Inflammation最新文献

{"title":"Piezo1-Induced Nasal Epithelial Barrier Dysfunction in Allergic Rhinitis.","authors":"Shengyang Liu, Jianhua Wu, Linghui Meng, Yuan Liu, Jinzhuang Yu, Jing Yue, Dingqian Hao, Peng Yu, YuZhu Wan, Ping Li, Peng Jin, Li Shi","doi":"10.1007/s10753-024-02234-9","DOIUrl":"10.1007/s10753-024-02234-9","url":null,"abstract":"<p><p>This study aimed to investigate the role of Piezo1 in nasal epithelial barrier dysfunction in allergic rhinitis (AR) using both in vitro and in vivo experimental methods. A total of 79 human nasal mucosal samples were collected, including 43 from AR patients and 36 from healthy controls. Additionally, 12 BALB/c mice were used for the in vivo experiments. Human nasal epithelial cells (HNEpCs) were employed for the in vitro studies. In the in vivo study, mice were sensitized with ovalbumin (OVA) to induce AR. In the in vitro experiments, Piezo1 expression in HNEpCs was silenced using shRNA, followed by stimulation with IL-13. The expression of Piezo1, ERK1/2, and tight junctions (TJs) components (including ZO-1, Occludin, and Claudin-1) was assessed using quantitative RT-PCR, immunofluorescence, and Western blotting. Statistical analyses included paired Student's t-test and one-way ANOVA. Piezo1 expression was significantly elevated in both AR patients and OVA-induced AR mice, while TJs components were significantly reduced (p < 0.05). Knockdown of Piezo1 in HNEpCs restored the levels of TJs and improved barrier integrity. A negative correlation between Piezo1 and ERK1/2 expression was observed. Piezo1 plays a crucial role in nasal epithelial barrier dysfunction in AR by modulating TJs and the ERK1/2 pathway. These findings suggest that Piezo1 may serve as a potential therapeutic target for AR.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2824-2836"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964626","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":"Nrg4 Secreted by Brown Adipose Tissue Suppresses Ferroptosis of Sepsis-Induced Liver Injury.","authors":"Linqi Feng, Jun Cui, Wenlong Chen, Lei Zhu, Panpan Li, Haitao Zhou, Yang Sun, Wei Yi","doi":"10.1007/s10753-024-02230-z","DOIUrl":"10.1007/s10753-024-02230-z","url":null,"abstract":"<p><p>Sepsis is a leading cause of death, with the liver being particularly vulnerable to sepsis-related injuries. This damage significantly contributes to disease progression, underscoring the need for new treatments. Brown adipose tissue (BAT) secretes various cytokines, including neuregulin 4 (Nrg4), which plays a protective role in hepatic glucose and lipid metabolism. Ferroptosis, a key type of cell death in sepsis-induced liver injury, has recently gained attention. This study aimed to investigate how BAT-secreted cytokines alleviate liver ferroptosis in sepsis. Septic liver injury was induced in the control and BAT group using cecal ligation and puncture (CLP) and lipopolysaccharide injections. BAT removal worsened ferroptosis; in contrast, CL316243 activation reduced it. These findings suggest that Nrg4 secretion following BAT activation protects the liver during sepsis by inhibiting ferroptosis. Future therapies targeting BAT activation and Nrg4 could potentially mitigate sepsis-induced liver damage, offering new insights into treatment strategies.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2783-2801"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432940","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":"Combined Bulk and Single-Cell Transcriptomic Analysis to Reveal the Potential Influences of Intestinal Inflammatory Disease on Multiple Sclerosis.","authors":"Zhu Xu, Junyu Zhu, Zhuo Ma, Dan Zhen, Zindan Gao","doi":"10.1007/s10753-024-02195-z","DOIUrl":"10.1007/s10753-024-02195-z","url":null,"abstract":"<p><p>Multiple sclerosis (MS) and inflammatory bowel disease (IBD) are both autoimmune disorders caused by dysregulated immune responses. Still, there is a growing awareness of the comorbidity between MS and IBD. However, the shared pathophysiological mechanisms between these two diseases are still lacking. RNA sequencing datasets (GSE126124, GSE9686, GSE36807, GSE21942) were analyzed to identify the shared differential expressed genes (DEGs) for IBD and experimental allergic encephalomyelitis (EAE). Other datasets (GSE17048, GSE75214, and GSE16879) were downloaded for further verification and analysis. Shared pathways and regulatory networks were explored based on these DEGs. The single-cell transcriptome of central nervous system (CNS) immune cells sequenced from EAE brains and the public datasets of IBD (PRJCA003980) were analyzed for the immune characteristics of the shared DEGs. Mass cytometry by time-of-flight (CyTOF) of peripheral blood mononuclear cells (PBMCs) was performed for the systematic immune response in the EAE model. Machine learning algorithms were also used to identify the diagnostic biomarkers of MS. We identified 74 common DEGs from the selected RNA sequencing datasets, and single-cell RNA data of the intestinal tissues of IBD patients showed that 56 of 74 DEGs were highly enriched in IL1B⁺ macrophages. These 56 DEGs, defined as inflammation-related DEGs (IRGs), were also highly expressed in pro-inflammatory macrophages of EAE mice and MS patients. The abundance of systematic CD14⁺ monocytes was validated by CyTOF data. These IRGs were highly enriched in immune response, NOD-like receptor signaling pathway, IL-18 signaling pathway, and other related pathways. In addition, 'AddModuleScore_UCell' analysis further validated that these IRGs (such as IL1B, S100A8, and other inflammatory factors) are highly expressed mainly in pro-inflammatory macrophages, which play an essential role in pro-inflammatory activation in IBD and multiple sclerosis, such as IL-17 signaling pathway, NF-kappa B signaling pathway, and TNF signaling pathway. Finally, suppressors of cytokine signaling 3(SOCS3) and formyl peptide receptor 2(FPR2) were identified as potential biomarkers by machine learning. Two genes were highly expressed in pro-inflammatory macrophages of IBD and MS disease compared to control, and other datasets and experiments further revealed that SOCS3 and FPR2 were highly expressed in IBD and EAE samples. These shared IRGs, which encode inflammatory cytokines, exhibit high expression levels in inflammatory macrophages in IBD and may play a significant role in the inflammatory cytokine storm in MS patients. Two potential biomarkers, SOCS3 and FPR2, were screened out with great diagnostic value for MS and IBD.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2367-2386"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828437","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":"Bacterial Extracellular Vesicles as Potential Promoting Factors for Oral Lichen Planus Pathogenesis.","authors":"Yu Gyung Kim, Hyo-Jin Song, Hyeon Ji Kim, Bo Kyung Joo, Jin-Hwa Cho, Won Jung, Sungil Jang, Song-Yi Choi, Heon-Jin Lee, Jin-Seok Byun, Do-Yeon Kim","doi":"10.1007/s10753-024-02146-8","DOIUrl":"10.1007/s10753-024-02146-8","url":null,"abstract":"<p><p>Oral lichen planus (OLP) is a chronic inflammatory disease characterized by an intensive infiltration of cytotoxic T cells, which causes keratinocyte death. Abnormal changes within keratinocytes might be critical for OLP onset and progression, but the pathogenic mechanism of OLP is still uncertain. The human oral microbiota, consisting of approximately 50-100 billion bacterial entities, encompasses around 200 dominant bacterial species. These bacteria continuously produce and release extracellular vesicles (EVs), which play a significant role in host-microbe interactions. However, the impact of these bacterial EVs on the progression of OLP has not been fully elucidated. In this study, through comprehensive database analysis and experimental validation, we observed that OLP lesions exhibit elevated inflammatory signatures and significantly increased phosphorylation of STAT3 compared to non-OLP tissues. Notably, EVs derived from key periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were shown to induce an inflammatory response and activate STAT3 signaling pathways, closely mirroring the pathophysiological features observed in OLP. These results underscore the potential role of bacterial EVs in the pathogenesis of OLP and highlight STAT3 as a critical mediator in this process.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1660-1670"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286191","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":"Role for IRAK-4 and p38 in Neutrophil Signaling in Response to Bacterial Lipoproteins from Staphylococcus aureus.","authors":"Jessica S Hook, Austin D Matheis, Jeffrey S Kavanaugh, Alexander R Horswill, Jessica G Moreland","doi":"10.1007/s10753-024-02147-7","DOIUrl":"10.1007/s10753-024-02147-7","url":null,"abstract":"<p><p>Neutrophils, polymorphonuclear leukocytes (PMN), express numerous pattern recognition receptors, including TLRs, capable of recognizing a wide variety of pathogens. Receptor engagement initiates a cascade of PMN responses with some occurring in seconds, and some requiring de novo protein synthesis over the course of many hours. Although numerous species of bacteria and bacterial products have been shown to activate PMN via TLRs, the signaling intermediates required for distinct PMN responses have not been well-defined in human PMN. Given the potential for host tissue damage by overexuberant PMN activity, a better understanding of neutrophil signaling is needed to generate effective therapies. We hypothesized that PMN responses to a lipoprotein-containing cell membrane preparation from methicillin-resistant S. aureus (MRSA-CMP) would activate signaling via IRAK4 and p38, with potentially distinct pathways for early vs. late responses. Using human PMN we investigated MRSA-CMP-elicited reactive oxygen species (ROS) production, elastase activity, NET formation, IL-8 production, and the role of IRAK4 and p38 activation. MRSA-CMP elicited ROS in a concentration and lipoprotein-dependent manner. MRSA-CMP elicited phosphorylation of p38 MAPK, and MRSA-CMP-elicited ROS production was partially dependent on p38 MAPK and IRAK4 activation. Inhibition of IRAK4 resulted in a reduction of p38 phosphorylation. MRSA-CMP-elicited elastase activity and NET formation was partially dependent on p38 MAPK activation, but independent of IRAK4 activation. MRSA-CMP-elicited IL-8 production required both p38 and IRAK4 activation. In conclusion, MRSA-CMP elicits PMN responses via distinct signaling pathways. There is potential to target components of the neutrophil inflammatory response without compromising critical pathogen-specific immune functions.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1704-1715"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286193","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":"Metformin Attenuates Vocal Fold Fibrosis via AMPK Signaling.","authors":"Jie Cai, Lucheng Fang, Peng Zhou, Jianghao Wu, Yuliang Song, Aikebaier Tuohuti, Yuechen Sun, Xiong Chen","doi":"10.1007/s10753-024-02165-5","DOIUrl":"10.1007/s10753-024-02165-5","url":null,"abstract":"<p><p>Vocal fold fibrosis is a challenging condition with no clear consensus on effective treatment methods. Given the demonstrated efficacy of metformin in treating various fibrotic diseases, we hypothesized that metformin could reduce vocal fold fibrosis via the AMPK signaling pathway. In our study, we induced vocal fold injury in rabbits and administered metformin intraperitoneally at a dose of 250 mg/kg two weeks post-injury. Four weeks after the injury, vocal folds were excised and analyzed for fibrosis using Masson's trichrome staining, immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR), and Western blotting. In vitro, vocal fold fibroblasts treated with metformin (10 μM) ± TGF-β1 (10 ng/mL) were utilized to assess metformin's antifibrotic effects, with Compound C (10 μM) employed to inhibit AMPK signaling. Our results demonstrate that metformin significantly improved the structural integrity of the vocal fold lamina, reduced collagen deposition, and decreased the expression levels of COL1A1 and α-SMA. Furthermore, metformin activated the AMPK signaling pathway in vocal fold fibroblasts, resulting in decreased expression of COL1A1, α-SMA, TGF-β, Smad2, and Smad3. These findings suggest that metformin attenuates vocal fold fibrosis by modulating the AMPK signaling pathway, providing a foundation for developing new therapeutic options for vocal fold fibrosis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1929-1939"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499559","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":"Bifidobacterium longum Metabolite Indole-3-Carboxaldehyde Blocks HDAC3 and Inhibits Macrophage NLRP3 Inflammasome Activation in Intestinal Ischemia/Reperfusion Injury.","authors":"Yan Miao, Mian Wang, Hao Sun, Yujie Zhang, Wei Zhou, Wanli Yang, Lili Duan, Liaoran Niu, Zhenshun Li, Junfeng Chen, Yiding Li, Aqiang Fan, Qibin Xie, Siyu Wei, Han Bai, Chenyang Wang, Qian Chen, Xiangjie Wang, Yunlong Li, Jinqiang Liu, Yu Han, Daiming Fan, Liu Hong","doi":"10.1007/s10753-024-02211-2","DOIUrl":"10.1007/s10753-024-02211-2","url":null,"abstract":"<p><p>Indole-3-carboxaldehyde (3-IAld), a tryptophan metabolite derived from gut microbiota, has been reported to protect the intestine against radiation injury. This study aimed to clarify the role of Bifidobacterium longum (B. longum) and its metabolite indole-3-carboxaldehyde (3-IAld) in the pathophysiology of intestinal ischemia/reperfusion (II/R) injury. Superior mesenteric artery occlusion and reperfusion were performed to establish II/R mice, and pathological injury in II/R mice was evaluated. II/R mice showed impaired gut microbiota diversity and reduced abundance of B. longum in the intestines. Transplantation of B. longum mitigated II/R injury by protecting the integrity of the intestinal barrier and reducing inflammatory response. The 3-IAld level increased after transplantation of B. longum, and 3-IAld treatment inhibited the inflammatory response of bone marrow-derived macrophages (BMDM). Histone deacetylase 3 (HDAC3) was a target of 3-IAld, and HDAC3 was translocated to mitochondria to promote mitochondrial fatty acid oxidation (FAO) during macrophage inflammasome formation. HDAC3 overexpression promoted the formation of macrophage inflammasomes in intestinal tissues. Overall, this study confirmed the beneficial effects of B. longum in combating II/R injury through HDAC3-mediated control of mitochondrial FAO and macrophage inflammasome formation via 3-IAld.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2572-2587"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812302","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":"IRF-1 Regulates Mitochondrial Respiration and Intrinsic Apoptosis Under Metabolic Stress through ATP Synthase Ancillary Factor TMEM70.","authors":"ChongXiu Sun, Haotian Sun, Jiahao Wei, Xing Fan, Scott I Simon, Anthony G Passerini","doi":"10.1007/s10753-024-02209-w","DOIUrl":"10.1007/s10753-024-02209-w","url":null,"abstract":"<p><p>Mitochondrial dysfunction, which can be caused by metabolic stressors such as oxidized low-density lipoprotein (oxLDL), sensitizes the endothelium to pathological changes. The transcription factor interferon regulatory factor 1 (IRF-1) is a master regulator of inflammation, previously shown to promote oxLDL-induced inflammatory pyroptosis in human aortic endothelial cells (HAEC). However, a presumed role for IRF-1 in regulating the intrinsic apoptotic pathway in response to metabolic stress has not been demonstrated. Here targeted deletion of IRF-1 by siRNA in HAEC aggravated oxLDL-induced, mitochondria-mediated intrinsic apoptosis, as evidenced by increased Caspase-3 and Caspase-9 activation, and chromosomal DNA breakage. The increased apoptosis was concomitant with accumulation of mitochondrial ROS, decrease in intracellular ATP production and respiratory oxygen consumption, and abnormal mitochondrial structure. RNA profiling of endothelial cells isolated from wild type and Irf1 knockout mice, followed by quantitative PCR, luciferase activity assay and chromatin immunoprecipitation (ChIP), revealed that IRF-1 directly regulated the expression of transmembrane protein 70 (TMEM70), an ancillary factor required for the assembly of ATP synthase and conversion of an electrochemical gradient to ATP synthesis. Mirroring the effect of IRF1 knockdown, depletion of TMEM70 in HAEC resulted in impaired mitochondrial function and enhanced cell apoptosis. In contrast, overexpression of TMEM70 rescued ATP biosynthesis and suppressed apoptosis in oxLDL-treated, IRF-1-deficient HAEC. These results reveal a novel homeostatic role for IRF-1 in the regulation of mitochondrial function and associated stress-induced apoptosis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2548-2562"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785404","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":"NG-497 Alleviates Microglia-Mediated Neuroinflammation in a MTNR1A-Dependent Manner.","authors":"Qi Li, Pinyi Liu, Xuan Zhu, Chao Zhou, Yujie Hu, Shiying Cao, Huiya Li, Xinxin Zou, Shenghan Gao, Xiang Cao, Xinyu Bao, Yun Xu, Jingwei Li","doi":"10.1007/s10753-024-02218-9","DOIUrl":"10.1007/s10753-024-02218-9","url":null,"abstract":"<p><p>Microglia-mediated neuroinflammation plays a crucial role in multiple neurological diseases. We have previously found that Atglistatin, the mouse Adipose Triglyceride Lipase (ATGL) inhibitor, could promote lipid droplets (LDs) accumulation and suppress LPS-induced neuroinflammation in mouse microglia. However, Atglistatin was species-selective, which limited its use in clinical settings. Here, we found that NG-497, a previously identified human ATGL inhibitor, significantly increased LDs accumulation and inhibited LPS-induced pro-inflammatory responses in human microglia. Moreover, NG-497 also protected human neurons against neurotoxic cytokines in a humanized in vitro model of neuroinflammation. However, the anti-inflammatory capacity of NG-497 was independent of its effect on ATGL. Instead, we revealed that NG-497 alleviated microglia-mediated neuroinflammation through elevating the protein level of melatonin receptor 1A (MTNR1A). Therefore, in this study, we uncovered a novel MTNR1A-targeting compound, which exhibited anti-inflammatory and neuroprotective effect, highlighting its potential in the treatment of neuroinflammation. Moreover, the MTNRs agonist, Ramelteon, exerts comparable anti-inflammation effects with NG-497.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2663-2676"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921581","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":"Exosomes Derived from Endoplasmic Reticulum Stressed Hepatocellular Carcinoma Cells Enhance the Antitumor Immunity of Dendritic Cells.","authors":"Ju Zhang, Jiatao Liu, Jing Ni, Xiao Lin, Lulu Fan, Guoping Sun","doi":"10.1007/s10753-024-02214-z","DOIUrl":"10.1007/s10753-024-02214-z","url":null,"abstract":"<p><p>Endoplasmic reticulum stress (ERs) is implicated in antitumor immunity. However, the exact role of ERs in mediating the effects of dendritic cells (DCs) is not unclear. In this study, we explored the role of exosomes derived from ER-stressed hepatocellular carcinoma (HCC) cells in the antitumor effects of DCs and the precise underlying mechanism. We found that ER-stressed HCC cells secreted more exosomes (EXO-TM) than those without ER stress (EXO-CON) and that exosomes were effectively taken up by DCs. EXO-TM significantly promoted DCs maturation, as demonstrated by the increased expression of HLA-ABC, CD83, CD80, CD86, and pro-inflammatory cytokines and the decreased expression of IL-10. Moreover, EXO-TM pulsed DCs (DC_EXO-TM) significantly enhanced T lymphocyte-mediated lysis against several types of tumor cells by promoting the proliferation of CD3⁺CD8⁺ T cells and increasing the expression of INF-γ both in vitro and in vivo. Mechanistically, we found that heat shock protein (HSP) 90 was more significantly enriched in EXO-TM than in EXO-CON cells, and the knockdown of HSP90 remarkably reversed EXO-TM-mediated DC activation. Our results suggest that exosomes derived from ER-stressed HCC cells could enhance the antitumor effect of DC-mediated T lymphocytes, which may be related to the large amount of HSP90 carried in the exosomes. Therefore, regulating the HSP90 carrying capacity of tumor exosomes may be an effective immunotherapy strategy.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2613-2627"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876919","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}