Immunologic Research最新文献

{"title":"Identifying potential signatures of immune cells in hepatocellular carcinoma using integrative bioinformatics approaches and machine-learning strategies.","authors":"Xingchen Liu, Bo Pan, Jie Ding, Xiaofeng Zhai, Jing Hong, Jianming Zheng","doi":"10.1007/s12026-024-09585-3","DOIUrl":"10.1007/s12026-024-09585-3","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a malignant tumor regulated by the immune system. Immunotherapy using checkpoint inhibitors has shown encouraging outcomes in a subset of HCC patients. The main challenges in checkpoint immunotherapy for HCC are to expand treatment options and to broaden the beneficiary population. Therefore, the search for potential signatures of immune cells is meaningful in the development of immunotherapy for HCC. The HCC related datasets were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Differential expression analysis and functional analysis were performed first. Then support vector machine-recursive feature elimination (SVM-RFE), random forests (RF), least absolute shrinkage and selection operation (LASSO), and weighed gene co-expression network analysis (WGCNA) were employed to screen for critical genes, and receiver operating characteristic (ROC) analysis was performed to compare diagnostic performance. Subsequently, single-sample gene set enrichment analysis (ssGSEA) was used to explore the relationship between signatures and immune cells. Finally, we validated the expression of these biomarkers in human HCC samples. 531 overlapping differentially expressed genes (DEGs) were identified. Furthermore, enrichment analysis revealed pathways associated with immune activation processes, immune cell involvement and inflammatory signaling. After using multiple machine-learning strategies, extracellular matrix protein 1 (ECM1), leukemia inhibitory factor receptor (LIFR), sushi repeat containing protein X-linked (SRPX), and thromboxane A2 receptor (TBXA2R) were identified as critical signatures, and exhibited high expression in tumor-adjacent normal tissues. According to the ssGSEA results, ECM1, LIFR, SRPX and TBXA2R were all significantly associated with diverse immune cells, such as monocytes and neutrophils. Moreover, immunostaining of human HCC samples showed that these critical signatures all colocalized with CD14-positive monocytes. Our findings report the potential signatures of immune cells in HCC and confirm that they localize in monocytes of tumor-adjacent normal tissues. ECM1, LIFR, SRPX and TBXA2R could become new potential targets for predictive diagnosis, early intervention and immunotherapy of HCC in the future.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"46"},"PeriodicalIF":3.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative bioinformatics and experimental analyses identify U2SURP as a novel lactylation-related prognostic signature in esophageal carcinoma.","authors":"Xuan Zheng, Xiaoru Zhang, Dan Li, Zhuo Wang, Jun Zhang, Jingwu Li, Yufeng Li","doi":"10.1007/s12026-024-09589-z","DOIUrl":"10.1007/s12026-024-09589-z","url":null,"abstract":"<p><p>The lactylation modification has been implicated in several cancer types; however, the role of lactylation modification-related genes in esophageal carcinoma (EC) remains underexplored. Utilizing a set of 16 lactylation modification-related genes, cohorts of patients with EC were stratified into two distinct clusters, characterized by significant disparities in both survival outcomes and the immune microenvironment. An extensive bioinformatics analysis unveiled 382 differentially expressed genes (DEGs) between these two clusters. A subsequent univariate Cox regression analysis identified 24 DEGs specifically associated with lactylation, forming the basis of a constructed lactylation-related score. The resultant lactylation-related score exhibited notable predictive efficacy for survival and other clinicopathological traits, which was validated through calibration curves, Kaplan-Meier survival curves and the Wilcoxon test. Moreover, the lactylation-related score displayed a close correlation with immune cell infiltration in EC. Notable differential expressions of immune checkpoints and regulators were observed between groups stratified by low and high lactylation scores, with the latter exhibiting a more favorable response to anti-PD-1/PD-L1 therapy. Furthermore, the expression profile of U2 snRNP associated SURP domain containing (U2SURP), a constituent of the lactylation-related score, underwent both ex vivo and in vitro validation. The expression of U2SURP was significantly associated with lactylation levels, histological grade and tumor stage. Notably, knockdown of U2SURP expression inhibited the lactylation levels, immune genes IL-1A and IL-1B, proliferation, migration and invasion of EC cells. In conclusion, the lactylation-related score developed in the present study showed promise in predicting the prognosis and immunotherapeutic responses among patients with EC. Moreover, the identification of U2SUPR as a novel oncogene in EC suggests its potential as a prospective therapeutic target for EC treatment.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"45"},"PeriodicalIF":3.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ability of CD4^dimCD8⁺ T cells to distinguish between Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis and pediatric infectious mononucleosis.","authors":"Can Liu, Aijun Zou, Xianyu Wang, Caizhi Huang","doi":"10.1007/s12026-025-09597-7","DOIUrl":"10.1007/s12026-025-09597-7","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (IM) are characterized by fever, hepatomegaly, and splenomegaly, but HLH has a 50% lethality rate. Therefore, this study aimed to compare the laboratory findings in differentiating EBV-HLH children from IM children who have fever, hepatomegaly, or splenomegaly. A total of 131 IM patients and 29 EBV-HLH pediatric patients with fever, hepatomegaly, or splenomegaly were enrolled in our study. The clinical traits and laboratory findings were analyzed, and a predictive regression analysis was also performed. EBV-HLH patients had a lower set of diagnostic markers, which included fibrinogen (FIB), white blood cells (WBC), hemoglobin (Hb), and platelet (PLT), compared to IM patients. Triglyceride (TG) and ferritin were elevated obviously in EBV-HLH patients compared to IM patients. CD4^dimCD8⁺ T cells are highly activated T cells. EBV-HLH patients experienced a significant decrease in the absolute number and ratio of CD4^dimCD8⁺T cells (CD4^dimCD8⁺T#, CD4^dimCD8⁺T%) compared to IM patients in our study. The AUC of CD4^dimCD8⁺ T # in the diagnosis of EBV-HLH was 0.920 with a sensitivity of 86.2% and a specificity of 90.1%. A logistic regression analysis was developed to improve sensitivity. The results revealed that lower levels of Hb, FIB, and CD4^dimCD8⁺T cells were risk factors for EBV-HLH. The regression model for separating EBV-HLH from EBV-IM had an AUC of was 0.996 with a sensitivity of 100% and a specificity of 95.3%. The ratio and absolute number of CD4^dimCD8⁺T cells were decreased in IM and EBV-HLH patients. EBV-HLH can be identified in IM patients with fever, hepatomegaly, or splenomegaly by detecting Hb, FIB, and the absolute number of CD4^dimCD8⁺T cells.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"43"},"PeriodicalIF":3.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amphibian cellular immune response to chytridiomycosis at metamorphic climax.","authors":"Josephine E Humphries, Allan Hicks, Chantal Lanctôt, Hamish McCallum, David Newell, Laura F Grogan","doi":"10.1007/s12026-025-09599-5","DOIUrl":"10.1007/s12026-025-09599-5","url":null,"abstract":"<p><p>The fungal disease chytridiomycosis (caused by Batrachochytrium dendrobatidis [Bd]) is a primary contributor to amphibian declines. The frog metamorphic stages, characterised by extensive physiological reorganisation and energy expenditure, have heightened susceptibility to Bd. However, little is known about how these metamorphic stages respond immunologically to Bd infection. In this study, we examined Bd infection and the cellular immune response of Mixophyes fleayi at Gosner stages 40, 42 and 45, using blood smears and skin and liver histology. Although proportional differences were observed, the impact of Bd exposure appeared negligible prior to Gosner stage 45 (onset of morbidity), with no significant differences observed in absolute leukocyte counts for blood or liver samples between control and Bd-exposed groups at Gosner stages 40 and 42. Animals exhibiting clinical signs at Gosner stage 45 demonstrated significant elevation in liver leukocyte counts, blood neutrophil and monocyte counts and neutrophil-to-lymphocyte ratios. These findings are reminiscent of the amplified inflammatory response characteristic of immunopathology in clinically infected amphibians. Interestingly, a subset of exposed animals that had apparently cleared infections at Gosner stage 45 had similar blood leukocyte counts but reduced liver leukocyte counts compared to naïve controls. This could be a consequence of prior cellular consumption during pathogen removal or effective immune regulation via anti-inflammatory protective feedback mechanisms. We recommend targeted gene expression analyses (e.g. immunomodulatory cytokines) to establish the mechanisms responsible for the varied immune expression and infection outcomes across metamorphosis.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"44"},"PeriodicalIF":3.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α₂-adrenoblockers modulatory effect on the noise-mediated several biochemical and morpho-immuno-histochemical changes in the rat's blood plasma and tissues.","authors":"Ashkhen L Manukyan, Anna S Khachatryan, Seda H Harutyunyan, Ruzan M Simonyan, Narine V Tumasyan, Lilit M Sukiasyan, Inesa K Sahakyan, Madlena A Babayan, Lilit S Hunanyan, Hovsep N Babayan, Konstantin B Yenkoyan, Magdalina M Melkonyan","doi":"10.1007/s12026-025-09594-w","DOIUrl":"10.1007/s12026-025-09594-w","url":null,"abstract":"<p><p>Experimental studies of chronic noise exposure in modern urban life testified about oxidative stress due to the corresponding hormones effects leading to accumulation of reactive oxygen species and endothelial dysfunction. This study aims to evaluate the protective effect of α2-adrenoblockers to modulate oxidative stress and corticosterone levels due to chronic noise exposure. To achieve this, we examined the effects of beditin (2-aminothiozolyl-1,4-benzodioxane) and mesedin (2-(2-methyl-amino-thiozolyl)-1,4-benzodioxane hydrochloride), along with changes in corticosterone, Ca2 + content, and morphological alterations in various tissues under noise-induced stress. Beyond this, detection of immune-reactivity and proliferation of Galarmin-containing cells in adrenals, and isolation of the total fractions of superoxide-producing associate from the rat liver under noise exposure and the beditin and mesedin actions on them were pertinent. Experiments were provided on the albino female rats divided into four groups: (1) control, (2) noise-exposed, (3) noise-exposed and beditin-injected (2 mg/kg, i.p.), and (4) noise-exposed and mesedin-injected (10 mg/kg, i.p.) animals. The noise exposure was of 91 dBA noise on 60 days with a daily duration of 8 h. For the first time, the total fractions of superoxide-containing associates were separated from the cell membranes of the rat liver tissue under the chronic noise stress conditions and the regulative effects of the α₂-adrenoblockers. Increased ⁴⁵Ca²⁺ and decreased corticosterone levels in the mentioned tissues, as well as dystrophic changes, were observed under the chronic noise exposure. Prominently, α₂-adrenoblockers showed antioxidant effects, modulating pathological shifts of the noise-induced stress.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"42"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current utilization trend of immortalized mast cell lines in allergy research: a systematic review.","authors":"Ashley Jia Wen Yip, Yu Zhao Lee, Audrey Siew Foong Kow, Carisa Su-Ann Wong, Ming-Tatt Lee, Chau Ling Tham, Ji Wei Tan","doi":"10.1007/s12026-024-09562-w","DOIUrl":"10.1007/s12026-024-09562-w","url":null,"abstract":"<p><p>Today, in the modern world, allergic diseases, also described as atopic allergies, are classified as a type of multifactorial disorder due to the complex interplay between genetics, environment, and socioeconomic factors that influence the disease's manifestation, severity, and one's predisposition to allergic diseases. It is undeniable that many reported studies have pointed out that the mast cell is one of the leading key players involved in triggering an allergic reaction. To improve our understanding of the molecular and cellular mechanisms underlying allergy, various mast cell lines have been employed in vitro to study the pathogenesis of allergic diseases for the past decades. However, there is no consensus on many fundamental aspects associated with their use, such as the effects of culture media composition and the type of inducer used for cell degranulation. As the standardization of research protocols and disease models is crucial, we present the outcome of a systematic review of scientific articles using three major immortalized in vitro mast cell lines (HMC-1, LAD2, and RBL-2H3) to study allergy. This systematic review described the cell source, culture conditions, inducers used for degranulation, and mediators released for examination. We hope that the present systematic review may help to standardize the use of immortalized in vitro mast cell lines in allergy research and serve as a user's guide to understand the fundamental aspects of allergy as well to develop an effective allergy therapy in the future for the betterment of human good health and wellbeing.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"41"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A central role of stimulator of interferon genes' adaptor protein in defensive immune response.","authors":"Anju Kaushal","doi":"10.1007/s12026-024-09587-1","DOIUrl":"10.1007/s12026-024-09587-1","url":null,"abstract":"<p><p>Cytotoxic DNAs, methylation, histones and histones binding proteins are speculated to induce DNA sensors. Under stressed condition, the antigenic patterns, PAMPs and DAMPs, trigger the hyperactive innate response through DNA, DNA-RNA hybrids, oligonucleotides, histones and mtDNA to initiate cGAMP-STING-IFN I cascade. HSV -1&2, HIV, Varicella- Zoster virus, Polyomavirus, Cytomegalovirus, and KSHV negatively regulate the STING-MAVS-TBK-1/1KKE pathway. Implications in STING-PKR-ER regulation often run into causing senescence and organ fibrosis. Post-translational modifications such as, phosphorylation, ubiquitination, SUMOylation, hydrolysis etc. downstream the processing of cGAS-STING that determine the fate of disease prognosis. Self-DNA under normal circumstances is removed through DNase III action; however, its deficiency is the great cause of RA diseases. Regular STING activation in chronic diseases could lead to exacerbate the neurodegenerative disorders due to constant mtDNA leakage. 2' 3' cGAMP or CDN or its associates are being explored as STING agonist therapeutics to treat solid/metastatic tumors to help infiltrate the immune cells, cytokines and chemokines to regulate the protective response. Liposomes, polymer nanoparticles, and cell-derived nanoparticles are also meant to increase the drug efficiency and stability for desired immune response to enhance the IFN I production. This review highlights the implications of cGAMP-STING- IFN I cascade and related pathways involved in the disease prognosis, therapeutics and considering the gaps on different aspects to utilize its greater potential in disease control.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"39"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tertiary lymphoid structure signatures are associated with survival and immunotherapy response in lung adenocarcinoma.","authors":"Bing Han, Jikun Deng, Rongmei Fan","doi":"10.1007/s12026-025-09595-9","DOIUrl":"10.1007/s12026-025-09595-9","url":null,"abstract":"<p><p>The presence of tertiary lymphoid structures (TLSs) has been correlated with improved prognosis and clinical outcomes in response to immunotherapy in certain solid tumors. However, the precise role of TLSs in lung adenocarcinoma (LUAD) remains unclear. Four datasets of LUAD were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The TLSs model was constructed using a multivariate Cox proportional hazards model. GO and KEGG analyses were performed to explore the biological process associated with the TLSs model. The ESTIMATE and CIBERSORT algorithms were employed to quantify immune infiltration status. TLSs signature genes (TSGs) were identified, including chemokine signature genes, TFH cell markers, TH1 cell and B cell markers, and a plasma cell marker. Diagnostic evaluations identified key genes with high diagnostic value, particularly among chemokine signature genes and TFH cells markers. Furthermore, high expression of CCL20 and IL1R2 was correlated with poorer outcomes, while other TSGs indicated more favorable prognoses. A novel TLSs score model was constructed, integrating 4 TSGs (SGPP2, MS4A1, IL1R2 and CCL20), which accurately predicted patient survival and was independently associated with prognosis. Additionally, the TLSs score served as a robust indicator for LUAD survival prediction, outperforming traditional staging systems. Comprehensive analyses of enriched pathways and immune cell infiltration patterns revealed that this score involved in metabolic processes and immune cell regulation. Furthermore, the TLSs score showed potential as an indicator of response to immunotherapy, with higher scores associated with reduced expression of immune checkpoint genes and poorer response rates. The TLSs score may serve as a predictor of prognosis and immunotherapeutic response in LUAD. These findings may offer new insights on the study of malignancy and personalized immunotherapy for LUAD patients.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"40"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual neutralization of TGF-β and IL-21 regulates Th17/Treg balance by suppressing inflammatory signalling in the splenic lymphocytes of Staphylococcus aureus infection-induced septic arthritic mice.","authors":"Rochana Pramanik, Sreya Chattopadhyay, Biswadev Bishayi","doi":"10.1007/s12026-024-09586-2","DOIUrl":"10.1007/s12026-024-09586-2","url":null,"abstract":"<p><p>Septic arthritis (SA) caused by Staphylococcus aureus is a severe inflammatory joint disease, characterized by synovitis accompanied with cartilage destruction and bone erosion. The available antibiotic treatment alone is insufficient to resolve the inflammation that leads to high rates of morbidity and mortality. Among the CD4⁺ T helper lymphocytes, the Th17 and Tregs are key regulators of immune homeostasis. A high Th17 could lead to autoimmunity, whereas an increase in Tregs indicates immunosuppression. Depending on the external cytokine milieu, naïve CD4⁺ T cells transform into either Th17 or Treg cell lineage. TGF-β in the presence of IL-21 produces Th17 cells and drives the inflammatory cascade of reactions. We studied the effects of in vivo neutralization of TGF-β and IL-21 in septic arthritic mice to control arthritic inflammation, which has not been studied before. The arthritic index showed maximum severity in the SA group which substantially reduced in the Ab-treated groups. Flow cytometric analyses of peripheral blood collected from mice at 9DPI revealed the highest Th17/Treg ratio in the SA group but least in the combined-antibody-treated group. TGF-β1 and IL-21 cytokine production from serum, spleen, and synovial tissue homogenates was significantly reduced in the dual Ab-treated group than in the untreated SA group. From the Western blot analyses obtained from splenic lymphocytes at 9 DPI, we elucidated the possible underlying mechanism of interplay in downstream signalling involving the interaction between different STAT proteins and SOCS, NF-κB, RANKL, mTOR, iNOS, and COX-2 in regulating inflammation and osteoclastogenesis. On endogenous blockade with TGF-β and IL-21, the Th17/Treg ratio and resultant arthritic inflammation in SA were found to be reduced. Therefore, maintaining the Th17/Treg balance is critical to eradicate infection as well as suppress excessive inflammation and neutralization of TGF-β and IL-21 could provide a novel therapeutic strategy to treat staphylococcal SA.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"38"},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irisin-mediated KEAP1 degradation alleviates oxidative stress and ameliorates pancreatitis.","authors":"Nan Tang, Wendi Li, Hezhen Shang, Zhen Yang, Zengyin Chen, Guangjun Shi","doi":"10.1007/s12026-024-09588-0","DOIUrl":"10.1007/s12026-024-09588-0","url":null,"abstract":"<p><p>Oxidative stress (OS) injury is pivotal in acute pancreatitis (AP) pathogenesis, contributing to inflammatory cascades. Irisin, a ubiquitous cytokine, exhibits antioxidant properties. However, the role of irisin in AP remains inconclusive. Our study aims to elucidate irisin expression in AP patients and investigate its mechanism of action to propose a novel treatment strategy for AP. Serum irisin levels in 65 AP patients were quantified using an enzyme-linked immunosorbent assay and correlated with disease severity scores. Core genes implicated in AP-related oxidative stress were identified and screened via bioinformatics analysis. The therapeutic efficacy of irisin in AP was confirmed using a murine cerulein-induced AP model. The intrinsic mechanism of irisin's antioxidative stress action was investigated and verified in pancreatic AR42J cells (Supplementary Fig. 1). Common targets shared by irisin and AP were further validated using a molecular docking model which was constructed for virtual docking analysis. This study investigated alterations in redox status in AP and found a significant reduction in serum irisin levels, correlating inversely with AP severity. In a murine AP model, we showed that irisin triggers an antioxidative stress program via the KEAP1 gene; this process helps reestablish redox balance by decreasing the buildup of reactive oxygen species (ROS) and suppressing the secretion of inflammatory mediators within pancreatic tissues Notably, increased KEAP1 expression counteracted the antioxidative effects of irisin. Our findings unveil a novel therapeutic mechanism for AP, wherein irisin inhibits KEAP1 to alleviate OS. Increasing irisin levels in vivo presents a promising strategy for AP treatment.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"37"},"PeriodicalIF":3.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}