Immunobiology最新文献

{"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}

{"title":"The role of HLA-E polymorphism and soluble HLA-E isoform in recurrent reproductive failures and male infertility","authors":"Agnieszka Tarnowska ,&nbsp;Andrzej Wiśniewski ,&nbsp;Julia Burnos ,&nbsp;Paweł Radwan ,&nbsp;Kazimierz Chorobik ,&nbsp;Michał Radwan ,&nbsp;Karolina Piekarska ,&nbsp;Andrzej Malinowski ,&nbsp;Jacek R. Wilczyński ,&nbsp;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> &lt; 0.0001/p_corr. = 0.0024). In turn, a lower level of sHLA-E in semen plasma was associated with fewer sperm cells (p &lt; 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":"2025-11-01","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}

{"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 ,&nbsp;Li Guo ,&nbsp;Yongqi Zhang ,&nbsp;Haiting Yang ,&nbsp;Zhenghan Zhao ,&nbsp;Hui Du ,&nbsp;Jiangfeng Zhao","doi":"10.1016/j.imbio.2025.153136","DOIUrl":"10.1016/j.imbio.2025.153136","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;This study had two primary objectives. First, we aimed to investigate whether differential expression of the chemokine receptor CXCR4 on CD4&lt;sup&gt;+&lt;/sup&gt; T lymphocytes could serve as a distinguishing immunological feature between pediatric patients with severe &lt;em&gt;Mycoplasma pneumoniae&lt;/em&gt; 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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;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&lt;sup&gt;+&lt;/sup&gt; T cells expressing CXCR4 (CD4&lt;sup&gt;+&lt;/sup&gt;CXCR4&lt;sup&gt;+&lt;/sup&gt;) 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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Clinical analysis revealed that children with SMPP had significantly prolonged fever duration (&lt;em&gt;P&lt;/em&gt; = 0.0062), extended hospitalization (&lt;em&gt;P&lt;/em&gt; &lt; 0.0001), elevated erythrocyte sedimentation rate (&lt;em&gt;P&lt;/em&gt; = 0.0161), and higher proportions of CD4&lt;sup&gt;+&lt;/sup&gt;CXCR4&lt;sup&gt;+&lt;/sup&gt; T lymphocytes (&lt;em&gt;P&lt;/em&gt; &lt; 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 (&lt;em&gt;P&lt;/em&gt; &lt; 0.05), all of which were significantly attenuated by Tofacitinib treatment. Furthermore, Tofacitinib administration reduced CXCR4 expression on CD4&lt;sup&gt;+&lt;/sup&gt; 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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Our findings indicate that elevated CD4&lt;sup&gt;+&lt;/sup&gt;CXCR4&lt;sup&gt;+&lt;/sup&gt; 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}

{"title":"Complement at the crossroads of inflammation and metabolism: implications for diabetes and metabolic functions","authors":"Vaishnavi Dandavate,&nbsp;Anna M. Blom,&nbsp;Ben C. King","doi":"10.1016/j.imbio.2025.153113","DOIUrl":"10.1016/j.imbio.2025.153113","url":null,"abstract":"<div><div>Diabetes is a growing global problem, with hundreds of millions of people living with the disease worldwide. Diabetes can be divided into two major subtypes, autoimmune type 1 diabetes (T1D), and type 2 diabetes (T2D), which has stronger causal links in obesity, lifestyle, and age. Although immunity and inflammation are clearly defined in T1D, it is also understood that inflammation has a role in metabolic dysregulation in T2D, inducing insulin resistance as well as affecting β-cell function, survival, and therefore insulin secretion. Cytokines and other inflammatory mediators can affect function of cells important for metabolism, most studied in adipose tissue, muscle, and pancreatic islets. Similarly, evidence shows that complement can also have positive roles in metabolic homeostasis in adipose tissue and pancreatic islets. This review will give an introduction to this field, with focus on established and emerging roles of the complement system, an arm of humoral innate immunity that has been found to have roles in metabolic homeostasis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153113"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085992","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":"A novel approach to poliovirus vaccine neurovirulence testing: development of an enhanced 4-level scoring system","authors":"Xi Wang ,&nbsp;Yunguang Hu ,&nbsp;Anguo Yin ,&nbsp;Changxu Chen ,&nbsp;Hong Xiang ,&nbsp;Li Wang ,&nbsp;Bochuan Liu ,&nbsp;Yuan Tian ,&nbsp;Yu Gao ,&nbsp;Mingrun Zhang ,&nbsp;Yan Li ,&nbsp;Yina Cun ,&nbsp;Jian Zhou","doi":"10.1016/j.imbio.2025.153121","DOIUrl":"10.1016/j.imbio.2025.153121","url":null,"abstract":"<div><div>The ongoing promotion and administration of vaccines play a critical role in the global effort to eradicate poliovirus. The Monkey Neurovirulence Test (MNVT) is an essential method for evaluating the neurovirulence of viruses in both the Oral Attenuated Live Poliovirus Vaccine (OPV) and the Sabin Inactivated Poliovirus Vaccine (sIPV) to ensure they meet required safety standards. The “4-level scoring method” recommended by the World Health Organization (WHO) has served as a key pathological evaluation criterion in this test. However, its lack of scoring granularity often leads to subjective interpretation discrepancies among evaluators, which compromises the consistency and reliability of the MNVT results. To address these limitations, we have mapped the primary neuronal nuclei in monkey tissue sections and analyzed viral-induced damage distribution. As a result, we developed an Enhanced 4-Level Scoring System (integrating precise anatomical mapping and quantitative lesion analysis), which minimizes evaluator bias and significantly improves scoring stability and consistency.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153121"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232448","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":"Programmed cell death ligand 1 mediates antigen presentation, apoptosis, necrosis, and inflammatory response in Klebsiella pneumoniae-infected macrophages","authors":"Xiaoya Zheng ,&nbsp;Weihong Tang ,&nbsp;Qiaoqiao Tang ,&nbsp;Qiao Wu ,&nbsp;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⁺ 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.</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}

{"title":"The grand escape – how pathogens outsmart the human complement system","authors":"A.A. Nowacka ,&nbsp;L. Sordo Vieira ,&nbsp;V. Petr ,&nbsp;B. Fageräng ,&nbsp;R. Würzner ,&nbsp;M. Ohms","doi":"10.1016/j.imbio.2025.153126","DOIUrl":"10.1016/j.imbio.2025.153126","url":null,"abstract":"<div><div>Infectious diseases remain a significant cause of mortality and morbidity worldwide. Complement is a critical component in the defense against pathogens and despite their great differences, viruses, bacteria, fungi, and protists have all developed similar mechanisms of evasion from the human complement system. Using examples from four microbial groups (viruses, bacteria, fungi and protists), this review expands on examples of these different mechanisms of evasion. The mechanisms are grouped as (A) avoidance of recognition, (B) avoidance of eradication, (C) avoidance of activation and function, or (D) use of the complement proteins for entry into the host, in accordance with the classification initially proposed in 1999. Furthermore, this review will expand on novel descriptions of complement evasion, for example involving intracellular complement. Taken toge complement evasion is an essential tool used by pathogens not only in a defensive manner, protecting the pathogen from the host, but can also employed in an aggressive manner to aid the invasion of the host. Understanding these mechanisms has already influenced diagnostic and therapeutic tools, including vaccine development, and a further expansion of evasion molecules as biomarkers, vaccines or targets for therapy appears likely in the future.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153126"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444716","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 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> &lt; 0.05) increases TCR mRNA expression, hematological indices, and lymphoid organ weights, while IL-10 declines (P &lt; 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> &gt; 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}

{"title":"NLRX1 as a novel therapeutic target: TRAF6-dependent inhibition of acute rejection in rat liver transplantation","authors":"Zilun Lei ,&nbsp;Tong Mou ,&nbsp;Hao Chai ,&nbsp;Qiang Liu ,&nbsp;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}

{"title":"The expression of OX40 in CD4+ T cells and its association with hepatic fibrosis injury","authors":"YaLing Xu ,&nbsp;WenNa Li ,&nbsp;Yuan Li ,&nbsp;Xin Li ,&nbsp;XinNa Li ,&nbsp;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}