Molecular immunology最新文献

{"title":"Neuritin-specific antibody impedes the Treg-mediated suppression of anti-tumor immunity and enhances response to anti-PD1","authors":"Kaimin Zhang ,&nbsp;Taowen Zhao ,&nbsp;Fraooq Riaz ,&nbsp;Yikui Li ,&nbsp;Ping Wei ,&nbsp;Xiang Fang ,&nbsp;Zhiyi Zhou ,&nbsp;Wei Kou ,&nbsp;Fan Pan","doi":"10.1016/j.molimm.2025.03.013","DOIUrl":"10.1016/j.molimm.2025.03.013","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) and effector T cells play critical roles in tumor immunity, with Tregs suppressing immune responses and contributing to an immunosuppressive tumor microenvironment (TME). Neuritin-1 (Nrn), a neuropeptide, has been identified to enhance Treg expansion. However, its role in T cell biology and tumor development remains unclear. We demonstrated that Nrn is highly expressed in the in-vitro-induced Tregs (iTregs). Functionally, Nrn promoted iTreg differentiation in a dose-dependent manner, while Nrn deletion or anti-Nrn antibody treatment significantly inhibited iTreg differentiation. Additionally, Nrn suppressed IL-2 transcription and secretion in T cells, impairing T cell activation and pro-inflammatory cytokine production. Treg-specific Nrn knockout mice exhibited reduced B16 melanoma tumor growth, decreased Treg infiltration, and increased effector T cell infiltration. Conversely, overexpression of Nrn accelerated B16 melanoma tumor progression by enhancing Treg-mediated suppression. Importantly, we developed the first anti-Nrn antibody, which effectively reduced tumour growth, decreased Treg infiltration, and enhanced effector T-cell activity. Importantly, anti-Nrn synergistically worked with anti-PD1 and improved the anti-PD1 response by reducing Tregs and increasing effector function in tumor-infiltrated T cells, resulting in enhanced tumor regression. Our findings identify Nrn as a critical regulator of Treg differentiation and effector T cell suppression, contributing to tumor progression. Targeting Nrn alone or combined with anti-PD1 therapy represents a promising strategy to enhance anti-tumor immunity.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 148-159"},"PeriodicalIF":3.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compound C1 reduced inflammation and activated autophagy in alveolar macrophages in mice","authors":"Qi Sheng ,&nbsp;Jie Zhao ,&nbsp;Shujun Chen ,&nbsp;Jingmin Zeng ,&nbsp;Shaogui Wang ,&nbsp;Jinping Wang","doi":"10.1016/j.molimm.2025.03.010","DOIUrl":"10.1016/j.molimm.2025.03.010","url":null,"abstract":"<div><div>The purpose of this study was to investigate the therapeutic effect of Compound C1 (Comp-C1) on lipopolysaccharide (LPS) -mediated sepsis acute lung injury (SALI) in vitro alveolar macrophage model and its regulatory mechanism. In vitro cultured mouse alveolar macrophages (MH-S) were treated with LPS. The expression and localization of transcription factor EB (TFEB) after LPS stimulation were detected. Then the cells were treated with LPS (1 μg/mL) and Comp-C1 (1 μM) for 24 h. RT-qPCR and Western Blot were used to detect the mRNA expression of inflammatory factors. Western blot was used to detect the expression of TFEB, lysosome-associated membrane protein 1 (LAMP1), P62 and microtubule-associated protein 1 light chain 3B (LC3B). TFEB-EGFP-Hela and mCherry-EGFP-LC3-Hela cells were used to detect the changes of TFEB nuclear expression and intracellular autophagic flux after Comp-C1 administration by immunofluorescence. The results showed that the expression of inflammatory factors was the highest after 1 μg / mL LPS stimulation for 24 hours. At the same time, the expression of TFEB gene and protein decreased after LPS stimulation, and the content of TFEB in cytoplasm and nucleus decreased by separating cytoplasmic and nuclear proteins. The content of LAMP1 decreased, and the expression of autophagy-related proteins reflected the inhibition of autophagy. After treatment with Comp-C1, the inflammatory factors were significantly decreased, the expression of TFEB and LAMP1 was significantly increased, and the expression of autophagy genes in the cells was restored. The up-regulation of TFEB nuclear expression after Comp-C1 administration was determined by TFEB-EGFP-Hela cells, and the recovery of autophagy flux and alveolar macrophage function after Comp-C1 administration was determined by mCherry-EGFP-LC3-Hela cells. Therefore, Comp-C1 can alleviate LPS-induced MH-S autophagy dysfunction and reduce inflammatory response by up-regulating TFEB in mouse alveolar macrophages, suggesting that Comp-C1 can be used as a potential drug for the treatment of SALI</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 139-147"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Darutoside promotes skin wound healing via regulating macrophage polarization","authors":"Linpei Gao ,&nbsp;Jing Su ,&nbsp;Lijia Guo ,&nbsp;Sheng Lin ,&nbsp;Junji Xu ,&nbsp;Yi Liu","doi":"10.1016/j.molimm.2025.03.008","DOIUrl":"10.1016/j.molimm.2025.03.008","url":null,"abstract":"<div><div>Wound healing is a complex and dynamic process of tissue formation, while polarization of macrophages plays an important role during this process. Darutoside is one of the major components of the ethanol extract from Siegesbeckia, which has the effects of anti-inflammation, healing rheumatism and promoting joint health. To investigate whether darutoside could promote wound healing, we established full-thickness excisional cutaneous wound healing model in C57/BL6 mice and applied darutoside on the skin wounds. The results showed that darutoside can improve wound healing in mice. Mechanistically, we treated RAW264.7 and macrophages with darutoside <em>in vitro</em>, and found that darutoside inhibited the LPS-induced polarization and pro-inflammatory cytokines expression in macrophages by inhibiting NF-κB signaling pathway. For <em>in vivo</em> study, we also found that darutoside could promote the growth of epithelial cells in wound tissue and inhibit the expression of iNOS+ macrophages around wound tissue by IHC staining. In addition, we also found that darutoside could inhibit the expression of inflammatory factors in wound tissue by PCR. Our data revealed that darutoside could promote wound healing by regulating macrophage polarization via inhibition of NF-κB signaling pathway.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 129-138"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in dendritic cell-based therapeutic tumor vaccines","authors":"Simin Qin ,&nbsp;Jintong Na ,&nbsp;Qun Yang ,&nbsp;Jing Tang ,&nbsp;Yamin Deng ,&nbsp;Liping Zhong","doi":"10.1016/j.molimm.2025.03.005","DOIUrl":"10.1016/j.molimm.2025.03.005","url":null,"abstract":"<div><div>Dendritic cell-based therapeutic tumor vaccines are an active immunotherapy that has been commonly tried in the clinic,traditional treatment modalities for malignant tumors, such as surgery, radiotherapy and chemotherapy, have the disadvantages of high recurrence rates and side effects. The dendritic cell vaccination destroys cells from tumors by means of the patient's own system of immunity, a very promising treatment. However, due to the suppression of the tumor immune microenvironment, the difficulty of screening for optimal specific antigens, and the high technical difficulty of vaccine production. Most tumor vaccines currently available in the clinic have failed to produce significant clinical therapeutic effects. In this review, the fundamentals of therapeutic dendritic cells vaccine therapy are briefly outlined, with a focus on the progress of therapeutic Dendritic cells vaccine research in the clinic and the initiatives undertaken to enhance dendritic cell vaccinations' anti-tumor effectiveness. It is believed that through the continuous exploration of novel therapeutic strategies, therapeutic dendritic cells vaccines can play a greater role in improving tumor treatment for tumor patients.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 113-128"},"PeriodicalIF":3.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-33 facilitates endoplasmic reticulum stress and pyroptosis in LPS-stimulated ARDS model in vitro","authors":"Pei-long Li ,&nbsp;Hong-min Fu ,&nbsp;Kai Liu ,&nbsp;Hai-feng Liu ,&nbsp;Ming-ze Sui ,&nbsp;Jia-wu Yang","doi":"10.1016/j.molimm.2025.03.007","DOIUrl":"10.1016/j.molimm.2025.03.007","url":null,"abstract":"<div><h3>Background</h3><div>Inflammatory activation of pulmonary microvascular endothelial cells (PMVECs) initiated by endoplasmic reticulum stress (ERS) contributes to acute respiratory distress syndrome (ARDS). Interleukin 33 (IL-33) has pro-inflammatory and transcriptional regulatory effects. Therefore, this study intends to investigate the effect of IL-33 on ERS and pyroptosis in the hPMVEC.</div></div><div><h3>Methods</h3><div>The hPMVEC-associated ARDS cell model was induced with lipopolysaccharide (LPS) and treated with 4-PBA (ERS inhibitor), thapsigargin (ERS activator), or IL-33 neutralizing antibody. Western blot and IF staining were performed to analyze the expression of cell-cell junction-associated (Cx37, Cx40, Cx43, Occludin, and Zo-1), ERS-associated (ATF6, IRE1a, and p-Erk), and pyroptosis-associated (NLRP3, IL-1β, and IL-18) proteins. Bioinformatics identified differential expression of IL-33 in ARDS-related datasets and targets of thapsigargin.</div></div><div><h3>Results</h3><div>IL-33 was highly expressed in serum of ARDS patients and in ARDS cohorts from multiple GEO datasets (GSE237260, GSE216635, GSE89953, GSE263867, and GSE5883), and was significantly correlated with clinical features. 4-PBA decreased permeability and IL-33 levels, and increased Cx37, Cx40 and Cx43 levels in the ARDS cell model. IL-33 neutralizing antibody effectively augmented the levels of Cx43 and Zo-1, and diminished the levels of ATF6, IRE1a, p-Erk, NLRP3, IL-1β, IL-18, ROS, and Ca^2 +. The therapeutic effect of IL-33 neutralizing antibodies was reverted by thapsigargin. Moreover, the Swiss Target Prediction and Super-PRED databases obtained 140 and 122 thapsigargin targets, which had 14 intersections. These intersections were associated with immunity, inflammation, apoptosis, pyroptosis, and Ca²⁺ homeostasis. Notably, CASP8 and PTGS2 interacted with IL-33 in these intersections.</div></div><div><h3>Conclusion</h3><div>IL-33 promotes ERS and pyroptosis, thereby contributing to barrier damage in ARDS cell models. IL-33 is a promising therapeutic target for ARDS.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 102-112"},"PeriodicalIF":3.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the anti-inflammatory, anti-oxidant and anti-apoptotic activity of 18β- glycyrrhetinic-acid on the model of LPS-induced lung injury in rats","authors":"Selina Aksak Karamese ,&nbsp;Volkan Gelen ,&nbsp;Gulfem Nur Yildiz ,&nbsp;Kevser Albayrak ,&nbsp;Semin Gedikli ,&nbsp;Adem Kara ,&nbsp;Murat Karamese","doi":"10.1016/j.molimm.2025.03.009","DOIUrl":"10.1016/j.molimm.2025.03.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Our aim was to investigate the protective effects of 18β-Glycyrrhetinic-acid (50 and 100 mg/kg i.g) on LPS-induced rat sepsis model by analyzing some immune mechanisms including inflammation, apoptosis, and oxidative stress parameters by different techniques such as Mallory’s Trichome staining, ELISA, tissue biochemistry and Western Blotting.</div></div><div><h3>Methods</h3><div>Forty-eight Sprague Dawley rats divided into 6 groups as follows: (i) Control, (ii) DMSO, (iii) LPS induced-Sepsis, (iv) LPS induced-Sepsis+ 18β-GA 50 mg/kg, (v) LPS induced-Sepsis + 18β-GA 100 mg/kg, (vi) 18β-GA 100 mg/kg. The pro-inflammatory cytokine (IFNγ, IL-1ß, TNF- α) levels were measured by ELISA technique. All rat’s lung tissues micrographed with Mallory’s Trichome stain. Oxidative stress parameters (MDA, GSH, SOD, NRF2, and HO-1), TLR4 signaling, and apoptotic proteins (Bcl-2 and Caspase-3) were detected by using tissue biochemistry and Western blotting.</div></div><div><h3>Results</h3><div>LPS administration caused a significant increase in all pro-inflammatory cytokine and oxidant levels. Shedding of bronchiolar epithelium, thickening of alveolar septa and vascular dilatation in LPS groups’ lung tissue were revealed according to the histopathological findings. The H-scores of 18β-GA50 +LPS and 18β-GA100 +LPS groups were significantly lower than LPS groups’ (p &lt; 0.05). When lung tissue protein expression profiles were analyzed for HO-1, TLR4, IL-1β, TNF-α, Bcl-2, and Caspase-3 expression was higher in the LPS group than in the control. In addition, NRF2 and Bcl-2 protein expressions were higher in control, DMSO and 18β-GA100 groups, while it was the lowest level in LPS group.</div></div><div><h3>Conclusion</h3><div>18β-GA demonstrates significant protective effects against LPS-induced lung injury in rats by modulating various immune mechanisms. These findings indicate that 18β-GA, particularly at the higher dose, may be a potential therapeutic agent in managing sepsis by mitigating inflammation, oxidative stress, and apoptosis in lung tissue. The inflammation and oxidative stress parameters were decreased and the apoptotic markers were increased in treatment group. Further molecular studies should be performed to investigate the roles of some significant cellular signaling pathways.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 93-101"},"PeriodicalIF":3.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dock2 deficiency reveals abnormal activation and differentiation of T cells under the physiological condition","authors":"Li Xu ,&nbsp;Weijie Shen ,&nbsp;Jun Chen ,&nbsp;Huiru Lv ,&nbsp;Wenji He ,&nbsp;Tian-Sheng He ,&nbsp;Tianfu Guo ,&nbsp;Zhiping Liu","doi":"10.1016/j.molimm.2025.03.004","DOIUrl":"10.1016/j.molimm.2025.03.004","url":null,"abstract":"<div><div>Previous research has demonstrated that <em>Dock2</em> deficiency results in a reduction in both the quantity and proliferation rate of T cells, thereby heightening the host's vulnerability to various infections. Nevertheless, the impact of DOCK2 on T cell activation remains unexplored. In this study, we employed flow cytometry to assess the activation phenotype of T cells in the peripheral lymphoid tissues of wild-type (<em>Dock2</em>^<em>+/+</em>), DOCK2 heterozygous (<em>Dock2</em>^<em>+/-</em>) and DOCK2 knockout (<em>Dock2</em>^<em>-/-</em>) mice. Our findings revealed that, in comparison to <em>Dock2</em>^<em>+/+</em> mice, <em>Dock2</em>^<em>-/-</em> mice exhibited increased expression levels of CD44 and CD69 on CD4⁺ and/or CD8⁺ T cells within spleen and mesenteric lymph nodes (MLN). Additionally, there was a significant elevation in the proportions of IFN-γ⁺/CD4⁺, IFN-γ⁺/CD8⁺ and IL-4⁺/CD8⁺ T cells. Furthermore, the percentage of IL-17a⁺/CD4⁺ and IL-17a⁺/CD8⁺ T cells in the MLN of <em>Dock2</em>^<em>-/-</em> mice was higher than that observed in <em>Dock2</em>^<em>+/+</em> mice. These results suggest that <em>Dock2</em> deficiency induces aberrant T cell activation in peripheral lymphoid tissues. To further investigate the underlying mechanisms of this phenomenon, we conducted transcriptome sequencing on CD8⁺ T cells collected from all groups of mice. The results indicate that <em>Ccr2</em> and <em>Ifng</em> are potentially pivotal genes involved in the aberrant activation of T cells in <em>Dock2</em>^<em>-/-</em> mice. These findings contribute to elucidating the host defense mechanisms against foreign pathogens and advance our comprehension of the role of cytoskeleton-related proteins in the regulation of cellular immunity.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 75-83"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estradiol conjugation to estrogen receptorα upregulates Brms1 expression mediating M2 polarization of alveolar macrophages and exacerbating airway inflammation in asthmatic mice","authors":"Shu Dong ,&nbsp;Yingzi Chen ,&nbsp;Ya Li ,&nbsp;Xingyue Liu ,&nbsp;Jiaqi Yan ,&nbsp;Minyu Xie ,&nbsp;Fan Wu ,&nbsp;Minzhu Niu ,&nbsp;Feifei Shang ,&nbsp;Han Huang ,&nbsp;Wenwen Wu ,&nbsp;Shujun Guo ,&nbsp;Yulin Du ,&nbsp;Mengqing Hua ,&nbsp;Chuanwang Song","doi":"10.1016/j.molimm.2025.03.002","DOIUrl":"10.1016/j.molimm.2025.03.002","url":null,"abstract":"<div><div>Asthma is a common condition involving chronic airway inflammation that primarily affects women and boys. Estrogen levels correlate with the observed differences in the prevalence of asthma between the sexes, but the exact mechanism is unclear. This study established a castration mice (OVX) model through bilateral ovariectomy surgery, and subcutaneously injected estradiol (E2) into OVX asthmatic mice to analyze the effect of E2 on the onset of asthma. Then, airway inflammation was evaluated in the mice using airway resistance measurements, lung tissue hematoxylin and eosin staining, and eosinophil counts. Furthermore, the proportion of CD206-positive cells and the expression of M2 polarization markers, such as Arg1 and YM1, were detected in alveolar macrophages (AMs). The effects of different concentrations of E2 on M2 polarization of AMs were examined <em>in vitro</em>, and the types of estrogen receptors (ERs) involved were investigated. Transcriptome analysis combined with volcano plots and heatmaps were used to compare the differentially expressed genes to investigate the mechanism by which E2 affects M2 polarization of AMs. The results showed that female asthmatic mice had more severe airway inflammation and higher airway responsiveness than male asthmatic mice. E2 increased airway inflammation and airway resistance in asthmatic mice. E2 not only promoted M2 polarization of AMs in asthmatic mice <em>in vivo</em>, but also increased the expression of M2 markers, such as Arg1 and YM1, by AMs <em>in vitro</em>. The use of ERα antagonist AZD9496 reduced the effect of E2 on the promotion of M2 polarization in AMs. Analysis of transcriptome differences indicated that E2 upregulated expression of M2 breast cancer metastasis suppressor gene 1 (<em>Brms1</em>) in AMs. Notably, antagonism of ERα inhibited this upregulation of <em>Brms1</em> gene expression. Interference with <em>Brms1</em> mRNA production reduced the gene expression of <em>Arg1</em> and <em>YM1</em> in AMs undergoing M2 polarization after E2 stimulation. In summary, E2 exacerbates airway inflammation in asthmatic mice and binds to ERα, upregulating <em>Brms1</em> expression and mediating M2 polarization of AMs.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 84-92"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A retrospective study on the correlation between antibody levels and endothelial function in SLE patients: An analysis based on ultrasound and serum biomarkers","authors":"Huan Xia,&nbsp;Zaixing Pan,&nbsp;Yun Hong,&nbsp;Qingzhu Zhao,&nbsp;Weili Fan","doi":"10.1016/j.molimm.2025.02.018","DOIUrl":"10.1016/j.molimm.2025.02.018","url":null,"abstract":"<div><h3>Background</h3><div>Systemic lupus erythematosus (SLE) was a complex autoimmune disease characterized by a spectrum of clinical and immunological manifestations, with cardiovascular disease (CVD) being a leading cause of morbidity and mortality. Endothelial dysfunction was critical in the pathogenesis of atherosclerosis and other cardiovascular complications in SLE. This study aimed to investigate the correlation between autoantibody levels and endothelial function in SLE patients using ultrasound and serum biomarkers.</div></div><div><h3>Methods</h3><div>A retrospective case-control study was conducted with 317 SLE patients treated from December 2021 to December 2023. Patients were categorized based on Flow-Mediated Dilation (FMD) values into an abnormal endothelial function group (n = 191) and a normal function group (n = 126). Serum biomarkers, including soluble thrombomodulin (sTM), von Willebrand factor (vWF), and soluble vascular cell adhesion molecule-1 (sVCAM-1), were assessed. Autoantibody levels were measured using enzyme-linked immunosorbent assays for anti-double stranded DNA (anti-dsDNA), anti-Smith, and anticardiolipin antibodies levels. Statistical analyses, including correlation and logistic regression, were performed to determine associations between antibody levels and endothelial function.</div></div><div><h3>Results</h3><div>Higher levels of Anti-Smith were significantly associated with poorer endothelial function, while higher Anti-dsDNA levels were positive correlated with endothelial function (Anti-Smith: coefficient = −0.168, Std_Error = 0.027, t_value = −6.228, P &lt; 0.001; Anti-dsDNA: coefficient = 0.140, Std_Error = 0.022, t_value = 6.345, P &lt; 0.001). These results underscore the importance of antibody levels in assessing endothelial health.</div></div><div><h3>Conclusion</h3><div>This study highlights the intricate relationship between specific autoantibodies and endothelial dysfunction in SLE patients. Elevated sVCAM-1 and Anti-Smith levels were associated with a higher risk of endothelial impairment, whereas Anti-dsDNA antibodies showed a positively correlated better endothelial function.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 66-74"},"PeriodicalIF":3.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caveolin-1 protects against liver injury and lipid accumulation in alcoholic fatty liver via ferroptosis resistance","authors":"Weiju Xue ,&nbsp;Ning Guo ,&nbsp;Liang Shan ,&nbsp;Zhengsheng Zhang ,&nbsp;Yuquan Sun ,&nbsp;Yong Wang ,&nbsp;Xing Fang ,&nbsp;Xiuzhen Liu ,&nbsp;Jianjun Liu ,&nbsp;Chengmu Hu","doi":"10.1016/j.molimm.2025.02.012","DOIUrl":"10.1016/j.molimm.2025.02.012","url":null,"abstract":"<div><div>Alcoholic fatty liver (AFL) is one of the most common chronic liver diseases globally with complex and controversial pathogenesis. Recent evidence suggests that iron overload and lipid peroxidation are risk factors for AFL. Caveolin-1 (CAV1) is an important signal platform that can maintain lipid homeostasis during the development of non-alcoholic fatty liver. Here, we studied the effect of CAV1 on ferroptosis in AFL. The AFL mouse model was established by chronic-plus-binge alcohol feeding. In vitro, AML-12 cells were incubated with ethanol and oleic acid for 48 h. We found alcohol-induced AFL triggered ferroptosis and decreased CAV1 expression. Overexpression of CAV1 by CAV1 scaffolding domain peptides (CSD) attenuated liver injury and hepatic steatosis, as well as inhibited ferroptosis in AFL mice. Additionally, the effects of CAV1 on ferroptosis-related protein levels (such as SLC7A11, GPX4, and ACSL4) and lipid accumulation were reversed by its small interfering RNA administration. Ferroptosis agonist (Erastin) treatment abrogated CAV1 plasmid-mediated ferroptosis resistance and steatosis alleviation. Collectively, the results revealed a crucial role of CAV1 in preventing hepatic steatosis and ferroptosis in alcohol-induced liver injury, which may identify potential targets for the treatment of AFL.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 53-65"},"PeriodicalIF":3.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}