Inflammation最新文献

{"title":"Expression and regulation network of BLNK in CP/CPPS in animal, cell model and clinical samples.","authors":"Peng Yu, Jiefu Huang, Xiang Gan, Yue Zhao, Siqin Liu, Dong Zhao, Hongtao Li, Weiyuan Liang, Zhouquan Li, Yanjun Tan, Wen Wei, Weijin Fu, Xiaoli Yang","doi":"10.1007/s10753-025-02353-x","DOIUrl":"https://doi.org/10.1007/s10753-025-02353-x","url":null,"abstract":"<p><p>B-cell linker (BLNK) is associated with the inflammatory process of certain diseases. However, no studies have explored the role of BLNK in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We performed transcriptome analysis of the rat model and found that BCR signaling pathway, especially the BLNK gene, is closely related to CP/CPPS. We detected the expression levels of BLNK gene or protein in CP/CPPS rat tissues, human expressed prostatic secretion (EPS), and cell models by qPCR, WB, and IHC. Subsequently, we silenced the BLNK gene in human prostatitis cell model. The cell cycle, and expression level of inflammatory factors were detected; the core pathway and interacting molecules of BLNK were revealed by mRNA/lncRNA sequencing, bioinformatics analysis and validation. Results showed that the BLNK gene or protein was significantly upregulated in the CP/CPPS rat tissues, human EPS, and cell model. Functionally, BLNK silencing inhibited the proliferation, promoted cell apoptosis and S phase arrest, and inhibited the expression of IL-1β, IL-6, and IL-8 at the human prostatitis cell model. Furthermore, the DEGs and DE-lncRNA induced by BLNK silencing were significantly enriched in the calcium signaling pathway, the BLNK has strongly interacted with EDNRB, FGF1, FGF2, and F2R. Moreover, in prostatitis group, all four genes are target genes of LINC02518, and their expression levels were significantly altered after BLNK silencing. These results suggest the important role of BLNK in CP/CPPS. BLNK may affect the proliferation and inflammatory factor secretion of CP/CPPS through calcium signaling pathway, which may be closely related to LINC02518.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148923","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":"Evaluation of Cardiac IL-11 and IL-11Rα Expression During T. cruzi Infection.","authors":"Yarlla Loyane Lira Braga, José Rodrigues do Carmo Neto, Pablo Igor Ribeiro Franco, Jordana Fernandes de Oliveira, Rafael Obata Trevisan, Fernanda Bernadelli de Vito, Flávia Aparecida de Oliveira, Mara Rúbia Nunes Celes, Marcos Vinícius da Silva, Juliana Reis Machado","doi":"10.1007/s10753-025-02322-4","DOIUrl":"https://doi.org/10.1007/s10753-025-02322-4","url":null,"abstract":"<p><p>Chagas disease (CD), caused by Trypanosoma cruzi, leads to cardiomyopathy in approximately 20-30% of infected individuals. Interleukin-11 (IL-11) has been implicated in cardiac fibrosis, although its immunological role in this context remains unclear. This study investigated the temporal dynamics of IL-11 and its receptor, IL-11Rα, expression in the hearts of C57BL/6 mice infected with 1,000 trypomastigote forms of the Y or Colombian strains of T. cruzi. Mice were euthanized at 5, 15, 30, 60, and 120 days post-infection (dpi). Survival, parasitemia, and body and heart weights were monitored. Cardiac tissue was analyzed for parasite nests, myocarditis, collagen deposition, and expression of the IL-11 receptor alpha (IL-11Rα). Cytokine profiles were evaluated by ELISA and Cytometric Bead Array. Histopathological analysis revealed more intense myocarditis, parasite load, and collagen deposition in mice infected with the Colombian strain. Both strains induced IFN-γ, TNF-α, and IL-6 in cardiac tissue; however, IL-10, IL-4, and IL-17 were detected only in the Y strain, indicating a more balanced immune response. Despite the absence of significant IL-11 upregulation in either infection, IL-11Rα expression was progressively increased over time and positively correlated with collagen deposition. These findings suggest that IL-11Rα may play a role in cardiac remodeling and fibrosis independently of IL-11 upregulation. The results reinforce the importance of T. cruzi strain variability in disease outcome and highlight the IL-11/IL-11Rα axis as a potential target for further investigation in Chagas cardiomyopathy.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039785","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":"Identification and Experimental Validation of OS-Related Gene Sets Based on Integrated Analysis of Single-Cell and Bulk RNA Sequencing Data with Machine Learning in Patients with Sepsis.","authors":"Linfeng Tao, Wei Tian, Ping Li, Yan Chen, Jun Liu","doi":"10.1007/s10753-025-02346-w","DOIUrl":"https://doi.org/10.1007/s10753-025-02346-w","url":null,"abstract":"<p><p>Sepsis is a severe organ dysfunction syndrome caused by a dysregulated host response to infection, closely associated with poor prognosis. It disrupts the balance between oxidative and antioxidative systems, which may ultimately result in cellular dysfunction and death. However, the key regulatory genes involved in this process remain unclear and require further investigation. In this study, we analyzed a single-cell RNA sequencing dataset from the Single Cell Portal and an oxidative stress (OS) gene set from GeneCards. We employed multiple algorithms and correlation analysis to identify OS-related gene sets that were upregulated in sepsis. Subsequently, RNA expression datasets from the Gene Expression Omnibus were used to filter for overlapping genes that were upregulated in the sepsis group. Furthermore, we used three machine learning algorithms to identify the optimal characteristic genes and verified them with animal models. Analysis of both scRNA-seq and bulk RNA-seq datasets using various algorithms revealed a significant increase in OS activity scores following sepsis, with heterogeneity observed across different cell layers. TXN, NUDT1, MAPK14, and CYP1B1 were found to be closely associated with the elevated OS levels in sepsis. Furthermore, our animal experiments confirmed a significant increase in OS activity in septic mice, along with elevated expression of TXN, MAPK14, and CYP1B1. This study is the first to elucidate the heterogeneity of oxidative stress at the single-cell level in sepsis. The identification of TXN, MAPK14, and CYP1B1 as pivotal regulators of oxidative stress in sepsis highlights their potential as biomarkers and therapeutic targets.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952671","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":"Angiotensin-(1-7) Mitigates Progression from Acute Kidney Injury to Chronic Kidney Disease Via Renin-Angiotensin System Modulation in a Murine Model.","authors":"Minzi Qiu, Yanxia Chen, Siyue Huang, Ben Ke, Xiangdong Fang, Chengyun Xu, Jinghai Hua","doi":"10.1007/s10753-025-02341-1","DOIUrl":"https://doi.org/10.1007/s10753-025-02341-1","url":null,"abstract":"<p><strong>Background: </strong> Acute kidney injury (AKI) often progresses to chronic kidney disease (CKD), presenting a significant clinical challenge. The renin-angiotensin system (RAS), particularly the protective arm involving Angiotensin-(1-7) (Ang-(1-7)), offers a potential therapeutic target to mitigate this progression. This study explores the effects of Ang-(1-7) in a murine model of ischemia-reperfusion (I/R) injury-induced AKI. Methods. Adult male Balb/c mice were subjected to bilateral renal I/R injury to induce AKI. Mice were then treated with various doses of Ang-(1-7). Key methods included enzyme-linked immunosorbent assay (ELISA) for serum biomarkers, immunohistochemistry for tissue-specific protein expression, and Western blotting for signaling pathway analysis. Key endpoints included serum levels of Angiotensin II (Ang II), Transforming Growth Factor-β1 (TGF-β1), Collagen I, and Superoxide Dismutase (SOD). Results. Ang-(1-7) treatment significantly reduced serum Ang II and TGF-β1 levels and decreased renal Collagen I expression. Notably, a dose-dependent increase in SOD was observed, indicating enhanced antioxidant defense. Additionally, Ang-(1-7) administration led to a marked reduction in renal fibrosis markers and inflammatory cytokines, including TGF-β1 and Collagen I, particularly in the high-dose group. The treatment also modulated the expression of key proteins involved in the RAS pathway, such as increased Angiotensin-Converting Enzyme 2 (ACE2) and decreased Angiotensin II Receptor Type 1 (AT1R) expression. Conclusion. This study highlights the novel therapeutic potential of Ang-(1-7) in preventing AKI progression to CKD by modulating the RAS towards a protective state. The findings provide a strong rationale for further clinical investigation of Ang-(1-7) or Mas receptor agonists as viable therapeutic strategies in kidney disease management.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952589","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":"Chemerin Exacerbates Pulmonary Inflammation in Type 2 Diabetes and Mycobacterium Tuberculosis Infection Comorbidity.","authors":"Giseli Furlan Corrêa, Núbia Sabrina Martins, Ualter Guilherme Cipriano, Ana Flávia Gembre, Daniel Rodrigues, Vinícius Bottura Apolloni, Leandra Naira Zambelli Ramalho, Thais Fernanda de Campos Fraga-Silva, Rita Tostes, Vânia Luiza Deperon Bonato","doi":"10.1007/s10753-025-02343-z","DOIUrl":"https://doi.org/10.1007/s10753-025-02343-z","url":null,"abstract":"<p><p>The adipokine chemerin is increased in the serum of individuals with obesity and type 2 diabetes. Patients with type 2 diabetes exhibit a threefold increased risk of developing tuberculosis, are more refractory to tuberculosis treatment and display more severe forms of the disease. Patients with type 2 diabetes and tuberculosis exhibit a dysfunctional immunological response characterized by a higher frequency of peripheral Th1 and Th17 cells, increased concentrations of pro- and anti-inflammatory cytokines, and a reduced microbicidal capacity compared to subjects affected exclusively by tuberculosis. In the present study, we investigated whether chemerin exerts a pro- or anti-inflammatory effect on macrophages in vitro and its role in the lungs of normoglycemic or hyperglycemic (obese plus type 2 diabetes) mice infected with Mycobacterium tuberculosis. Bone marrow-derived macrophages (BMDM) cultured with hyperglycemic medium and infected with M. tuberculosis secreted increased IL-6 and reduced IL-10 concentrations following chemerin treatment. BMDM from obese (fed with high-fat diet, HFD), non-diabetic mice were also pro-inflammatory, while BMDM from obese and diabetic mice (db/db) showed no significant difference compared to BMDM from normoglycemic mice (db/+). In vivo, db/db mice exhibited an increase of bacterial load and an exacerbated pulmonary immunopathology. Treatment of infected db/db mice with CCX832 chemerin receptor (ChemR23) antagonist significantly reduced pulmonary inflammation with no effect on bacterial load. Our findings show that blocking chemerin receptors may represent an adjuvant therapeutic strategy to mitigate pulmonary immunological response-mediated pathology accentuated by type 2 diabetes in active tuberculosis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952667","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":"Neutrophil Heterogeneity in Airway Inflammatory Diseases.","authors":"Dong-Yu Guo, Zheng-Yuan Liu, Xu-Chen Xu, Jin-Kang Yu, Jie-Sen Zhou, Zhou-Yang Li, Bai-Hui Lv, Ting Xu, Zhi-Hua Chen","doi":"10.1007/s10753-025-02351-z","DOIUrl":"10.1007/s10753-025-02351-z","url":null,"abstract":"<p><p>Neutrophils, the most abundant circulating leukocytes in humans, play key roles in infection and inflammation. The lungs represent a vital pool for neutrophils, serving as both a primary site of immune surveillance and a key battleground in inflammatory responses. However, neutrophil activation could be harmful; excessive or prolonged neutrophil activity can lead to unintended tissue damage and contribute to disease progression. Increasing evidence has highlighted the multifaceted roles of neutrophils in the pathogenesis and progression of airway inflammatory diseases. This review aims to elaborate the current understanding of neutrophil heterogeneity, functions, and mechanisms in various airway inflammatory diseases, including acute respiratory distress syndrome (ARDS), asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. Understanding the precise contributions of neutrophils in those airway inflammatory diseases would provide valuable insights into the complex immune landscape of the lungs and might open new avenues for targeted therapeutics.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872928","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":"Inactivated Bacillus subtilis R0179 Inhibits Porphyromonas Gingivalis-Induced Gingival Inflammation Via TLR2/NF-κB Signaling in a Murine Model of Periodontitis.","authors":"Weiwei Zhao, Lingli Ji, Jie Li, Dandan Liu, Chenying Zhang, Xiaozhe Wang, Yang Liu, Shuguo Zheng","doi":"10.1007/s10753-025-02348-8","DOIUrl":"https://doi.org/10.1007/s10753-025-02348-8","url":null,"abstract":"<p><p>This study aims to explore the mechanism by which heat-inactivated Bacillus subtilis (B. subtilis) R0179 modulates the TLR2/NF-κB signaling pathway to inhibit Porphyromonas gingivalis (P. gingivalis) induced gingival inflammation. In vitro experiments showed that P. gingivalis could invade gingival epithelial cells within 2 h of infection, as observed by transmission electron microscopy, and infection with P. gingivalis upregulated the expression of TLR1, TLR2, TLR4, TLR6, and p-NF-κB in gingival epithelial cells while promoting the release of IL-1β, IL-6, and TNF-α. The addition of heat-inactivated B. subtilis R0179 during P. gingivalis infection inhibited the expression of TLR2, TLR4, and p-NF-κB and suppressed the release of IL-1β, IL-6, and TNF-α. In vivo experiments using a mouse model of P. gingivalis-induced experimental periodontitis confirmed these findings, with heat-inactivated B. subtilis R0179 application reducing gingival inflammation, as observed by Hematoxylin and Eosin staining, and downregulating TLR2, TLR4, p-NF-κB, IL-1β, IL-6, and TNF-α signals, as detected by immunohistochemistry. Further investigation using TLR2 and TLR4 agonists revealed that TLR2 receptor agonists antagonized the B. subtilis R0179-induced downregulation of p-NF-κB, IL-6, IL-1β, and TNF-α. These results suggest that B. subtilis R0179 may inhibit P. gingivalis-induced gingival inflammation by suppressing the TLR2/NF-κB signaling pathway, consequently decreasing the production of pro-inflammatory cytokines.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798974","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":"Membrane-Associated RING-CH-Type Finger 6 Protects against Hypertension-Induced Cardiac Remodeling by Suppressing Cardiomyocyte Ferroptosis Through the Degradation of ACSL4.","authors":"Rui Hao, Xin Wang, Changhu Liu, Jianghua Xue","doi":"10.1007/s10753-025-02340-2","DOIUrl":"https://doi.org/10.1007/s10753-025-02340-2","url":null,"abstract":"<p><p>Hypertension serves as a major contributing factor to various cardiovascular disorders, including heart failure. Ferroptosis-induced cardiomyocyte loss is recognized as a novel contributor to myocardial remodeling in heart failure. Membrane-associated RING-CH-type finger 6 (Marchf6) is a newly identified gene that regulates ferroptosis and is implicated in various disease processes. However, the role of Marchf6 in modulating cardiomyocyte ferroptosis and its impact on hypertension-induced myocardial remodeling remain unexplored. This study aimed to investigate whether Marchf6 influences myocardial remodeling through the regulation of ferroptosis and to explore the underlying molecular mechanisms. Our findings indicated that there was a decrease in Marchf6 levels in both animal and cellular models established through Angiotensin II (Ang II) stimulation. Overexpression of Marchf6 conferred resistance to Erastin-induced ferroptosis, while Marchf6 knockdown increased sensitivity to ferroptosis. In the Ang II cellular model, Marchf6 overexpression enhanced cell viability, inhibited cardiomyocyte hypertrophy, and reversed ferroptosis-related indicators, whereas Marchf6 knockdown exhibited opposite effects. Animal model studies indicated that Marchf6 overexpression significantly improved cardiac function, alleviated myocardial hypertrophy and fibrosis, and suppressed ferroptotic death levels. Mechanistic investigations revealed that Marchf6 significantly regulated the stability of ACSL4 protein, with Marchf6 overexpression accelerating ACSL4 protein degradation. In cardiomyocytes overexpressing Marchf6, ACSL4 overexpression notably reversed the regulatory impact of Marchf6 on cardiac cell hypertrophy and ferroptosis triggered by Ang II. Collectively, our findings suggest that Marchf6 may mitigate cardiomyocyte ferroptosis by promoting ACSL4 degradation, thereby alleviating hypertension-induced myocardial remodeling. This study not only uncovers a novel regulatory mechanism of cardiomyocyte ferroptosis in myocardial remodeling but also presents a viable target for the management of hypertension-related cardiac diseases.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794336","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":"Inflammatory Association between Periodontal Disease and Systemic Health.","authors":"Fajer Hasan, Ankit Tandon, Hawra AlQallaf, Vanchit John, Mithun Sinha, Monica Prasad Gibson","doi":"10.1007/s10753-025-02317-1","DOIUrl":"https://doi.org/10.1007/s10753-025-02317-1","url":null,"abstract":"<p><p>Periodontitis is an oral disease that affects almost half of the adult population in United States. The complex relationship between oral and systemic health has been the focus of extensive research, aiming to unravel the mechanisms linking periodontal disease with various systemic conditions. This systematic review provides an overview of recent findings on the interrelationship between periodontitis and various systemic diseases. Specifically, it explores the associations between periodontal disease and several systemic disorders, including cardiovascular diseases, respiratory conditions, endocrine abnormalities, musculoskeletal disorders, and reproductive system issues. The review comprehensively examines the latest evidence on the bidirectional interactions between these diseases. By integrating data from several studies, this review provides insights into the underlying mechanisms including inflammatory pathways and microbial interactions, connecting the oral and systemic health. Understanding these relationships is essential for all healthcare providers, including periodontists and medical physicians alike, as it aids in the development of comprehensive treatment approaches that consider both periodontal and systemic health interactions and effects. For healthcare providers this understanding of complex interactions and connections is crucial for identifying disease etiology, treatment planning and determining prognosis for their patients. This includes multidisciplinary approach that address both periodontal and systemic health. In conclusion, this systematic review enhances the existing body of knowledge by providing a comprehensive and up-to-date synthesis of the most recent data available on the periodontal-systemic health relationship. By highlighting current findings, this review not only underscores critical areas for future research but also identifies opportunities for meaningful clinical application.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788861","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":"WFS1 Gene Mutation (c.2389G > A) Induces Immune Disorders by Promoting DC Maturation through Inhibition of TMEM176A.","authors":"Wei Lin, Yuanhui Qiu, Chenyinuo Tan, Ziyu Liu, Yi Yang, Yijie He, Jiarui Zhao, Jing Cheng, Zhaopeng Wang, Minghao Li, Lijie Wang, Mengqi Wang, Min Zhang","doi":"10.1007/s10753-025-02325-1","DOIUrl":"https://doi.org/10.1007/s10753-025-02325-1","url":null,"abstract":"<p><p>Mutations in the WFS1 gene, encoding wolframin (WFS1), are known to cause endoplasmic reticulum (ER) stress and lead to Wolfram Syndrome (WS). However, the role of WFS1 in immune inflammation remains unexplored. In this study, we identified that the WFS1 gene mutation (c.2389G > A) not only results in WS associated symptoms but also induces the elevated levels of pro-inflammatory cytokines (i.e. TNF-α, IL-1β, and IL-6), and promotes the maturation of dendritic cell (DC) in WFS1 mutated mice. Silencing the WFS1 gene in DCs also promoted DC maturation and inflammation while also increasing DC apoptosis. Further investigation revealed that WFS1 regulates the expression of X-box binding protein 1 (XBP1), which negatively modulates the expression of TMEM176A, thereby affecting the maturation, inflammatory response, and function of DCs. Additionally, WFS1 influences DC apoptosis under ER stress (ERS) through the ATF4/CHOP pathway. Notably, the WFS1 mutation (c.2389G > A) induces immune cell apoptosis in experimental autoimmune uveitis (EAU). This study is the first to report the immune regulatory mechanism of WFS1 in DCs. The identification of a systemic chronic inflammatory state associated with WFS1 deficiency offers new insights that may facilitate the development of innovative, personalized therapeutic approaches for WS.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788862","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}