Cellular immunology最新文献

{"title":"Immunomodulatory effects of mesenchymal stromal cell secretome accelerate repair in a sickle cell disease wound model","authors":"Brysa M. Silveira ,&nbsp;Tiago O. Ribeiro ,&nbsp;Songeli M. Freire ,&nbsp;Beatriz Costa ,&nbsp;Vitor Valério Maffili ,&nbsp;Marilda Souza Gonçalves ,&nbsp;Mari Sogayar ,&nbsp;Roberto José Meyer Nascimento ,&nbsp;Vitor Fortuna","doi":"10.1016/j.cellimm.2025.105047","DOIUrl":"10.1016/j.cellimm.2025.105047","url":null,"abstract":"<div><div>Chronic leg ulcers (CLUs) are a debilitating complication of sickle cell disease (SCD), driven by persistent inflammation, immune dysregulation, and vascular dysfunction. Current therapies fail to correct the hostile immune microenvironment that impairs repair. Here, we investigated the therapeutic potential of the adipose-derived mesenchymal stromal cell (ASC) secretome as a cell-free immunomodulatory approach in a preclinical SCD wound model. Full-thickness excisional wounds were induced in Townes HbSS mice and treated topically with ASC secretome or vehicle control. Treatment accelerated wound closure, enhanced re-epithelialization, and reduced inflammatory infiltrates. Histology revealed advanced collagen deposition and matrix organization, while immunofluorescence demonstrated increased CD31, α-SMA, and SM22 expression, indicating neovascularization and perivascular maturation. Gene expression profiling showed early upregulation of IL-10, TGF-β, and ARG1 and later downregulation of TNF, IL-1β, and NOS2, reflecting a shift toward a reparative immune milieu. Increased F4/80⁺ macrophages together with elevated CD31⁺ vascular markers were consistent with immune–vascular interactions. Collectively, these findings demonstrate that ASC secretome restores immune balance, supports vascular integrity, and promotes tissue regeneration in SCD-associated chronic wounds. This study provides preclinical evidence for ASC secretome as a promising, scalable, and cell-free immunomodulatory therapy for refractory chronic wounds.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"418 ","pages":"Article 105047"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462955","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":"Exosomes from hypoxic pretreated BMSCs attenuate primary Sjögren's syndrome-induced skin injury via PPARγ-mediated M2-like macrophage activation","authors":"Xin Wang ,&nbsp;Xu Sun ,&nbsp;Xinmeng Yang ,&nbsp;Guixia Xu ,&nbsp;Yuan Wang ,&nbsp;Mingming Jin ,&nbsp;Chao Sun","doi":"10.1016/j.cellimm.2025.105023","DOIUrl":"10.1016/j.cellimm.2025.105023","url":null,"abstract":"<div><h3>Background</h3><div>Sjögren's syndrome (SS) is an autoimmune disorder identified by a triad of sicca symptoms, pain, and fatigue. SS-induced skin injury seriously affects people's health but remains unsolved. Accumulating investigations have confirmed that exosomes (Exos) originating from bone marrow mesenchymal stem cells (BMSCs) can bolster the stressed microenvironment and tissue repair. Present study aimed to unravel therapeutic effects regarding BMSC Exos on SS-induced skin injury.</div></div><div><h3>Methods</h3><div>In this study, an SS mouse model was constructed, and exosomes from BMSCs (Exos) and hypoxic pretreated BMSCs (HExos) were isolated. The therapeutic effects of exosomes in SS were identified using ELISA, immunohistochemistry, and immunofluorescence. High-throughput sequencing (HTS) was utilized to characterize differentially expressed genes between Exos and HExos.</div></div><div><h3>Results</h3><div>The data showed that Exos, especially HExo treatments, affected the inhibition of SS-induced inflammatory factor expression, cell apoptosis, ROS deposition, and collagen loss. HTS and RT-qPCR detection showed PPARγ functioned importantly for HExo-mediated protective effects against SS-induced skin injury. The in vitro experiment using RAW confirmed that PPARγ expression inhibited LPS-induced M1-like macrophage activation, which was confirmed using the PPARγ antagonist T0070907. PPARγ upregulation improved therapeutic effects regarding Exos upon skin injury in SS mice by promoting M2-like macrophage activation.</div></div><div><h3>Conclusion</h3><div>Taken together, our study found that exosomes from hypoxic pretreated BMSCs attenuated primary Sjögren's syndrome-induced skin injury via PPARγ delivery and promoted M2-like macrophage activation.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"418 ","pages":"Article 105023"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157462","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":"Follicular helper T cells and fibrotic diseases","authors":"Yixuan Ma ,&nbsp;Yue Zhou ,&nbsp;Miao Yu","doi":"10.1016/j.cellimm.2025.105024","DOIUrl":"10.1016/j.cellimm.2025.105024","url":null,"abstract":"<div><div>T follicular helper (Tfh) cells constitute a functionally specialized subset of CD4+ T lymphocytes that orchestrate germinal center (GC) responses, critically regulating B cell destination and the development of long-term humoral immunity. Emerging evidence implicates Tfh cells as key mediators in the pathogenesis of multiple fibrotic disorders across multiple organ systems, including systemic sclerosis (SSc), hepatic fibrosis, chronic kidney disease, idiopathic pulmonary fibrosis (IPF) and IgG4-Related Disease (IgG4-RD). This review synthesizes current understanding of Tfh cell biology in fibrosis, aiming to provide deeper insights into their involvement in pathogenesis and identify potential new therapeutic targets.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"418 ","pages":"Article 105024"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157017","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 inflammatory effects of a repeated exposure of human macrophages to PM2.5 from house dust-SRM 2585 are partially reversible and disrupt the LPS/CD14 signaling pathways","authors":"Lelong Marie ,&nbsp;Morin Laura ,&nbsp;Pottier Ivannah ,&nbsp;Andre Véronique ,&nbsp;Lecureur Valérie","doi":"10.1016/j.cellimm.2025.105048","DOIUrl":"10.1016/j.cellimm.2025.105048","url":null,"abstract":"<div><h3>Objectives</h3><div>To evaluate whether repeated exposures to house dust PM_2.5, used at nontoxic concentrations, activate human macrophages after one- and seven-days post-treatment, and whether such PM_2.5 exposure may alter their response to LPS.</div></div><div><h3>Methods</h3><div>Human monocyte-derived macrophages (MDMs) were repeatedly (4 consecutive days) exposed to 1 and 10 μg/cm² house dust PM_2.5 fraction of SRM 2585®. MDM phenotype and functions were evaluated by flow cytometry and ELISA one- and seven-days after the last PM_2.5 exposure with or without LPS priming during the last 24 h of exposure.</div></div><div><h3>Results</h3><div>PM_2.5 used at non cytotoxic concentrations induced a pro-inflammatory phenotype characterized by an increased expression of M1 macrophagic markers (CD40, CD80, CD86) and pro-inflammatory cytokines (IL-6, IL-8, TNFα) and a decreased expression of M2 macrophagic markers (CD163, CD204) and of the anti-inflammatory cytokine IL-10, however depending of post-exposure time and the concentration. PM_2.5-induced polarization profile of MDM was reversible when they were exposed to 1 μg/cm² but not to 10 μg/cm². PM_2.5-primed MDMs and then exposed to LPS showed a pro-inflammatory phenotype characterized by altered secretion of IL-8 and IL-10, a decreased expression of CD14, scavenger receptors (<em>SR</em>)-A1 and interferon responsive genes (CXCL9/10, ISG15) and a decrease of endocytosis and phagocytosis of bacteria.</div></div><div><h3>Conclusions</h3><div>Repeated exposures, even to low concentration of house dust PM_2.5, primed MDMs to a pro-inflammatory phenotype that is only partly reversible seven days post-exposure. The altered response of PM_2.5-pre-exposed MDMs to LPS might be due to, at least in part, impaired endocytosis crucial for the TLR4/CD14 pathway.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"418 ","pages":"Article 105048"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462956","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":"Differential heterologous immunological effects induced by ChAdOx1-S and BNT162b2 COVID-19 vaccines","authors":"Elisabeth A. Dulfer ,&nbsp;Büsra Geckin ,&nbsp;Martijn Zoodsma ,&nbsp;Leonie S. Helder ,&nbsp;Wenchao Li ,&nbsp;Reinout van Crevel ,&nbsp;Josephine S. van der Maat ,&nbsp;Yang Li ,&nbsp;Jorge Domínguez-Andrés ,&nbsp;Mihai G. Netea","doi":"10.1016/j.cellimm.2025.105038","DOIUrl":"10.1016/j.cellimm.2025.105038","url":null,"abstract":"<div><h3>Background</h3><div>The mRNA- and adenovirus-based COVID-19 vaccines may induce different heterologous effects on non-COVID morbidity. We aimed to investigate immunological mechanisms that may account for these differences.</div></div><div><h3>Methods</h3><div>We selected a subgroup of individuals from the TACTIC trial who had completed their COVID-19 vaccination scheme before the introduction of a BNT162b2 booster vaccine. Transcriptional activity, distribution of cell types and cytokine secretion were compared between those who were originally vaccinated with the adenovirus vaccine ChAdOx1-S, and those who had received the mRNA vaccine BNT162b2. Additionally, we investigated how these differences evolved after administration of a BNT162b2 booster vaccine.</div></div><div><h3>Results</h3><div>24 individuals were included in this study, with 15 volunteers (62.5%) having originally received an mRNA vaccine and 9 (37.5%) an adenovirus vector vaccine. We found that 84 gene sets were differentially expressed in PBMCs from the two vaccine groups following <em>ex-vivo</em> secondary stimulation. Although cell populations did not significantly differ, pro-inflammatory cytokine responses to most stimuli were consistently higher in the adenovirus group compared to the mRNA group. These differences decreased after an mRNA booster vaccine.</div></div><div><h3>Discussion</h3><div>Our study findings provide additional support to the hypothesis that mRNA- and adenovirus-based vaccines differ in their broad immunological effects. Specifically, our observation that adenovirus-based vaccination tends to result in higher pro-inflammatory cytokine responses might help explain the difference in the heterologous effects of the two types of vaccines. Knowledge about NSEs is increasingly important for making public health and policy decisions, particularly for vulnerable populations.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"418 ","pages":"Article 105038"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145387482","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":"Exploring novel strategies of oncolytic viruses and gut microbiota to enhance CAR-T cell therapy for colorectal cancer","authors":"Jia Yi ,&nbsp;Sangmu Quji ,&nbsp;Luxuan Guo ,&nbsp;Zhongqiu Chai ,&nbsp;Xianbin Kong ,&nbsp;Jingyan Meng","doi":"10.1016/j.cellimm.2025.105026","DOIUrl":"10.1016/j.cellimm.2025.105026","url":null,"abstract":"<div><div>Colorectal cancer (CRC), ranking as the third most prevalent malignant tumor globally (accounting for 10.0 % of new cancer cases) and the second leading cause of cancer-related deaths (9.4 % of cancer mortality), continues to escalate in incidence, posing a significant threat to human health. Although conventional therapies such as surgery, radiotherapy, and chemotherapy remain the clinical mainstay, their efficacy in improving patient survival and quality of life has reached a plateau, necessitating the exploration of novel therapeutic approaches. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a highly promising approach for cancer treatment. Notably, the complexity of the solid tumor microenvironment (TME) presents challenges for the application of CAR-T therapy in CRC, including antigen heterogeneity, immune suppression, and off-target toxicity. However, the development of multi-target CAR-T cells and their combination with immunomodulatory drugs holds significant clinical potential. Furthermore, in recent years, oncolytic virus (OV) therapy has garnered substantial attention due to its unique antitumor mechanisms. Our study demonstrates that OVs can precisely target CRC tissues, inducing tumor cell apoptosis through selective infection and intracellular replication while concurrently activating systemic antitumor immune responses and inhibiting angiogenesis, thereby achieving multidimensional therapeutic effects. Further investigations reveal that OVs can serve as gene delivery vectors for therapeutic molecules or synergize with chimeric antigen receptor T-cell (CAR-T) therapy and immune checkpoint inhibitors to significantly enhance treatment efficacy. Simultaneously, gut microbiota, a critical regulator of CRC progression, can influence both CAR-T and OVs therapies through metabolic modulation and immune remodeling. Building upon these mechanisms, this review innovatively proposes a tripartite “OVs-gut microbiota-CAR-T\" strategy: OVs may reprogram the immunosuppressive TME and release tumor antigens to enhance CAR-T infiltration and activity, while concurrent modulation of gut microbiota could further alleviate immunosuppression and reduce treatment toxicity, establishing a bidirectional synergistic loop. This interdisciplinary integration strategy may provide a groundbreaking approach to overcome current therapeutic limitations in CRC and advance precision tumor immunotherapy to new frontiers.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"417 ","pages":"Article 105026"},"PeriodicalIF":2.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091219","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 synergy of CD133 overexpression and TGF-β supplementation in tumorigenesis of ovarian cancer cell lines in a three-dimensional sphere forming model","authors":"Hao-Chien Hung ,&nbsp;Tsui-Lien Mao ,&nbsp;Ke-Hung Tsui ,&nbsp;Ming-Huei Fan ,&nbsp;Ainani Priza Minhalina ,&nbsp;Chao-Lien Liu","doi":"10.1016/j.cellimm.2025.105015","DOIUrl":"10.1016/j.cellimm.2025.105015","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer (OC) is a highly lethal gynecological malignancy, mainly due to chemoresistance and tumor recurrence. Cancer stem cells (CSCs) may be responsible for chemoresistance, and CSC has become a new target for treatment. In this study, we aimed to develop a three-dimensional (3D) OC model with well-recapitulated stemness in the tumor microenvironment (TME).</div></div><div><h3>Results</h3><div>We observed that the niche-like environment associated with CSC properties is characterized by the presence of CD133-positive cells during OC sphere induction. The cancer-associated fibroblast (CAF)-integrated 3D multicellular OC model recapitulates enhanced tumorigenicity and cytokine-mediated invasiveness more than the 2D monolayer culture. Chemoresistance of the 3D OC model is also acquired. In addition, the in vivo growth of an established xenograft model with a 3D CAF-integrated OC sphere exhibits proper stemness features and full cancer-associated markers for tumorigenesis.</div><div>After transduction of the CD133 gene into OC cells, gene ontology (GO) and KEGG pathway enrichment analyses reveal that cytokine-mediated endothelial mesenchymal transition (EMT) is possibly responsible for chemotherapy resistance and tumor progression, and enhanced PAR1, CXCR4, and PD-L1 expressions are also observed. In addition, we found that engineered chimeric antigen receptor (CAR)-T cells targeting PAR1 demonstrated significant in vitro cytotoxicity toward chemoresistant OC sphere with CD133 overexpression.</div></div><div><h3>Conclusions</h3><div>Taken together, our results show that a CD133-3D OC sphere recaptures TME that mimics a real late-stage OC condition, and it can act as a useful platform with mechanism-verifying in vitro and in vivo experiments in researching OC chemotherapy, immunotherapy, and cell therapy to discover new therapeutic approaches.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"417 ","pages":"Article 105015"},"PeriodicalIF":2.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919967","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":"Divergent metabolic rewiring shapes altered innate immunity","authors":"Mohua Liu,&nbsp;Xiao Wang,&nbsp;Xiaoya Qu,&nbsp;Yao Wang,&nbsp;Xihui Shen,&nbsp;Lei Xu","doi":"10.1016/j.cellimm.2025.105025","DOIUrl":"10.1016/j.cellimm.2025.105025","url":null,"abstract":"<div><div>Both trained immunity (TRIM) and endotoxin tolerance (ET) initiate similar metabolic reprogramming characterized by enhanced glycolysis following an initial stimulus. However, TRIM exhibited heightened immune activation upon restimulation, whereas ET showed suppressed innate immune response. This divergence is attributed to distinct metabolic intermediates accumulated after the initial stimulation. In TRIM, metabolites like fumarate and glutamine derivatives accumulate, reinforcing pro-inflammatory epigenetic modifications. Conversely, ET is characterized by increased itaconate and lactate levels, promoting anti-inflammatory epigenetic changes and metabolic paralysis. This review highlights metabolic intermediates as key regulators of innate immune fate decisions, presenting avenues for targeted immune modulation.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"417 ","pages":"Article 105025"},"PeriodicalIF":2.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019900","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":"Establishment of a multi-parameter flow cytometry method to identify and characterize neutrophil extracellular traps","authors":"Weixiang Liu ,&nbsp;Jieming Ping ,&nbsp;Ning Wu","doi":"10.1016/j.cellimm.2025.105014","DOIUrl":"10.1016/j.cellimm.2025.105014","url":null,"abstract":"<div><div>Neutrophil extracellular traps (NETs) are web-like decondensed DNA filaments released by activated neutrophils, decorated with antimicrobial proteins such as myeloperoxidase (MPO) and elastase. Although several methods exist to evaluate NETs formation, including fluorescent microscopy or scanning electron microscopy (SEM), and flow cytometry, each has inherent limitations that restrict widespread application. Given the increasing relevance of NETs in various pathophysiological contexts, we sought to develop a simple, specific, objective and cost-effective flow cytometry-based method to assess NETs both <em>in vitro</em> and <em>in vivo</em>. Our approach leverages multi-parametric flow cytometry to simultaneously evaluate cell size, granularity, DNA decondensation, histone citrullination, and intracellular MPO. This method enables reliable detection of NETs in purified neutrophils as well as in tissue samples. Its performance was validated in parallel with conventional microscopy, confirming specificity and reproducibility. Notably, this FACS-based method is faster, more economical, and free from observer-bias, making it especially well-suited for both research and clinical sample analysis.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"417 ","pages":"Article 105014"},"PeriodicalIF":2.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895389","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":"ANAPC5 mitigates acute lung injury through regulating macrophage M1/M2 polarization via the EGFR/CD24 axis","authors":"Yiqi Wang ,&nbsp;Xiuhua Zhang ,&nbsp;Jiannan Zhang ,&nbsp;Mingbo Zhao,&nbsp;Yang Chong,&nbsp;Quankuan Gu,&nbsp;Xianglin Meng,&nbsp;Mingyan Zhao","doi":"10.1016/j.cellimm.2025.105013","DOIUrl":"10.1016/j.cellimm.2025.105013","url":null,"abstract":"<div><div>Acute lung injury (ALI) is a respiratory disease induced by uncontrolled inflammatory responses in the lungs. The pathological features of ALI include alveolar structural damage and pulmonary edema, which ultimately leads to pulmonary dysfunction. ANAPC5 (Anaphase-promoting complex subunit 5) is an E3 ubiquitin ligase known for its anti-inflammatory properties. This study aims to investigate the effects of ANAPC5 on ALI and its underlying molecular mechanism. In the lung tissue of an ALI mouse model induced by lipopolysaccharide (LPS) administration, we observed downregulation of ANAPC5. Through both <em>in vivo</em> and <em>in vitro</em> experiments, we assessed the effect of ANAPC5 on lung injury by conducting pathological analysis and molecular biological detection. ANAPC5 overexpression alleviated inflammatory cell infiltration, reduced alveolar wall thickening, suppressed pulmonary inflammation, and decreased the levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung tissue of the ALI model. Moreover, ANAPC5 inhibited M1 polarization and promoted M2 polarization of macrophages both <em>in vitro</em> and <em>in vivo</em>. We also found that ANAPC5 significantly suppressed the activation and expression of the epidermal growth factor receptor (EGFR) through inducing its ubiquitination in macrophages. In LPS-induced M1 macrophages, the presence of EGFR significantly decreased CD24 expression, followed by reversing the inhibitory effects of ANAPC5 on inflammatory responses and macrophage polarization. Collectively, our findings suggest that ANAPC5 serves as a therapeutic molecular target that mitigates ALI through regulating macrophage M1/M2 polarization <em>via</em> the EGFR/CD24 axis.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"415 ","pages":"Article 105013"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865996","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}