Pub Date : 2025-11-01DOI: 10.1016/j.imbio.2025.153136
Kaiwen Wang , Li Guo , Yongqi Zhang , Haiting Yang , Zhenghan Zhao , Hui Du , Jiangfeng Zhao
<div><h3>Objective</h3><div>This study had two primary objectives. First, we aimed to investigate whether differential expression of the chemokine receptor CXCR4 on CD4<sup>+</sup> T lymphocytes could serve as a distinguishing immunological feature between pediatric patients with severe <em>Mycoplasma pneumoniae</em> pneumonia (SMPP) and those with on- Non-severe MPP. Second, we sought to explore the therapeutic potential of the JAK inhibitor Tofacitinib in MPP by examining its effects on CXCR4 pathway modulation, using both clinical observations and experimental validation through an established animal model of MPP.</div></div><div><h3>Methods</h3><div>We conducted a prospective cohort study involving 267 pediatric patients diagnosed with MPP at Jiading District Central Hospital between 2023 and 2024, comprising 42 SMPP cases and 225 Non-severe MPP cases. Baseline clinical and laboratory parameters were systematically collected within 24 h of hospital admission. Flow cytometry was employed to quantify the percentage of CD4<sup>+</sup> T cells expressing CXCR4 (CD4<sup>+</sup>CXCR4<sup>+</sup>) in peripheral blood samples by flow cytometry. For mechanistic investigation, we established a murine model of MPP to evaluate the immunomodulatory effects of Tofacitinib. Treatment groups received either vehicle control or Tofacitinib, after which we analyzed bronchoalveolar lavage fluid (BALF) for inflammatory cytokines (IL-6, IL-8, IP-10, IL-2) and CXCL12 levels via ELISA. Additionally, in vitro experiments were performed using the murine lung epithelial cell line MLE-12 to assess the combined effects of Tofacitinib and a CXCR4 inhibitor on key inflammatory signaling pathways (JAK-STAT and NF-κB) through Western blot analysis.</div></div><div><h3>Results</h3><div>Clinical analysis revealed that children with SMPP had significantly prolonged fever duration (<em>P</em> = 0.0062), extended hospitalization (<em>P</em> < 0.0001), elevated erythrocyte sedimentation rate (<em>P</em> = 0.0161), and higher proportions of CD4<sup>+</sup>CXCR4<sup>+</sup> T lymphocytes (<em>P</em> < 0.0001) compared to Non-severe MPP patients. However, no statistically significant differences were observed in serum levels of C-reactive protein, procalcitonin, or lactate dehydrogenase between the two groups. In the MPP mouse model, BALF analysis demonstrated marked increases in pro-inflammatory cytokines (IL-6, IL-8, IP-10, IL-2) and CXCL12 (<em>P</em> < 0.05), all of which were significantly attenuated by Tofacitinib treatment. Furthermore, Tofacitinib administration reduced CXCR4 expression on CD4<sup>+</sup> T cells in lung tissues. In vitro experiments confirmed that the combination of Tofacitinib and a CXCR4 inhibitor synergistically suppressed activation of the JAK-STAT and NF-κB pathways.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that elevated CD4<sup>+</sup>CXCR4<sup>+</sup> T cell proportions may serve as a predictive biomarker for disease seve
{"title":"Dual-phase study of CD4+CXCR4+ T cells in Mycoplasma pneumoniae pneumonia: clinical correlations in children and therapeutic exploration with tofacitinib in mice","authors":"Kaiwen Wang , Li Guo , Yongqi Zhang , Haiting Yang , Zhenghan Zhao , Hui Du , Jiangfeng Zhao","doi":"10.1016/j.imbio.2025.153136","DOIUrl":"10.1016/j.imbio.2025.153136","url":null,"abstract":"<div><h3>Objective</h3><div>This study had two primary objectives. First, we aimed to investigate whether differential expression of the chemokine receptor CXCR4 on CD4<sup>+</sup> T lymphocytes could serve as a distinguishing immunological feature between pediatric patients with severe <em>Mycoplasma pneumoniae</em> pneumonia (SMPP) and those with on- Non-severe MPP. Second, we sought to explore the therapeutic potential of the JAK inhibitor Tofacitinib in MPP by examining its effects on CXCR4 pathway modulation, using both clinical observations and experimental validation through an established animal model of MPP.</div></div><div><h3>Methods</h3><div>We conducted a prospective cohort study involving 267 pediatric patients diagnosed with MPP at Jiading District Central Hospital between 2023 and 2024, comprising 42 SMPP cases and 225 Non-severe MPP cases. Baseline clinical and laboratory parameters were systematically collected within 24 h of hospital admission. Flow cytometry was employed to quantify the percentage of CD4<sup>+</sup> T cells expressing CXCR4 (CD4<sup>+</sup>CXCR4<sup>+</sup>) in peripheral blood samples by flow cytometry. For mechanistic investigation, we established a murine model of MPP to evaluate the immunomodulatory effects of Tofacitinib. Treatment groups received either vehicle control or Tofacitinib, after which we analyzed bronchoalveolar lavage fluid (BALF) for inflammatory cytokines (IL-6, IL-8, IP-10, IL-2) and CXCL12 levels via ELISA. Additionally, in vitro experiments were performed using the murine lung epithelial cell line MLE-12 to assess the combined effects of Tofacitinib and a CXCR4 inhibitor on key inflammatory signaling pathways (JAK-STAT and NF-κB) through Western blot analysis.</div></div><div><h3>Results</h3><div>Clinical analysis revealed that children with SMPP had significantly prolonged fever duration (<em>P</em> = 0.0062), extended hospitalization (<em>P</em> < 0.0001), elevated erythrocyte sedimentation rate (<em>P</em> = 0.0161), and higher proportions of CD4<sup>+</sup>CXCR4<sup>+</sup> T lymphocytes (<em>P</em> < 0.0001) compared to Non-severe MPP patients. However, no statistically significant differences were observed in serum levels of C-reactive protein, procalcitonin, or lactate dehydrogenase between the two groups. In the MPP mouse model, BALF analysis demonstrated marked increases in pro-inflammatory cytokines (IL-6, IL-8, IP-10, IL-2) and CXCL12 (<em>P</em> < 0.05), all of which were significantly attenuated by Tofacitinib treatment. Furthermore, Tofacitinib administration reduced CXCR4 expression on CD4<sup>+</sup> T cells in lung tissues. In vitro experiments confirmed that the combination of Tofacitinib and a CXCR4 inhibitor synergistically suppressed activation of the JAK-STAT and NF-κB pathways.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that elevated CD4<sup>+</sup>CXCR4<sup>+</sup> T cell proportions may serve as a predictive biomarker for disease seve","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153136"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451604","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}
Klebsiella pneumoniae (Kp) infection has high global complication and mortality rate. Programmed cell death ligand 1 (PD-L1) is important for immune evasion in tumorigenesis, however, with unclear mechanism in Kp infection. This study aims to explore the role and potential mechanisms of PD-L1 in Kp-infected mouse mononuclear macrophages RAW264.7 cells. Here, RAW264.7 cells were infected with classical Kp (cKp) and highly virulent Kp (hvKp), and transfected with PD-L1 knockdown. Subsequently, to investigate the effect of PD-L1 on the activation of CD4+ T cells, a co-culture system of RAW264.7 and CD4+ T cells was established. In RAW264.7 cells infected with Kp, PD-L1 knockdown reduced apoptosis and necrosis, with lower Bax, Cleaved Caspase 3, p-RIPK1/RIPK1, p-RIPK3/RIPK3, and p-MLKL/MLKL expression. Meanwhile, phagocytic activity and phagocytic index were enhanced, with increased Kp count. Furthermore, PD-L1 knockdown led to the activation of RAW264.7 cells, which participated in immune regulation, accompanied by higher levels of IL-1β, IL-6, TNF-α, MHC II, CD80, and CD86. Following co-culture of RAW264.7 and CD4+ T cells, PD-L1 knockdown reversed the effect of Kp infection to promote CD4+ T cell activation, as evidenced by decreased apoptosis and elevated IFN-γ, TNF-α, and IL-2 levels. This result preliminarily demonstrated that PD-L1 expression may be involved in antigen presentation in RAW264.7 cells with Kp infection. In conclusion, in Kp-infected RAW264.7 cells, PD-L1 mediates the increased apoptosis, necrosis, inflammatory responses, and CD4+ T cell activation, as well as inhibition of phagocytosis, and may be involved in antigen presentation, offering new therapeutic targets for Kp infection.
{"title":"Programmed cell death ligand 1 mediates antigen presentation, apoptosis, necrosis, and inflammatory response in Klebsiella pneumoniae-infected macrophages","authors":"Xiaoya Zheng , Weihong Tang , Qiaoqiao Tang , Qiao Wu , Jiancong Shan","doi":"10.1016/j.imbio.2025.153133","DOIUrl":"10.1016/j.imbio.2025.153133","url":null,"abstract":"<div><div><em>Klebsiella pneumoniae</em> (Kp) infection has high global complication and mortality rate. Programmed cell death ligand 1 (PD-L1) is important for immune evasion in tumorigenesis, however, with unclear mechanism in Kp infection. This study aims to explore the role and potential mechanisms of PD-L1 in Kp-infected mouse mononuclear macrophages RAW264.7 cells. Here, RAW264.7 cells were infected with classical Kp (cKp) and highly virulent Kp (hvKp), and transfected with PD-L1 knockdown. Subsequently, to investigate the effect of PD-L1 on the activation of CD4<sup>+</sup> T cells, a co-culture system of RAW264.7 and CD4<sup>+</sup> T cells was established. In RAW264.7 cells infected with Kp, PD-L1 knockdown reduced apoptosis and necrosis, with lower Bax, Cleaved Caspase 3, p-RIPK1/RIPK1, p-RIPK3/RIPK3, and p-MLKL/MLKL expression. Meanwhile, phagocytic activity and phagocytic index were enhanced, with increased Kp count. Furthermore, PD-L1 knockdown led to the activation of RAW264.7 cells, which participated in immune regulation, accompanied by higher levels of IL-1β, IL-6, TNF-α, MHC II, CD80, and CD86. Following co-culture of RAW264.7 and CD4<sup>+</sup> T cells, PD-L1 knockdown reversed the effect of Kp infection to promote CD4<sup>+</sup> T cell activation, as evidenced by decreased apoptosis and elevated IFN-γ, TNF-α, and IL-2 levels. This result preliminarily demonstrated that PD-L1 expression may be involved in antigen presentation in RAW264.7 cells with Kp infection. In conclusion, in Kp-infected RAW264.7 cells, PD-L1 mediates the increased apoptosis, necrosis, inflammatory responses, and CD4<sup>+</sup> T cell activation, as well as inhibition of phagocytosis, and may be involved in antigen presentation, offering new therapeutic targets for Kp infection.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153133"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416596","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}
Pub Date : 2025-11-01DOI: 10.1016/j.imbio.2025.153131
Soha M. Hussien
Gamma radiation (γR) influences cytokine regulation, with high doses (HD) producing marked biological effects under both controlled and accidental exposure scenarios. This study investigates the immunological responses to γR at doses of 2, 3, and 5 Gray (Gy) by examining T-cell receptor (TCR) mRNA expression, serum levels of Interleukin-10 (IL-10), Transforming Growth Factor-β (TGF-β), and Nitric Oxide (NO), as well as hematological parameters. These effects were compared between days 1 and 4 post-irradiation. Forty-eight male rats were randomly allocated into eight groups (six rats each), with Groups I and V serving as non-irradiated controls. Groups II–IV and Groups VI–VIII received whole-body γ-irradiation at doses of 2, 3, and 5 Gy, respectively. On days 1 and 4 after exposure, reverse transcription quantitative PCR (RT-qPCR) and standard hematological techniques were employed to assess gene expression, cytokine levels, hemoglobin concentration, hematocrit percentage, blood cell counts, and organ weights. This study demonstrates that high-dose γ-radiation (2–5 Gy) significantly (P < 0.05) increases TCR mRNA expression, hematological indices, and lymphoid organ weights, while IL-10 declines (P < 0.05), and TGF-β and nitric oxide levels are markedly elevated. Despite these observations, the null hypothesis was accepted for both time points (P > 0.05), indicating that there were no statistically significant differences across specific parameters. The observed inverse correlation between radiation exposure and lymphoid organ development supports the role of γR in altering immune-regulatory cytokines. Ultimately, higher γR doses tend to produce more pronounced immunological alterations, regardless of the intent of exposure.
{"title":"The Impacts of Acute High-Level Gamma Radiation Exposure on immunological parameters in the blood of rats","authors":"Soha M. Hussien","doi":"10.1016/j.imbio.2025.153131","DOIUrl":"10.1016/j.imbio.2025.153131","url":null,"abstract":"<div><div>Gamma radiation (γR) influences cytokine regulation, with high doses (HD) producing marked biological effects under both controlled and accidental exposure scenarios. This study investigates the immunological responses to γR at doses of 2, 3, and 5 Gray (Gy) by examining T-cell receptor (TCR) mRNA expression, serum levels of Interleukin-10 (IL-10), Transforming Growth Factor-β (TGF-β), and Nitric Oxide (NO), as well as hematological parameters. These effects were compared between days 1 and 4 post-irradiation. Forty-eight male rats were randomly allocated into eight groups (six rats each), with Groups I and V serving as non-irradiated controls. Groups II–IV and Groups VI–VIII received whole-body γ-irradiation at doses of 2, 3, and 5 Gy, respectively. On days 1 and 4 after exposure, reverse transcription quantitative PCR (RT-qPCR) and standard hematological techniques were employed to assess gene expression, cytokine levels, hemoglobin concentration, hematocrit percentage, blood cell counts, and organ weights. This study demonstrates that high-dose γ-radiation (2–5 Gy) significantly (<em>P</em> < 0.05) increases TCR mRNA expression, hematological indices, and lymphoid organ weights, while IL-10 declines (P < 0.05), and TGF-β and nitric oxide levels are markedly elevated. Despite these observations, the null hypothesis was accepted for both time points (<em>P</em> > 0.05), indicating that there were no statistically significant differences across specific parameters. The observed inverse correlation between radiation exposure and lymphoid organ development supports the role of γR in altering immune-regulatory cytokines. Ultimately, higher γR doses tend to produce more pronounced immunological alterations, regardless of the intent of exposure.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153131"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145389066","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}
Pub Date : 2025-11-01DOI: 10.1016/j.imbio.2025.153141
Zilun Lei , Tong Mou , Hao Chai , Qiang Liu , Ziqi Zhang
Recent research has underscored NLRX1's role in modulating hepatic immune responses. However, its function in Kupffer cells (KCs) during acute rejection (AR) post-liver transplantation is not well elucidated, and the mechanisms driving hepatic AR require deeper investigation. Our study found that NLRX1 expression was markedly reduced in hepatic AR models, both in vivo and in vitro. NLRX1 overexpression significantly dampened the activation of the MAPK and IKK pathways, leading to decreased cytokine secretion and mitigated liver damage and apoptosis. In contrast, NLRX1 downregulation intensified these adverse effects. Further mechanistic studies indicated that NLRX1's interaction with TRAF6 was crucial for its anti-inflammatory effects, which could be nullified by TRAF6 blockade. Moreover, in vitro assays showed that NLRX1 could drive KCs to transition from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype via the PI3K/Akt pathway. Overall, our results imply that targeting NLRX1 in conjunction with mTOR could be a viable approach to prevent hepatic AR, and suggest potential cross-talk between TRAF6-dependent inflammatory suppression and PI3K/Akt-mediated M2 polarization that requires further validation.
{"title":"NLRX1 as a novel therapeutic target: TRAF6-dependent inhibition of acute rejection in rat liver transplantation","authors":"Zilun Lei , Tong Mou , Hao Chai , Qiang Liu , Ziqi Zhang","doi":"10.1016/j.imbio.2025.153141","DOIUrl":"10.1016/j.imbio.2025.153141","url":null,"abstract":"<div><div>Recent research has underscored NLRX1's role in modulating hepatic immune responses. However, its function in Kupffer cells (KCs) during acute rejection (AR) post-liver transplantation is not well elucidated, and the mechanisms driving hepatic AR require deeper investigation. Our study found that NLRX1 expression was markedly reduced in hepatic AR models, both in vivo and in vitro. NLRX1 overexpression significantly dampened the activation of the MAPK and IKK pathways, leading to decreased cytokine secretion and mitigated liver damage and apoptosis. In contrast, NLRX1 downregulation intensified these adverse effects. Further mechanistic studies indicated that NLRX1's interaction with TRAF6 was crucial for its anti-inflammatory effects, which could be nullified by TRAF6 blockade. Moreover, in vitro assays showed that NLRX1 could drive KCs to transition from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype via the PI3K/Akt pathway. Overall, our results imply that targeting NLRX1 in conjunction with mTOR could be a viable approach to prevent hepatic AR, and suggest potential cross-talk between TRAF6-dependent inflammatory suppression and PI3K/Akt-mediated M2 polarization that requires further validation.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153141"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563741","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}
Pub Date : 2025-11-01DOI: 10.1016/j.imbio.2025.153132
Yan Zhang , Wen-yan Yu , Zhi-xing Ma , Lin Kang , Qiao-ling Yao , Zhan Sun , Xiao-juan Ma
Objective
To investigate the role of IL33/HIF1α/VEGF in lung tissue injury caused by intermittent hypoxia (IH) model in mice, and to reveal its possible mechanisms.
Methods
Forty male C57BL/6 J mice were randomly divided into the room air (RA) group, the intermittent hypoxia (IH) group, the intermittent hypoxia + IL33 neutralizing antibody (IH-antiIL33) group, the intermittent hypoxia + IL33 recombinant mouse protein (IH-rmIL33) group and the intermittent hypoxia + IgG negative control (IH-IgG) group. The following parameters were evaluated in all mouse groups:pulmonary function and lung tissue histology and molecular profiles (mRNA/protein levels of IL-33, HIF-1α, and VEGF, along with inflammatory factor concentrations).
Results
Pulmonary function tests demonstrated significantly aggravated airway obstruction in the IH group compared to the RA group (P < 0.01). IL-33 intervention primarily affected small airway resistance and expiratory function in IH mice (P < 0.05). Histological staining revealed that rmIL-33 exacerbated IH-induced lung tissue injury and fibrosis (P < 0.01), while anti-IL-33 intervention showed alleviating effects. Molecular analyses confirmed upregulation of IL-33, HIF-1α, VEGF, and inflammatory factors (IL-6, TNF-α) in IH group lung tissues (P < 0.01). Exogenous IL-33 further enhanced these expression levels (P < 0.05), whereas anti-IL-33 intervention effectively suppressed them (P < 0.01). IHC results indicated significant alterations in IL-33 protein expression following interventions (P < 0.001). STRING database predictions suggested potential indirect interaction between IL-33 and HIF-1α via IL1R1.
Conclusion
It is suggested that IL33/HIF1α/VEGF may be involved in the pathogenesis of lung injury due to IH through multiple mechanisms.
目的：探讨il - 33/HIF1α/VEGF在小鼠间歇性缺氧（IH）模型肺组织损伤中的作用，并探讨其可能的机制。方法：将40只雄性C57BL/ 6j小鼠随机分为室内空气（RA）组、间歇缺氧（IH）组、间歇缺氧+ il - 33中和抗体（IH- antiil33）组、间歇缺氧+ il - 33重组小鼠蛋白（IH- rmil33）组和间歇缺氧+ IgG阴性对照（IH-IgG）组。在所有小鼠组中评估以下参数：肺功能、肺组织组织学和分子谱（IL-33、HIF-1α和VEGF的mRNA/蛋白水平以及炎症因子浓度）。结果：肺功能检查显示IH组气道阻塞较RA组明显加重(P)。结论：提示IL33/HIF1α/VEGF可能通过多种机制参与IH肺损伤的发生。
{"title":"Role of IL33/HIF1α/VEGF in intermittent hypoxia-induced lung injury","authors":"Yan Zhang , Wen-yan Yu , Zhi-xing Ma , Lin Kang , Qiao-ling Yao , Zhan Sun , Xiao-juan Ma","doi":"10.1016/j.imbio.2025.153132","DOIUrl":"10.1016/j.imbio.2025.153132","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the role of IL33/HIF1α/VEGF in lung tissue injury caused by intermittent hypoxia (IH) model in mice, and to reveal its possible mechanisms.</div></div><div><h3>Methods</h3><div>Forty male C57BL/6 J mice were randomly divided into the room air (RA) group, the intermittent hypoxia (IH) group, the intermittent hypoxia + IL33 neutralizing antibody (IH-antiIL33) group, the intermittent hypoxia + IL33 recombinant mouse protein (IH-rmIL33) group and the intermittent hypoxia + IgG negative control (IH-IgG) group. The following parameters were evaluated in all mouse groups:pulmonary function and lung tissue histology and molecular profiles (mRNA/protein levels of IL-33, HIF-1α, and VEGF, along with inflammatory factor concentrations).</div></div><div><h3>Results</h3><div>Pulmonary function tests demonstrated significantly aggravated airway obstruction in the IH group compared to the RA group (<em>P</em> < 0.01). IL-33 intervention primarily affected small airway resistance and expiratory function in IH mice (<em>P</em> < 0.05). Histological staining revealed that rmIL-33 exacerbated IH-induced lung tissue injury and fibrosis (<em>P</em> < 0.01), while anti-IL-33 intervention showed alleviating effects. Molecular analyses confirmed upregulation of IL-33, HIF-1α, VEGF, and inflammatory factors (IL-6, TNF-α) in IH group lung tissues (<em>P</em> < 0.01). Exogenous IL-33 further enhanced these expression levels (<em>P</em> < 0.05), whereas anti-IL-33 intervention effectively suppressed them (P < 0.01). IHC results indicated significant alterations in IL-33 protein expression following interventions (<em>P</em> < 0.001). STRING database predictions suggested potential indirect interaction between IL-33 and HIF-1α via IL1R1.</div></div><div><h3>Conclusion</h3><div>It is suggested that IL33/HIF1α/VEGF may be involved in the pathogenesis of lung injury due to IH through multiple mechanisms.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153132"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503650","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}
Pub Date : 2025-11-01DOI: 10.1016/j.imbio.2025.153143
YaLing Xu , WenNa Li , Yuan Li , Xin Li , XinNa Li , Bo Wang
Purpose
OX40 is a typical member of the co-stimulatory molecule family. The signals generated by its binding to OX40L have a synergistic effect, regulating T cell proliferation, differentiation, and influencing cytokine secretion. This study aimed to evaluate the role of OX40 in regulating the progression of liver fibrosis induced by CCL4-induced inflammation.
Patients and methods
OX40 expression levels in tissue samples from individuals with liver fibrosis and healthy controls were analyzed using the Gene Expression Omnibus (GEO) database. Furthermore, a murine model of liver fibrosis was established by administering CCL4 through continuous intraperitoneal injections over an 8-week period. The extent of liver fibrosis was evaluated through histopathological staining. Flow cytometry was employed to identify CD4+ T lymphocytes and to track the dynamic expression of OX40 on these cells in splenic samples throughout the progression of liver fibrosis.
Results
Database analysis revealed that OX40 expression was significantly upregulated in liver fibrosis tissues compared to corresponding normal tissues. Following CCL4 induction, there was a marked increase in alanine transaminase (ALT) and aspartate aminotransferase (AST) levels. Hematoxylin and eosin (HE) staining, along with Masson's trichrome staining, highlighted the presence of damaged tissue architecture in the murine models. Additionally, the upregulation of OX40 expression in liver fibrosis showed a positive correlation with elevated levels of alpha-smooth muscle actin (α-SMA) and the production of collagen fibers. ELISA results indicate that interference with the OX40 molecule can affect cytokine expression. Blocking the OX40-OX40L signaling pathway can, to some extent, regulate the direction of immune polarization.
Conclusion
These results suggest that the OX40 molecule may be involved in the immune imbalance occurring during the development and progression of liver fibrosis, thereby contributing to hepatic tissue injury.
{"title":"The expression of OX40 in CD4+ T cells and its association with hepatic fibrosis injury","authors":"YaLing Xu , WenNa Li , Yuan Li , Xin Li , XinNa Li , Bo Wang","doi":"10.1016/j.imbio.2025.153143","DOIUrl":"10.1016/j.imbio.2025.153143","url":null,"abstract":"<div><h3>Purpose</h3><div>OX40 is a typical member of the co-stimulatory molecule family. The signals generated by its binding to OX40L have a synergistic effect, regulating T cell proliferation, differentiation, and influencing cytokine secretion. This study aimed to evaluate the role of OX40 in regulating the progression of liver fibrosis induced by CCL4-induced inflammation.</div></div><div><h3>Patients and methods</h3><div>OX40 expression levels in tissue samples from individuals with liver fibrosis and healthy controls were analyzed using the Gene Expression Omnibus (GEO) database. Furthermore, a murine model of liver fibrosis was established by administering CCL4 through continuous intraperitoneal injections over an 8-week period. The extent of liver fibrosis was evaluated through histopathological staining. Flow cytometry was employed to identify CD4+ T lymphocytes and to track the dynamic expression of OX40 on these cells in splenic samples throughout the progression of liver fibrosis.</div></div><div><h3>Results</h3><div>Database analysis revealed that OX40 expression was significantly upregulated in liver fibrosis tissues compared to corresponding normal tissues. Following CCL4 induction, there was a marked increase in alanine transaminase (ALT) and aspartate aminotransferase (AST) levels. Hematoxylin and eosin (HE) staining, along with Masson's trichrome staining, highlighted the presence of damaged tissue architecture in the murine models. Additionally, the upregulation of OX40 expression in liver fibrosis showed a positive correlation with elevated levels of alpha-smooth muscle actin (α-SMA) and the production of collagen fibers. ELISA results indicate that interference with the OX40 molecule can affect cytokine expression. Blocking the OX40-OX40L signaling pathway can, to some extent, regulate the direction of immune polarization.</div></div><div><h3>Conclusion</h3><div>These results suggest that the OX40 molecule may be involved in the immune imbalance occurring during the development and progression of liver fibrosis, thereby contributing to hepatic tissue injury.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153143"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614742","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}
Pub Date : 2025-10-24DOI: 10.1016/j.imbio.2025.153129
Ai Cui , Wenyan Fan , Tengyi Huang , Xinyi Li , Wenjing Xiong , Yongni Wang , Yu Chen
Background
Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women worldwide. Due to its high metastasis rate and poor prognosis, CRC is the leading cause of cancer-related deaths worldwide.
Materials and methods
Combined gene therapy is a promising treatment that can be used to alter the genes involved in cancer genesis and development. This report describes the use of a eukaryotic co-expression plasmid that encodes both STAT3 siRNAs (si-STAT3) and endostatin for the treatment of CRC homografts in C57BL/6 mice, with attenuated Salmonella typhimurium (S. typhimurium) used to facilitate efficient delivery of the plasmid.
Results
In this study, single treatment with either si-STAT3 or endostatin showed antitumor effects in the CRC homograft model, and the co-expression treatment had more significant antitumor effects. Not only did the co-expressed plasmids alter the STAT3 and endostatin expression, this treatment also down-regulated MMP2 and cyclin D1 expression and up-regulated caspase 3 expression. The levels of CD4+ T cells, CD8+ T cells, NK cells, and CD4+CD25+Foxp3+ regulatory T cells (Treg cells) were also affected by the combined treatment. In addition, the combined therapy altered cytokine expression, enhancing antitumor immunity.
Conclusion
The combined gene therapy used in this study additively inhibited colorectal homograft tumor growth.
{"title":"Attenuated S. typhimurium delivery of STAT3-siRNA and endostatin co-expression plasmids for immune and angiogenesis modulation in colorectal cancer","authors":"Ai Cui , Wenyan Fan , Tengyi Huang , Xinyi Li , Wenjing Xiong , Yongni Wang , Yu Chen","doi":"10.1016/j.imbio.2025.153129","DOIUrl":"10.1016/j.imbio.2025.153129","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women worldwide. Due to its high metastasis rate and poor prognosis, CRC is the leading cause of cancer-related deaths worldwide.</div></div><div><h3>Materials and methods</h3><div>Combined gene therapy is a promising treatment that can be used to alter the genes involved in cancer genesis and development. This report describes the use of a eukaryotic co-expression plasmid that encodes both STAT3 siRNAs (si-STAT3) and endostatin for the treatment of CRC homografts in C57BL/6 mice, with attenuated <em>Salmonella typhimurium</em> (<em>S. typhimurium</em>) used to facilitate efficient delivery of the plasmid.</div></div><div><h3>Results</h3><div>In this study, single treatment with either si-STAT3 or endostatin showed antitumor effects in the CRC homograft model, and the co-expression treatment had more significant antitumor effects. Not only did the co-expressed plasmids alter the STAT3 and endostatin expression, this treatment also down-regulated MMP2 and cyclin D1 expression and up-regulated caspase 3 expression. The levels of CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, NK cells, and CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> regulatory T cells (Treg cells) were also affected by the combined treatment. In addition, the combined therapy altered cytokine expression, enhancing antitumor immunity.</div></div><div><h3>Conclusion</h3><div>The combined gene therapy used in this study additively inhibited colorectal homograft tumor growth.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153129"},"PeriodicalIF":2.3,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358909","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}
Pub Date : 2025-10-22DOI: 10.1016/j.imbio.2025.153130
Agnieszka Tarnowska , Andrzej Wiśniewski , Julia Burnos , Paweł Radwan , Kazimierz Chorobik , Michał Radwan , Karolina Piekarska , Andrzej Malinowski , Jacek R. Wilczyński , Izabela Nowak
Background
Human leukocyte antigen (HLA)-E as a non-classical HLA class I molecule interacting with NK and T cell receptors may activate or inhibit immune responses. These reactions can impact reproductive success because HLA-E is expressed by trophoblast cells. In this study, we investigated rs1264457 A/G HLA-E polymorphism in couples with reproductive failures such as recurrent implantation failure (RIF) after in vitro fertilization (IVF), recurrent spontaneous abortion (RSA), and sporadic spontaneous abortion (SSA) after natural conception. Furthermore, we investigated the role of the soluble HLA-E isoform (sHLA-E) in women's plasma and seminal plasma of men participating in IVF procedures.
Methods
We used real-time PCR with a TaqMan probe to study the rs1264457 polymorphism, which represents a much better-known HLA-E*01:01/HLA-E*01:03 dimorphism, and ELISA test to measure the soluble HLA-E isoform.
Results
Our study indicates that the rs1264457 A/G polymorphism did not influence female infertility or susceptibility to RIF and RSA. However, we noticed that HLA-E*0101 homozygotic men were more susceptible to having severe, very severe oligozoospermia or azoospermia (p = 0.013, OR = 1.70). Moreover, we found a higher concentration of sHLA-E in IVF patients than in control women (p < 0.0001/pcorr. = 0.0024). In turn, a lower level of sHLA-E in semen plasma was associated with fewer sperm cells (p < 0.0001).
Conclusions
HLA-E*0101 homozygosity and lower levels of soluble HLA-E in men's ejaculate are associated with reduced sperm count and may impact male fertility.
人类白细胞抗原(HLA)-E作为一种非经典HLA I类分子与NK和T细胞受体相互作用，可激活或抑制免疫反应。这些反应可以影响生殖成功，因为HLA-E是由滋养细胞表达的。在本研究中，我们研究了rs1264457 A/G HLA-E多态性在体外受精（IVF）后复发性着床失败（RIF）、自然受孕后复发性自然流产（RSA）和散发性自然流产（SSA）等生殖失败夫妇中的多态性。此外，我们还研究了可溶性HLA-E异构体（sHLA-E）在参与体外受精程序的女性血浆和男性精浆中的作用。方法采用实时荧光定量PCR和TaqMan探针检测HLA-E*01:01/HLA-E*01:03双态rs1264457多态性，ELISA检测可溶性HLA-E异构体。结果rs1264457 A/G多态性不影响女性不育或对RIF和RSA的易感性。然而，我们注意到HLA-E*0101纯合子男性更容易发生严重、极严重的少精症或无精症（p = 0.013, or = 1.70）。此外，我们发现体外受精患者的sHLA-E浓度高于对照组（p < 0.0001/pcorr）。= 0.0024)。反过来，精液血浆中较低水平的sHLA-E与较少的精子细胞相关（p < 0.0001）。结论男性射精中shla - e *0101纯合性和可溶性HLA-E水平降低与精子数量减少有关，可能影响男性生育能力。
{"title":"The role of HLA-E polymorphism and soluble HLA-E isoform in recurrent reproductive failures and male infertility","authors":"Agnieszka Tarnowska , Andrzej Wiśniewski , Julia Burnos , Paweł Radwan , Kazimierz Chorobik , Michał Radwan , Karolina Piekarska , Andrzej Malinowski , Jacek R. Wilczyński , Izabela Nowak","doi":"10.1016/j.imbio.2025.153130","DOIUrl":"10.1016/j.imbio.2025.153130","url":null,"abstract":"<div><h3>Background</h3><div>Human leukocyte antigen (HLA)-E as a non-classical HLA class I molecule interacting with NK and T cell receptors may activate or inhibit immune responses. These reactions can impact reproductive success because HLA-E is expressed by trophoblast cells. In this study, we investigated rs1264457 A/G HLA-E polymorphism in couples with reproductive failures such as recurrent implantation failure (RIF) after in vitro fertilization (IVF), recurrent spontaneous abortion (RSA), and sporadic spontaneous abortion (SSA) after natural conception. Furthermore, we investigated the role of the soluble HLA-E isoform (sHLA-E) in women's plasma and seminal plasma of men participating in IVF procedures.</div></div><div><h3>Methods</h3><div>We used real-time PCR with a TaqMan probe to study the rs1264457 polymorphism, which represents a much better-known <em>HLA-E*01:01/HLA-E*01:03</em> dimorphism, and ELISA test to measure the soluble HLA-E isoform.</div></div><div><h3>Results</h3><div>Our study indicates that the rs1264457 A/G polymorphism did not influence female infertility or susceptibility to RIF and RSA. However, we noticed that <em>HLA-E*0101</em> homozygotic men were more susceptible to having severe, very severe oligozoospermia or azoospermia (<em>p</em> = 0.013, OR = 1.70). Moreover, we found a higher concentration of sHLA-E in IVF patients than in control women (<em>p</em> < 0.0001/p<sub>corr.</sub> = 0.0024). In turn, a lower level of sHLA-E in semen plasma was associated with fewer sperm cells (p < 0.0001).</div></div><div><h3>Conclusions</h3><div><em>HLA-E*0101</em> homozygosity and lower levels of soluble HLA-E in men's ejaculate are associated with reduced sperm count and may impact male fertility.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153130"},"PeriodicalIF":2.3,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358094","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}
Pub Date : 2025-10-20DOI: 10.1016/j.imbio.2025.153128
Richard F. Kraus , Nina Doblinger , Michael A. Gruber , Maria S. Wagner , Johanna Rosenberger
Background
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.
Methods
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.
Results
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.
Conclusion
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.
{"title":"Sexual dimorphism in neutrophil function: Unveiling the discriminative nature of male and female neutrophils","authors":"Richard F. Kraus , Nina Doblinger , Michael A. Gruber , Maria S. Wagner , 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":"2025-10-20","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}
Pub Date : 2025-10-03DOI: 10.1016/j.imbio.2025.153125
Haidan Zhang, Hongyao Li, Shixian Liu, Jiahui Zheng, Peiwu Li
Background
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.
Methods
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.
Results
(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.
Conclusion
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.
{"title":"Deferoxamine attenuates sepsis-induced liver injury by suppressing ferroptosis","authors":"Haidan Zhang, Hongyao Li, Shixian Liu, Jiahui Zheng, 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 (Fe<sup>2+</sup>), 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":"2025-10-03","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}
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