited inflammation in colon of mice with CODP and regulated the gut microbiota using 16S rRNA gene sequencing. Collectively, our findings reveal that Nr4a family members are involved in the BMSCs-and UCBSCs-amelioration of COPD.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"191 Pt 1","pages":"117568"},"PeriodicalIF":5.6,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mincle exacerbates neuroinflammation and dopaminergic neurodegeneration via synergistic crosstalk with TLR4.","authors":"Wei Zhang, Haiyang Fu, Weiping Shi, Feng Xue","doi":"10.1016/j.intimp.2026.117562","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117562","url":null,"abstract":"<p><p>Microglial activation and subsequent neuroinflammation are critically implicated in the pathogenesis and progression of Parkinson's disease (PD). Macrophage-inducible C-type lectin (Mincle) is a pivotal pattern recognition receptor that participates in the regulation of innate immune responses. Nevertheless, the functional role of Mincle in mediating dopaminergic neuronal injury in PD remains poorly defined. In the present study, we observed a marked upregulation of Mincle expression in microglia in PD mouse models. Pharmacological inhibition of Mincle via Anti-Mincle antibody treatment effectively alleviated LPS-triggered dopaminergic neuronal loss in the SN and rescued motor behavioral impairments in mice. Additionally, Mincle blockade promoted microglial phenotypic transformation, driving a shift from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Mechanistically, pharmacological blockade of either TLR4 or NF-κB signaling abrogated LPS-induced Mincle upregulation. Chromatin immunoprecipitation (ChIP) assays further confirmed that the NF-κB/P65 subunit directly binds to the promoter region of the Mincle, verifying that the TLR4/NF-κB signaling serves as a critical upstream regulatory pathway for Mincle expression. Notably, this study provides the first in vivo evidence that Mincle activation by a Mincle-specific agonist trehalose-6,6-dibehenate (TDB) induces robust dopaminergic neurotoxicity and motor dysfunction in C57BL/6 J mice, accompanied by significant elevations in the expression of the pro-inflammatory and microglial activation markers iNOS and CD68. Collectively, our findings demonstrate that synergistic crosstalk between the Mincle-Syk signaling cascade and the TLR4/NF-κB pathway sustains the pro-inflammatory M1 microglial phenotype, thereby triggering progressive dopaminergic neuronal damage in the SN. This study uncovers a previously unrecognized pathogenic role of Mincle in neuroinflammation-mediated neurodegeneration, highlighting Mincle as a promising novel therapeutic target for PD intervention.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"191 Pt 1","pages":"117562"},"PeriodicalIF":5.6,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agrimonolide induces endoplasmic reticulum stress-driven immunogenic cell death in ovarian cancer by reducing PFKFB3 expression.","authors":"Lufang Wang, Yixiong Chen, Guiju Tang","doi":"10.1016/j.intimp.2026.117544","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117544","url":null,"abstract":"<p><strong>Background: </strong>Endoplasmic reticulum stress (ERS)-driven immunogenic cell death (ICD) has been proven to be a highly promising approach for cancer treatment. Agrimonolide (Agr) has been confirmed to play an anti-tumor role in ovarian cancer (OC). However, whether Agr inhibits OC progression by regulating ERS-driven ICD remains unknown.</p><p><strong>Methods: </strong>OC cells were treated with different concentrations of Agr and co-cultured with dendritic cells (DC). Cell proliferation was measured with CCK8 and colony formation assay. Flow cytometry was used to test cell apoptosis, calreticulin level, and DC maturation. The levels of ERS-related markers, DC activation markers and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) were examined using western blot or qRT-PCR. A mouse tumor model was constructed to evaluate the effect of Agr on OC tumor growth.</p><p><strong>Results: </strong>Agr repressed OC cell proliferation, enhanced apoptosis, induced ERS-driven ICD and DC activation. Furthermore, Agr inhibited OC tumor growth, induced ERS-driven ICD, and activated the anti-tumor immune response. In terms of mechanism, Agr targeted PFKFB3 to reduce its mRNA stability and protein expression. In addition, Agr suppressed OC cell growth by inducing ERS-driven ICD via downregulating PFKFB3.</p><p><strong>Conclusion: </strong>Agr induced ERS-driven ICD to inhibit OC cell growth and tumorigenesis by repressing PFKFB3 expression, providing a potential molecular mechanism for understanding the anti-tumor effects of Agr in OC.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"191 Pt 1","pages":"117544"},"PeriodicalIF":5.6,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"HO-1 alleviates lipopolysaccharide-induced acute lung injury in mice by downregulating TFE3 expression and nuclear translocation and suppressing Golgi stress response\" [Int. Immunopharmacol. 186 (2026) 117103].","authors":"Xiangyun Li, Shihan Du, Yimeng Wang, Yan Huang, Ye Zhang, Chengyu Li, Zhaoguo Liu, Shuan Dong, Ya Wu, Shasha Liu, Jia Shi, Yuan Zhang, Jianbo Yu","doi":"10.1016/j.intimp.2026.117492","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117492","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"117492"},"PeriodicalIF":5.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Calreticulin-driven immunogenic cell death promotes osteoclast differentiation and osteoarthritis progression via the LRP1/Rac1 signaling\" [Int. Immunopharmacol. 163 (2025) 115277].","authors":"Qi Ma, Zhibin Lan, Yang Yang, Rui Sun, Di Xue, Xue Lin, Yajing Su, Long Ma, Zhijun Hu, Gang Wu, Xiaoxin He, Kuanmin Tian, Qunhua Jin","doi":"10.1016/j.intimp.2026.117491","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117491","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"117491"},"PeriodicalIF":5.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}