Molecular immunology最新文献

{"title":"Plasma secretory protein genes in hepatocellular carcinoma and heart failure: Comorbidity and biological function exploration","authors":"Lizhi Cao ,&nbsp;Xiaoying Wang ,&nbsp;Zhongping Ning ,&nbsp;Fandi Xie ,&nbsp;Xiaodan Li ,&nbsp;Yongting Chen ,&nbsp;Qian Geng ,&nbsp;Junchi Liu ,&nbsp;Qian Zhu ,&nbsp;Linlin Ma ,&nbsp;Yanfei Li","doi":"10.1016/j.molimm.2025.10.009","DOIUrl":"10.1016/j.molimm.2025.10.009","url":null,"abstract":"<div><h3>Background</h3><div>This research aimed to elucidate the roles of plasma secretory protein genes in mediating the comorbid effects between hepatocellular carcinoma (HCC) and heart failure (HF).</div></div><div><h3>Methods</h3><div>A comprehensive analysis utilizing Weighted Gene Co-expression Network Analysis (WGCNA), differential expression analysis, and advanced deep learning techniques was conducted to identify three plasma-secreted protein genes (Ficolin-3: FCN3, Fibroblast Activation Protein: FAP, High Mobility Group Box 2: HMGB2) as key players in the comorbid interplay between HCC and HF.</div></div><div><h3>Results</h3><div>Validation experiments confirmed the significant biological functions of these genes in disease pathogenesis. Additionally, dexamethasone and catechins were identified as promising candidates for pharmacological intervention in the prevention of HCC and HF.</div></div><div><h3>Conclusion</h3><div>These findings unveil potential mechanistic pathways of comorbidity between HCC and HF, providing novel biological markers and therapeutic targets for the prognostic evaluation and treatment of these conditions, with substantial implications for refining clinical diagnosis and therapeutic strategies.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 45-61"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NSUN2-mediated m⁵C methylation of HSPB1 mRNA suppresses inflammation and ferroptosis in ischemic stroke via activating the NRF2/HO-1/NQO-1 pathway","authors":"Genshan Gao ,&nbsp;Baixiang Zhang ,&nbsp;Nannuan Liu ,&nbsp;Nan Liu ,&nbsp;Yixian Zhang ,&nbsp;Houwei Du","doi":"10.1016/j.molimm.2025.11.005","DOIUrl":"10.1016/j.molimm.2025.11.005","url":null,"abstract":"<div><div>Ischemic stroke (IS), a leading cause of disability and mortality, is characterized by cerebral ischemia-reperfusion injury, inflammation, and ferroptosis. RNA 5-methylcytosine (m5C) modification is a dynamic epigenetic mark involved in various pathological processes, yet its role in IS remains unclear. This study aimed to investigate the role of m5C modification in IS and its underlying mechanisms. <em>In vitro</em>, human brain microvascular endothelial cells (HBMECs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R), while <em>in vivo</em>, a transient middle cerebral artery occlusion (tMCAO) mouse model was established. Reverse transcription-quantitative polymerase chain reaction was used to analyze the mRNA levels of NSUN2 and heat shock protein family B member 1 (HSPB1). The contents of pro-inflammatory cytokines and ferroptosis-related indicators were measured using enzyme-linked immunosorbent assay and commercial kits. The expression of nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone dehydrogenase 1 (NQO-1) pathway proteins was detected by Western blot. RNA immunoprecipitation and dual-luciferase reporter assays were performed to assess the interaction between NSUN2 and HSPB1. Results showed that NSUN2 was downregulated in OGD/R-treated HBMECs and tMCAO mice. Furthermore, NSUN2 overexpression mitigated OGD/R-induced inflammation and ferroptosis. Mechanistically, NSUN2 mediated m5C methylation at site 621 in HSPB1 mRNA, enhancing its stability. Knockdown of HSPB1 abolished the protective effects of NSUN2, exacerbating inflammation and ferroptosis in OGD/R-treated HBMECs. Further investigations revealed that the NSUN2/HSPB1 axis exerted its protective role by activating the NRF2/HO-1/NQO-1 pathway. Inhibition of this pathway reversed the beneficial effects of HSPB1 overexpression. In tMCAO mice, NSUN2 overexpression reduced cerebral infarct volume, improved antioxidant capacity, and activated the NRF2/HO-1/NQO-1 pathway. In conclusion, NSUN2-mediated m⁵C methylation stabilized HSPB1 and activated the NRF2/HO-1/NQO-1 pathway, thereby mitigating inflammation and ferroptosis in IS. Targeting the NSUN2/HSPB1 axis may represent a novel therapeutic strategy for IS.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 131-141"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hdh-GSK in Pacific abalone: Insights into its roles in metamorphosis, stress response, and innate immunity","authors":"Md Abu Hanif ,&nbsp;Doo Hyun Cho ,&nbsp;Soo Cheol Kim ,&nbsp;Ji Do Han ,&nbsp;Won Kyo Lee ,&nbsp;Kang Hee Kho","doi":"10.1016/j.molimm.2025.11.003","DOIUrl":"10.1016/j.molimm.2025.11.003","url":null,"abstract":"<div><div>Glycogen synthase kinases (GSKs) regulate key physiological processes in eukaryotes, but their role in Pacific abalone remains unexplored. In this study, the GSK gene was identified and characterized from Pacific abalone (<em>Haliotis discus hannai</em>), and the expression was analyzed to investigate the role of GSK in early development, stress response, and innate immunity. The <em>Hdh-</em>GSK cDNA sequence comprised 1436 bp, with a 456 bp open reading frame (ORF) that encodes 151 deduced amino acid residues. Structurally, the <em>Hdh</em>-GSK protein contains a binding site for the Batabulin ligand (an anti-tumor agent). <em>Hdh-</em>GSK was significantly expressed in the digestive gland, a prime immune organ in aquatic organisms. Notably, higher expression during embryonic and larval development suggests the <em>Hdh-</em>GSK performs a dynamic role in the early development of Pacific abalone. Furthermore, <em>Hdh-</em>GSK expression was significantly higher in individuals exhibiting average and rapid growth than those with stunted or minimal growth. Further, <em>Hdh-</em>GSK expression was upregulated during starvation. Short-term heat stress (6–12 h) upregulated its expression, while prolonged stress led to downregulation, likely linked to ROS production. Cd-toxicity downregulated <em>Hdh-</em>GSK expression in a dose- and time-dependent manner. Immune challenges with <em>Vibrio parahaemolyticus</em>, LPS and poly(I:C) significantly downregulated <em>Hdh</em>-GSK expression (aside from an initial slight increase with bacteria and LPS), suggesting its role in anti-inflammatory responses. Overall, this study’s findings suggest that <em>Hdh-</em>GSK may be a key candidate gene for elucidating molecular processes during early development, growth, and innate immunity in Pacific abalone.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 154-167"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human cord blood mononuclear cells alleviate intestinal inflammation and barrier dysfunction by regulating gut metabolites and Th17/Treg balance","authors":"Linmao Lyu ,&nbsp;Yanfei Ma ,&nbsp;Xuyan Sun ,&nbsp;Meng Luo ,&nbsp;Zhong Wang ,&nbsp;Lijun Fang ,&nbsp;Wenqiang Li ,&nbsp;Yuguo Chen ,&nbsp;Shize Liu ,&nbsp;Xiaopeng Jia","doi":"10.1016/j.molimm.2025.11.004","DOIUrl":"10.1016/j.molimm.2025.11.004","url":null,"abstract":"<div><h3>Background</h3><div>Cord blood mononuclear cells (CB–MNCs) are a potential alternative therapy for inflammatory bowel disease (IBD). Gut metabolites, T helper 17 (Th17) and regulatory T (Treg) cells are crucial for intestinal hemeostasis and recovery. However, the role of CB–MNCs in modulating IBD, gut metabolites and the Th17/Treg balance remains unclear.</div></div><div><h3>Methods</h3><div>In this study, dextran sodium sulfate (DSS) was used to induce acute colitis in male C57BL/6 J mice, followed by treatment with CB–MNCs, umbilical cord-derived mesenchymal stem cells (UC–MSCs), or mesalazine. The severity of colitis was assessed daily using the disease activity index (DAI), and feces were collected for metabolomic analysis. Upon sacrifice, the colons, mesenteric lymph nodes (MLNs) and spleens of the mice were preserved for further study.</div></div><div><h3>Results</h3><div>Our findings demonstrated that compared with UC–MSCs and mesalazine, CB–MNCs treatment had superior efficacy in improving clinical symptoms, tissue repair, promoting intestinal regeneration and integrity. While CB-MNCs were equivalent to UC–MSCs and mesalazine in terms of preserving colon length and anti-inflammatory activity. At the molecular level, CB-MNCs exhibited unique and powerful effects. CB-MNCs were found to significantly increase the abundance of cortisol, corticosterone, and several metabolites with anti-inflammatory and antioxidant activities in the feces of colitis mice. CB–MNCs were also more effective than UC–MSCs and mesalazine at maintaining Th17/Treg balance than UC–MSC and mesalazine in colitis mice.</div></div><div><h3>Conclusions</h3><div>The intravenous injection of CB-MNCs can alleviate intestinal inflammation and barrier dysfunction by modulating gut metabolites and the Th17/Treg balance. Therefore, CB-MNCs be a promising treatment for IBD.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 179-191"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Appropriate doses of ionizing radiation facilitate the proliferation and anti-tumor effects of γδ T cells through ERK and p38MAPK pathways in vitro","authors":"Lu-Lu Wang ,&nbsp;Yang Yang ,&nbsp;Yong-Bo Feng ,&nbsp;Han-Qing Zhao ,&nbsp;Qian Hong ,&nbsp;Fu-Xing Chen ,&nbsp;Ling Chen ,&nbsp;Lei-Qing Sun ,&nbsp;Xiao-Ting Lü ,&nbsp;Fei Sun ,&nbsp;Hui Feng ,&nbsp;Kai Chen ,&nbsp;Zeng-Hui Liu ,&nbsp;Li-Li Guo ,&nbsp;Zhong-Hai Zhou","doi":"10.1016/j.molimm.2025.10.013","DOIUrl":"10.1016/j.molimm.2025.10.013","url":null,"abstract":"<div><div>Low dose ionizing radiation exhibits immunomodulatory properties. However, the impact of various doses of ionizing radiation on the antitumor responses of γδ T cells remains uncertain. The present study aimed to investigate the effects of different doses of ionizing radiation on the proliferation, cytotoxicity and related molecular mechanisms of γδ T cells <em>in vitro</em>. Human γδ T cells were exposed to radiation by X-ray with different doses. CCK-8 assay was used to measure cell proliferation. Cytotoxic activity was detected using LDH release assay. Cytokines IFN-γ and TNF-α were measured by ELISA. Flow analysis was performed to determine the expressions of perforin, granzyme B and CD107a in/on γδ T cells. Protein expression of Bax, Bcl-2, p-ERK1/2, and p-p38MAPK in γδ T cells were evaluated by western blotting analysis. The results showed that γδ T cells of the 0.08 Gy dose group exhibited the most pronounced proliferation. The antitumor cytotoxicity of γδ T cells and the levels of IFN-γ and TNF-α in the 2 Gy and 4 Gy groups were higher than those in the control group. Accordingly, the expression of perforin, granzyme B, and CD107a in these two groups was upregulated significantly. Protein analysis indicated that in the 0.08 Gy group, the expression of Bcl-2 and p-ERK1/2 was significantly upregulated, whereas Bax was downregulated. In the 2.00 Gy group, the expression of p-p38MAPK was notably upregulated. These findings indicate that appropriate doses of ionizing radiation may promote γδ T cell proliferation through the ERK pathway, and enhance the cytotoxic activity of γδ T cells by upregulating critical cytokines production and the expression of cytotoxic molecules through the p38MAPK pathway.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 80-88"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the urokinase-type plasminogen activator system in viral infection and replication","authors":"Shihan Yang ,&nbsp;Jing Chen ,&nbsp;Xiaoshuang Shi ,&nbsp;Jiamin Wang ,&nbsp;Letian Li ,&nbsp;Shouwen Du ,&nbsp;Chang Li","doi":"10.1016/j.molimm.2025.10.012","DOIUrl":"10.1016/j.molimm.2025.10.012","url":null,"abstract":"<div><div>The urokinase-type plasminogen activator system (uPAs) consists of the urokinase-type plasminogen activator (uPA), its receptor (uPA receptor, uPAR) and the plasminogen activator inhibitor (PAI). Recent studies have revealed that, beyond its well-established roles in promoting fibrinolysis and degrading extracellular matrix (ECM) proteins—thereby regulating tissue repair and tumor metastasis—this system also plays a significant role in viral infections. Specifically, the uPAs modulates viral infection processes by regulating the expression and activity of uPA and uPAR, which are involved in inflammatory response modulation, immune cell migration, and the infiltration of inflammatory cells during tissue repair in the context of viral infections. In this review, we summarize the roles of uPAs in various viral infections, aiming to deepen our understanding of the contributions of each uPA component and provide insights into potential strategies for inhibiting viral infection processes.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 38-44"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145420402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZBTB16 promotes the transcription of glycolytic enzyme PFKFB2 to participate in fibrogenesis in septic lung injury","authors":"Zijian Tai,&nbsp;Chunting Wang","doi":"10.1016/j.molimm.2025.10.007","DOIUrl":"10.1016/j.molimm.2025.10.007","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis is a severe systemic inflammatory response syndrome that leads to acute lung injury (ALI), which subsequently progresses to lung fibrosis. This study aims to investigate the role of zinc finger and BTB domain containing 16 (ZBTB16), a transcription factor, in septic lung injury.</div></div><div><h3>Methods</h3><div>The expression of <em>Zbtb16</em> in the injured lung was evaluated using single-cell sequencing. The signaling pathways that can be regulated by <em>Zbtb16</em> were predicted using gene set enrichment analysis (GSEA). Then, the functions of <em>ZBTB16</em> and its potential molecular mechanism in fibrogenesis were explored in lipopolysaccharide (LPS)-induced ALI mice <em>in vivo</em> and LPS-induced MRC-5 cells and primary fibroblasts <em>in vitro</em>.</div></div><div><h3>Results</h3><div>Single-cell analysis showed that <em>Zbtb16</em> was overexpressed in the fibroblasts of the injured lung. GSEA found that <em>Zbtb16</em> might activate inflammatory response and glycolysis during lung injury. Silencing of <em>Zbtb16</em> relieved lung injury, decreased lung wet/dry weight and myeloperoxidase (MPO) activity, reduced the levels of lactate dehydrogenase (LDH), total protein, and neutrophil in the BALF, and inhibited fibrogenesis in septic ALI mice. In LPS-induced fibroblasts, silencing of <em>ZBTB16</em> suppressed the expression of inflammatory and fibrotic markers by inhibition of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2)-mediated glycolysis.</div></div><div><h3>Conclusion</h3><div>ZBTB16 promotes the transcription of glycolytic enzyme <em>PFKFB2</em> to participate in fibrogenesis in septic lung injury. Our study may offer a potentially promising target for the treatment of fibrogenesis in septic lung injury.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 12-26"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145384259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of AAV8-mediated IL-17RA extracellular domain gene delivery in an imiquimod-induced mouse model of psoriasis.","authors":"Huibin Xie ,&nbsp;Danping Li ,&nbsp;Yu Cao ,&nbsp;Yafeng Lv ,&nbsp;Chunyu Cao ,&nbsp;Hongyan Wu","doi":"10.1016/j.molimm.2025.11.001","DOIUrl":"10.1016/j.molimm.2025.11.001","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the therapeutic effects of adeno-associated virus serotype 8 (AAV8)–mediated delivery of the extracellular domain of IL-17RA (IL-17RA(ECD)) on imiquimod (IMQ)-induced psoriasiform dermatitis in mice.</div></div><div><h3>Methods</h3><div>A recombinant AAV core plasmid encoding murine IL-17RA–ECD (pAAV-mIL17RA(ECD)) was generated by gene synthesis and validated for secretory expression in HEK293T cells. The recombinant AAV8 vector carrying mIL-17RA(ECD) was produced by co-transfection of pAAV-mIL17RA(ECD), helper plasmid, and AAV8 capsid plasmid. In vivo, mice were divided into four groups (Vaseline, IMQ, Luciferase+IMQ, and IL-17RA+IMQ; n = 5 per group). On day 1, mice in the treatment group received subcutaneous injections of AAV8 vector encoding luciferase or mIL-17RA(ECD). Disease progression was monitored through body weight, photography, and PASI scoring. Histopathological changes were assessed by H&amp;E staining, and potential viral toxicity was examined in heart, liver, lung, and kidney tissues. Expression of inflammatory cytokines (TNF-α, IL-6, IL-1β，Defb4) at both mRNA and protein levels was measured by qPCR and ELISA.</div></div><div><h3>Results</h3><div>The recombinant plasmid pAAV-mIL17RA(ECD) was successfully constructed and demonstrated efficient secretory expression. AAV8-mediated mIL-17RA(ECD) expression significantly alleviated IMQ-induced psoriasiform dermatitis (P &lt; 0.05) and markedly suppressed the upregulation of inflammatory cytokines in skin and serum at both transcriptional and protein levels (P &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>AAV8-mediated IL-17RA(ECD) gene delivery effectively blocks cutaneous inflammation and attenuates inflammatory cytokines overexpression in an IMQ-induced mouse model of psoriasis, highlighting its therapeutic potential for chronic inflammatory skin diseases.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 89-97"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP18 inhibits CVB3-induced pyroptosis and fibrosis of mouse cardiomyocytes through the IRF7/NF-κB signaling pathway","authors":"Yan Zhang ,&nbsp;Lei Yang ,&nbsp;Huiting Mu ,&nbsp;Na Li ,&nbsp;Xuejia Wang ,&nbsp;Hualan Lei ,&nbsp;Mingjie Pang","doi":"10.1016/j.molimm.2025.10.014","DOIUrl":"10.1016/j.molimm.2025.10.014","url":null,"abstract":"<div><div>The pathogenesis of viral myocarditis (VMC) is closely related to microbial infections, among which Coxsackievirus B3 (CVB3) is a common pathogenic microorganism. The aim of this study is to explore the potential mechanism of USP18 in VMC caused by CVB3 infection. In this study, mice were injected intraperitoneally with 100 μL of CVB3 (10³ TCID50) to construct a VMC mouse model, and HL-1 cells were exposed to CVB3 to establish a VMC cell model. The expression of related genes and proteins was detected using RT<img>qPCR and Western blotting, and damage to cells and myocardial tissues was evaluated using ELISA, immunofluorescence, HE staining, etc. In this study, USP18 expression was upregulated in VMC- and CVB3-infected mice and HL-1 cells. USP18 knockdown not only promoted the expression of inflammatory factors (IL-18 and IL-1β), pyroptosis-related proteins (caspase-1, NLRP3, and GSDMD) and fibrosis-related proteins (α-SMA, Collagen I, and FN1) but also promoted the expression of myocardial injury markers (LDH, CK-MB, and cTnI) in vivo, aggravating the pathological damage to myocardial tissues. Moreover, USP18 overexpression inhibited CVB3-induced pyroptosis and fibrosis. Mechanistically, USP18 stabilizes IRF7 expression through deubiquitination, thereby promoting the binding of IRF7 to NF-κB, inhibiting the nuclear translocation of NF-κB, and ultimately inhibiting CVB3-induced pyroptosis and fibrosis and improving VMC. Our study suggests that upregulating USP18 expression may represent a new target for VMC treatment.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 62-72"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular pathways of radiation-induced lung damage: Effects of X-ray and Anti-PD-1 combination in a murine model","authors":"Chenglong Sun ,&nbsp;Yang Zhang ,&nbsp;Jinfeng Liu ,&nbsp;Nan Wei ,&nbsp;Fei Li ,&nbsp;Yuan Fang ,&nbsp;Yijun Li ,&nbsp;Songguo Li ,&nbsp;Xiaokai Ma ,&nbsp;Zhanggui Wang ,&nbsp;Xinyu Wang","doi":"10.1016/j.molimm.2025.10.015","DOIUrl":"10.1016/j.molimm.2025.10.015","url":null,"abstract":"<div><h3>Objective</h3><div>To clarify the impact of X-ray irradiation combined with PD-1 immune checkpoint inhibitor treatment on lung tissue in a mouse model of radiation-induced lung injury (RILI) and to investigate its underlying mechanisms.</div></div><div><h3>Methods</h3><div>A mouse RILI model was established by a single 16 Gy dose of whole-thorax irradiation. Mice were then treated with either an PD-1 inhibitor or a control. Lung injury and fibrosis were assessed by histological staining. Inflammatory cytokine levels (TNF-α, IL-6) were measured by ELISA. Macrophage M1 polarization was analyzed by flow cytometry and immunohistochemistry. The activation of the NF-κB signaling pathway was evaluated by Western blot.</div></div><div><h3>Results</h3><div>The lung injury indices in the group treated with irradiation combined with PD-1 inhibitor were higher than those in the irradiation-only group. Mechanistic studies found that PD-1 inhibitors promoted the activation of the NF-κB signaling pathway and simultaneously regulated macrophage polarization in lung tissue, promoting the differentiation of M1-type pro-inflammatory cells.</div></div><div><h3>Conclusion</h3><div>Whole-thorax X-ray irradiation combined with PD-1 inhibitors can exacerbate lung injury and pulmonary fibrosis in mice, and the mechanism of action may be through the regulation of NF-κB signaling pathway activation to promote macrophage polarization towards the M1 type.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 73-79"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}