Immunobiology最新文献

{"title":"Sexual dimorphism in neutrophil function: Unveiling the discriminative nature of male and female neutrophils","authors":"Richard F. Kraus ,&nbsp;Nina Doblinger ,&nbsp;Michael A. Gruber ,&nbsp;Maria S. Wagner ,&nbsp;Johanna Rosenberger","doi":"10.1016/j.imbio.2025.153128","DOIUrl":"10.1016/j.imbio.2025.153128","url":null,"abstract":"<div><h3>Background</h3><div>Women and men are different on many biological levels. Mounting evidence is now recognized that even the immune system has some significant sex differences, which are mainly cell mediated. This study investigated sex-specific differences in function and regulation of polymorphonuclear neutrophil granulocytes (PMNs) in male and female healthy human donors to gain a deeper understanding of the immune response and potential sex-specific dimorphism in immunology.</div></div><div><h3>Methods</h3><div>PMNs were obtained from whole blood samples of healthy female and male donors by leuko−/lymphospin density centrifugation. Chemotaxis assays using μ-slide chemotaxis chambers were performed, in which N-formylmethionin-leucyl-phenylalanine (fMLP) stimulated PMNs migrated through a type I collagen matrix. We measured the production of reactive oxygen species (ROS), the release of myeloperoxidase (MPO), and the formation of Neutrophil Extracellular Traps (NETs). Additionally, a flow cytometry assay was conducted to examine functional variations of neutrophil surface markers CD62L, CD11b, and CD66b, as well as the oxidative burst in PMNs obtained from male and female donors.</div></div><div><h3>Results</h3><div>Sex specific differences of neutrophil function could be determined. Male-derived PMNs initially migrated further distances, while female-derived PMNs showed more targeted movement. However, as the observation period progressed, male-derived PMNs began to exhibit more targeted migration, maintaining straightness towards the end. Differences in neutrophil surface marker expression were observed, with greater levels of CD11b and CD66b on male-derived PMNs after 2 h resting. The different immune effects between the sexes were seen in live cell imaging as well as in flow cytometry analyses.</div></div><div><h3>Conclusion</h3><div>The study revealed significant functional differences between PMNs from male and female donors. To gain reliable results in future PMN studies, it is crucial to consider the sex of the donor.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153128"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354693","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":"ATP–NLRP3 inflammasome axis enhances the immunosuppressive effect of myeloid-derived suppressor cells","authors":"Tatsuya Ando ,&nbsp;Kouhei Sakurai ,&nbsp;Masato Hoshi ,&nbsp;Hiroyuki Tezuka ,&nbsp;Yasuhiro Sakai ,&nbsp;Taku Kato ,&nbsp;Hiroyasu Ito","doi":"10.1016/j.imbio.2025.153119","DOIUrl":"10.1016/j.imbio.2025.153119","url":null,"abstract":"<div><div>The effectiveness of immune checkpoint inhibitors is diminished by the presence of myeloid-derived suppressor cells (MDSCs). Recent studies indicate that the NLR family pyrin domain-containing 3 (NLRP3) inflammasome regulates MDSC function, thereby reducing the efficacy of immune checkpoint inhibitors. However, the specific mechanism by which NLRP3 expression induces the immunosuppressive effects in MDSCs remains unclear. Here, we demonstrate that the adenosine triphosphate (ATP)–NLRP3 inflammasome axis enhances the immunosuppressive effects of MDSCs. We found that ATP increases the mRNA levels of immunosuppressive molecules in MDSCs, leading to the suppression of T cell proliferation. Additionally, we showed the efficacy of a novel immune checkpoint therapy that combines an ATP receptor inhibitor (P2X7 receptor inhibitor), an NLRP3 inhibitor, and an anti-PD-L1 antibody (Ab). This combination treatment significantly inhibited tumor growth compared to treatment with only the NLRP3 inhibitor and anti-PD-L1 Ab. These results suggest that the ATP–NLRP3 axis enhances the immunosuppressive effect of MDSCs. In conclusion, this study elucidates the mechanism through which MDSCs acquire immunosuppressive functions, potentially informing the development of novel cancer immunotherapies.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153119"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119337","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":"Anti-retroviral treatment of HIV infected individuals improves the ex vivo generation of memory-like NK cells","authors":"Kalavati Lalsare MSc,&nbsp;Shubhangi Bichare MSc,&nbsp;Sheetal Mulay MSc,&nbsp;Rajani D. Bagul MSW,&nbsp;Suvarna Sane M.Phil,&nbsp;Madhuri Thakar PhD","doi":"10.1016/j.imbio.2025.153127","DOIUrl":"10.1016/j.imbio.2025.153127","url":null,"abstract":"<div><div>The ability of Natural Killer (NK) cells, to generate memory-like responses against viruses including – HIV, opened up possibility of their application as immune therapy. We attempted to generate memory-like NK cells from HIV exposed and unexposed primary NK cells. The PBMCs of HIV uninfected and infected individuals (LTNPs, ART experienced and with progressive disease) were preactivated with cytokine cocktail (CC) of IL12, IL 15 and IL 18 with or without HIV-1 Env C or only IL 15 and restimulated with CC + HIV-1 Env C after seven days' rest. The CD56+ NK cells from the cultures were assessed for IFN-γ, TNF-α, and perforin secretion and expression of CD107a using multiparametric flow cytometry. Higher functionality was observed in case of pre-activation with CC with or without HIV-1 Env C as compared to only Il 15 across study groups. However, the functionality of the generated memory -like NK cells was significantly higher in case of LTNPs and the ART experienced individuals only. Low frequency of functional NK cells generated from HIV unexposed NK cells indicate probable specificity to HIV. The memory-like NK cells from ART experienced individuals generated after CC and CC+ HIV-1C preactivation showed good proliferating ability and also an ability to lyse the allogenic HIV infected CD4+ T cells. This work highlighted that HIV specific memory-like NK cells can be generated from the NK cells of HIV infected individuals with robust immune status after pre-activation with cytokine cocktail with or without HIV-1C. Although preliminary, these findings suggest that memory-like NK cells could have potential for use in immunotherapy aimed at clearing viral reservoirs.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153127"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408872","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":"Stability testing of HPCs and MNCs from apheresis products","authors":"Jinxia Ma,&nbsp;Lipei Shao,&nbsp;Tatyana Fuksenko,&nbsp;Hui Liu,&nbsp;Chunjie Jiang,&nbsp;Yihua Cai,&nbsp;Yong Soo Kim,&nbsp;Kathryn Martin,&nbsp;Larry Moses,&nbsp;Nan Zhang,&nbsp;Anh Dinh,&nbsp;Robert P. Somerville,&nbsp;David F. Stroncek,&nbsp;Ping Jin","doi":"10.1016/j.imbio.2025.153112","DOIUrl":"10.1016/j.imbio.2025.153112","url":null,"abstract":"<div><h3>Background</h3><div>Hematopoietic progenitor cells (HPCs) and mononuclear cells (MNCs) are critical components of cell-based therapies, including bone marrow transplantation and regenerative treatments. Evaluation of the characteristics of these products during collection, storage, and transport is essential for maintaining cell viability and functionality. In this study, we evaluated the functional and molecular stability of samples collected for the evaluation of fresh HPC and MNC products. The samples stored at 4 °C for up to 4 days and were evaluated using white blood cell (WBC) counts, flow cytometry, and bulk RNA sequencing (RNA-seq) across five time points.</div></div><div><h3>Methods</h3><div>HPC samples from seven products (June–December 2022) and MNC samples from six products (October 2022–August 2023) were analyzed on days 0 through 4 after collection. WBC counts were measured, and viability was assessed using 7-AAD staining and flow cytometry. HPC samples were stained with antibodies against CD34, CD3, CD19, CD56, CD14, CD16, CD15, and CD45, while MNC samples were stained with antibodies directed to CD3, CD4, CD8, CD19, CD56, CD14, CD16, CD15, and CD45. Total RNA was isolated from each sample and subjected to bulk RNA-seq to assess transcriptomic changes during storage.</div></div><div><h3>Results</h3><div>While WBC counts varied between products, no significant differences were observed across time points within individual products. Flow cytometry markers remained relatively stable over time in both HPC and MNC samples, although greater variability was observed in HPCs. A modest decrease in lymphocyte percentages was noted at later time points, primarily driven by a reduction in CD3+ cells; however, these changes were not statistically significant. Cell viability declined significantly over time within individual products and showed inter-product variability. RNA-seq analysis revealed stable gene expression profiles in MNC samples across all time points. In contrast, HPC samples exhibited notable transcriptomic changes as early as day 1 of storage at 4 °C, indicating greater molecular instability.</div></div><div><h3>Conclusion</h3><div>WBC counts and flow cytometry markers remain stable for up to 3 days in samples collected from fresh HPC and MNC products when stored at 4 °C, although cell viability progressively declines. However, RNA-seq data reveal early transcriptomic changes in HPC samples, suggesting that immediate evaluation of these samples is critical to preserve their molecular integrity and functionality. These findings support the feasibility of delayed phenotypic analysis but emphasize the need for prompt molecular assays in HPC-based applications.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153112"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005236","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 Role of WNT5A-mediated proteomic and phosphoproteomic regulatory networks in rheumatoid arthritis","authors":"Ping Jiang ,&nbsp;Daxi Ma ,&nbsp;Youji Jia ,&nbsp;Honghong Ma ,&nbsp;Yajuan Guo ,&nbsp;Juhua Zhang ,&nbsp;Wei Yan ,&nbsp;Xiaobing Xi","doi":"10.1016/j.imbio.2025.153137","DOIUrl":"10.1016/j.imbio.2025.153137","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to investigate the role of the <em>WNT5A</em> signaling pathway in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and uncover the impact of <em>WNT5A</em> on cellular function and signal transduction through proteomic and phosphoproteomic analyses.</div></div><div><h3>Methods</h3><div>MH7A cells were treated with recombinant <em>WNT5A</em> (rhWNT5A), and differential expression proteins (DEPs) and phosphoproteins (DEPPs) were identified through proteomic and phosphoproteomic analyses. Data were further analyzed via volcano plots, heatmaps, enrichment analysis, and protein-protein interaction (PPI) networks to identify key biological processes and signaling pathways regulated by <em>WNT5A.</em></div></div><div><h3>Results</h3><div>Significant changes in the expression of numerous DEPs and DEPPs were observed following rhWNT5A treatment, including proteins closely related to lipid metabolism, cell migration, inflammation, and cell proliferation. PPI network analysis revealed that key regulatory proteins, such as <em>HNRNPA1</em>, <em>RANBP2</em>, <em>BCLAF1</em>, <em>NPM1</em>, and <em>SMARCA4</em>, occupy central positions in the network. Enrichment analysis indicated that <em>WNT5A</em> influences essential signaling pathways, such as <em>AMPK</em>, <em>mTOR</em>, <em>VEGFA-VEGFR2</em>, Notch, and endoplasmic reticulum stress, regulating cellular energy metabolism, inflammatory response, and cytoskeletal remodeling. Kinase activity analysis identified significant changes in kinases such as <em>CDK1</em>, <em>CSNK2A1</em>, <em>EEF2K</em>, <em>AURKA</em>, and <em>AURKB</em>, which were further integrated into the kinase-substrate regulatory network.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that <em>WNT5A</em> significantly influences the biological functions and inflammatory responses of RA-FLS by regulating key biological processes and signaling pathways. The integrated proteomic and phosphoproteomic analyses provide insights into the potential mechanisms and regulatory networks of <em>WNT5A</em> in RA, suggesting its application as a potential therapeutic target.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153137"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516874","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":"Copper regulates the expression of immune genes in microglial cells in vitro","authors":"Laura Craciun,&nbsp;Sandra E. Muroy,&nbsp;Kaoru Saijo","doi":"10.1016/j.imbio.2025.153145","DOIUrl":"10.1016/j.imbio.2025.153145","url":null,"abstract":"<div><div>Copper, a transition metal, plays crucial roles in various physiological functions, including those of the nervous and immune systems. Dysregulation of copper homeostasis is linked to several diseases, such as neurodegenerative diseases. Since dysfunctional microglial immunity can also contribute to such diseases, we investigated the role of copper in microglial immunity. Currently, the roles of copper in microglial immunity are considered complex and multifaceted, with both anti- and pro-inflammatory effects having been proposed. In the current study, we found that both increased and decreased copper levels suppressed lipopolysaccharide (LPS)-mediated inflammation in microglial cells, as determined by RT-qPCR analysis. RNA sequencing (RNA-seq) analysis confirmed that increased copper levels reduced the inflammatory response to LPS; however, it also showed that decreased copper levels affected genes involved in cell proliferation, transcription, and autophagosome regulation. These findings suggest that copper is vital for maintaining normal immune functions in microglia, and that both copper excess and deficiency can disrupt microglial immunity.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153145"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681494","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 anti-tumor and immunomodulatory effect of α-tocopherol on tumor microenvironment in an in vitro model of colon cancer","authors":"Tahereh Azari ,&nbsp;Fatemeh Sadeghi ,&nbsp;Kosar Malekpour ,&nbsp;Farzad Nasri ,&nbsp;Elahe Safari","doi":"10.1016/j.imbio.2025.153138","DOIUrl":"10.1016/j.imbio.2025.153138","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) requires effective preventive measures due to its high prevalence, mortality rate, and impact on patients' lives. Therefore, this study aimed to assess the immunomodulatory effects of α-tocopherol (α-TOC) within the tumor microenvironment (TME) of CRC using a co-culture model.</div></div><div><h3>Methods</h3><div>To characterize the biological effects of vitamin E, apoptosis assays, scratch tests, and real-time PCR were performed to investigate the direct effect of α-TOC (2.2, 22, and 220 μM) on the viability, migration, and pathway mechanisms of the SW480 CRC cell line. PBMCs (peripheral blood mononuclear cells) were co-cultured with the SW480 to assess the effects within the TME and then treated with α-TOC. We evaluated the effect of α-TOC on the viability of PBMC and the co-culture of PBMC+SW480 using an MTT assay. Additionally, we performed ELISA and flow cytometry to assess the effect of α-TOC on the secretion of IFN-γ and the population of immunomodulatory cells such as MDSCs and Treg cells, respectively.</div></div><div><h3>Results</h3><div>Our findings revealed that α-TOC significantly induced apoptosis in SW480 cells and promoted the proliferation of PBMCs (<em>P</em> &lt; 0.05). In the co-culture group (PBMC+SW480), α-TOC stimulated PBMC proliferation, increased IFN-γ secretion, and reduced the population of MDSCs (<em>P</em> &lt; 0.05). However, α-TOC did not significantly affect the Treg population<strong>.</strong></div></div><div><h3>Conclusion</h3><div>These results suggest that, in addition to its direct anti-tumor effects, α-TOC also shows immunomodulatory properties in the context of colon cancer in an <em>in vitro</em> model.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153138"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512641","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":"Role and mechanism of METTL3 in fibrosis-associated signaling in CVB3-infected H9c2 cardiomyocytes through the lncRNA MEG3/c-MYC/SMAD2 axis","authors":"Lu Huang ,&nbsp;Li Wang ,&nbsp;Jiaojiao Guo,&nbsp;Shiqian Lu,&nbsp;Qian Zhang,&nbsp;Taiming Liu","doi":"10.1016/j.imbio.2025.153117","DOIUrl":"10.1016/j.imbio.2025.153117","url":null,"abstract":"<div><div>Viral myocarditis (VMC) is an inflammatory disease of the heart muscle caused by viral infection and may lead to myocardial fibrosis. This study aims to investigate the role of METTL3 in myocardial fibrosis in VMC. METTL3 expression was intervened with in VMC cell models, followed by measurement of LDH, CK-MB, and TGF-β1. The expression of METTL3, lncRNA MEG3, c-MYC, SMAD2, Collagen I, Collagen III, and α-SMA was detected by RT-qPCR and Western blot. α-SMA expression was observed by immunofluorescence. MeRIP-qPCR was used to detect m6A levels of MEG3. RNA stability experiments were conducted to determine the residual level of MEG3. The bindings of lncRNA MEG3 to c-MYC and c-MYC to the SMAD2 promoter were analyzed. Results showed that METTL3, c-MYC, and SMAD2 were highly expressed in VMC cell models. METTL3 inhibition increased cell viability and reduced LDH, CK-MB, TGF-β1, Collagen I, Collagen III, and α-SMA. METTL3-mediated m6A modification promoted MEG3 expression, and MEG3 bound to c-MYC and enhanced SMAD2 expression. Overexpression of MEG3 or SMAD2 partially reversed the inhibitory effect of METTL3 on fibrotic-like changes of myocardial cells. In conclusion, METTL3 promotes fibrotic-like changes of myocardial cells in VMC cell models through the lncRNA MEG3/c-MYC/SMAD2 axis via m6A modification.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153117"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119338","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 impact of neutralizing anti-IFN-γ autoantibodies on GBP5 expression and monocyte dysfunction in adult-onset immunodeficiency","authors":"Kanokporn Sornsuwan ,&nbsp;On-anong Juntit ,&nbsp;Kanyarat Thongheang ,&nbsp;Ekkarat Wongsawat ,&nbsp;Chatchai Tayapiwatana ,&nbsp;Umpa Yasamut","doi":"10.1016/j.imbio.2025.153134","DOIUrl":"10.1016/j.imbio.2025.153134","url":null,"abstract":"<div><div>Anti-interferon gamma (IFN-γ) autoantibodies (AIGAs) are linked to opportunistic infections in adult-onset immunodeficiency (AOID). These autoantibodies, particularly those recognizing the C-terminal linear epitope (P128–143) and B27 epitope, block IFN-γ functions in monocytes, contributing to disease. In a retrospective analysis of residual plasma from 45 AOID patients, we confirmed the presence of AIGAs by indirect ELISA and evaluated their capacity to neutralize IFN-γ–induced MHC-II expression. All samples showed neutralizing capability, with varying epitope recognition: 10 samples had AIGAs which recognize both epitopes, 7 had B27 epitope-recognizing AIGAs, 12 had P128–143 epitope-recognizing AIGAs, and 16 had neither. Inhibition levels ranged from 36.5 % to 91.6 %. Five representative samples containing at least B27 epitope-recognizing AIGAs could inhibit guanylate binding protein 5 (GBP5) expression, crucial for pathogen killing. Additionally, high levels of neutralizing AIGAs persisted in patients with active and stable diseases. Overall, the data underscore the relationship between neutralizing AIGA levels, population characteristics, and persistence of AIGAs with monocyte dysfunction and disease outcome.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153134"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444729","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":"Deferoxamine attenuates sepsis-induced liver injury by suppressing ferroptosis","authors":"Haidan Zhang,&nbsp;Hongyao Li,&nbsp;Shixian Liu,&nbsp;Jiahui Zheng,&nbsp;Peiwu Li","doi":"10.1016/j.imbio.2025.153125","DOIUrl":"10.1016/j.imbio.2025.153125","url":null,"abstract":"<div><h3>Background</h3><div>The liver is among the organs most frequently damaged during sepsis, and sepsis-induced liver injury is an independent risk factor for early patient mortality. Ferroptosis has been implicated in sepsis-related organ dysfunction; however, its role in sepsis-induced liver injury remains unclear. This study aimed to investigate the role and underlying mechanisms of ferroptosis in sepsis-associated liver injury.</div></div><div><h3>Methods</h3><div>A rat sepsis model was established in vivo using cecal ligation and puncture (CLP). In vitro, BRL-3A hepatocytes were exposed to lipopolysaccharide (LPS). Deferoxamine (DFO) was administered prior to model induction. Inflammatory cytokine concentrations and the extent of liver injury were assessed. Ferroptosis-related biomarkers, including ferrous ions (Fe²⁺), prostaglandin-endoperoxide synthase 2 (PTGS2), acyl-CoA synthetase long-chain family member 4(ACSL4), malondialdehyde (MDA), glutathione (GSH) and peroxidase 4 (GPX4) were quantified. Lipid peroxidation was measured using the BODIPY 581/591 C11 fluorescent probe. Mitochondrial function was evaluated using electron microscopy and JC-1 fluorescent probe assays.</div></div><div><h3>Results</h3><div>(1) In vivo, DFO treatment was found to alleviate systemic inflammation in septic rats and provided protective effects on the liver. It increased the 7-day survival rate, reduced serum levels of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α), decreased alanine aminotransferase and aspartate aminotransferase levels, and mitigated histopathological damage in liver tissue. In vitro, DFO treatment enhanced the viability of LPS-stimulated BRL-3A hepatocytes. (2) Ferroptosis was observed to be activated in septic rats as well as in LPS-stimulated BRL-3A hepatocytes. DFO reduced the intracellular concentration of ferrous ions and reduced lipid peroxidation as indicated by decreased PTGS2, ACSL4 and MDA. Furthermore, DFO alleviated mitochondrial damage (manifested as reduced mitochondrial volume, decreased membrane density, reduced cristae and outer membrane rupture, etc.), and mitochondrial function was improved. Finally, DFO elevated the levels of GSH and GPX4, which enhanced the antioxidant capacity of hepatocytes.</div></div><div><h3>Conclusion</h3><div>Ferroptosis plays a critical role in the pathogenesis of sepsis-induced liver injury. Targeting the activation of ferroptosis in hepatocytes during sepsis through intervention with DFO may represent a promising therapeutic strategy for the management of this condition.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153125"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258177","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}