Frontiers in Immunology最新文献

{"title":"Cerebrospinal fluid and serum cytokine profiles in severe viral encephalitis with implications for refractory status epilepticus: a retrospective observational study.","authors":"Peipei Huang, Fan Yang, Ruirui Dong, Lijun Wen, Qiuling Zang, Dandan Song, Junshuang Guo, Yating Wang, Ruike Zhang, Zhiping Ren, Jinjin Qin, Junfang Teng, Wang Miao","doi":"10.3389/fimmu.2025.1528763","DOIUrl":"10.3389/fimmu.2025.1528763","url":null,"abstract":"<p><strong>Background: </strong>To identify new intervention targets, we explored the correlation between cytokines and the development of refractory status epilepticus (RSE) in patients with severe viral encephalitis (SVE).</p><p><strong>Methods: </strong>We examined the characteristics of 14 cytokines in the cerebrospinal fluid (CSF) and serum, analyzing their correlation with acute symptomatic seizures and prognosis. Furthermore, we conducted a dynamic analysis of differences and correlations in the expression of cytokines among patients with SVE without seizures, those with controlled seizures, and those with RSE.</p><p><strong>Results: </strong>We included 161 patients with SVE; the incidence of seizures was 55.2%, and the mortality rate was 5.5%. Notably, 18.9% of these patients developed RSE, with a mortality rate of 20%. During the early stage of SVE, CSF interleukin (IL)-6 and IL-8 levels were significantly higher, declining over time and affecting the prognosis. CSF IL-6 and IL-8 levels were significantly elevated in the RSE group compared to patients without seizures and with controlled seizures, decreasing gradually and independently of serum cytokine levels. CSF IL-8 and age were independent risk factors for RSE, with clinical utility.</p><p><strong>Conclusions: </strong>Patients with SVE exhibit intrathecal cytokine storms, primarily characterized by elevated levels of IL-6 and IL-8, which influence prognosis. The strong and persistent hyperinflammation underscored by CSF IL-6 and IL-8 is associated with the occurrence and development of RSE; thus, CSF IL-8 and age are independent risk factors for SVE with RSE, indicating potential anti-inflammatory intervention targets.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1528763"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing transcriptomic biomarkers for TAVO412 utilizing next generation sequencing analyses of preclinical tumor models.","authors":"Ying Jin, Peng Chen, Huajun Zhou, Guangmao Mu, Simin Wu, Zhengxia Zha, Bin Ma, Chao Han, Mark L Chiu","doi":"10.3389/fimmu.2025.1505868","DOIUrl":"10.3389/fimmu.2025.1505868","url":null,"abstract":"<p><strong>Introduction: </strong>TAVO412, a multi-specific antibody targeting epidermal growth factor receptor (EGFR), mesenchymal epithelial transition factor (c-Met), and vascular endothelial growth factor A (VEGF-A), is undergoing clinical development for the treatment of solid tumors. TAVO412 has multiple mechanisms of action for tumor growth inhibition that include shutting down the EGFR, c-Met, and VEGF signaling pathways, having enhanced Fc effector functions, addressing drug resistance that can be mediated by the crosstalk amongst these three targets, as well as inhibiting angiogenesis. TAVO412 demonstrated strong <i>in vivo</i> tumor growth inhibition in 23 cell-line derived xenograft (CDX) models representing diverse cancer types, as well as in 9 patient-derived xenograft (PDX) lung tumor models.</p><p><strong>Methods: </strong>Using preclinical CDX data, we established transcriptomic biomarkers based on gene expression profiles that were correlated with anti-tumor response or distinguished between responders and non-responders. Together with specific driver mutation that associated with efficacy and the targets of TAVO412, a set of 21-gene biomarker was identified to predict the efficacy. A biomarker predictor was formulated based on the Linear Prediction Score (LPS) to estimate the probability of patients or tumor model response to TAVO412 treatment.</p><p><strong>Results: </strong>This efficacy predictor for TAVO412 demonstrated 78% accuracy in the CDX training models. The biomarker model was further validated in the PDX data set and resulted in comparable accuracy.</p><p><strong>Conclusions: </strong>In implementing precision medicine by leveraging preclinical model data, a predictive transcriptomic biomarker empowered by next-generation sequencing was identified that could optimize the selection of patients that may benefit most from TAVO412 treatment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1505868"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Immunity and pulmonary vascular diseases: challenges, advances and future perspectives.","authors":"Qi Jin, Daxin Zhou, Zhihong Liu, Djuro Kosanovic","doi":"10.3389/fimmu.2025.1563584","DOIUrl":"10.3389/fimmu.2025.1563584","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1563584"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of natural killer T and gammadelta T cells in mesothelin-targeted immunotherapy of pancreatic cancer.","authors":"Yuankui Zhu, Yaxi Yang, Linghe Yue, Lei Wan, Xuqian Ma, Qing Yang, Xuan Tian, Yuguan Li, Ke Wang, Shaozhong Wei, Dianbao Zuo, Mingqian Feng","doi":"10.3389/fimmu.2025.1524899","DOIUrl":"10.3389/fimmu.2025.1524899","url":null,"abstract":"<p><p>Current pancreatic cancer immunotherapy focused on alphabeta (αβ) T cells, either through CD3-engaged bispecific antibodies or CAR-T. Despite their promise, dose-limited toxicity (DLT) remains a challenge in clinical practice. In light of these concerns, there is a growing interest in exploring alternative T cell types, natural killer T (NKT) cells and gammadelta (γδ) T cells, that possess the capacity to lyse tumors while potentially offering a safer therapeutic profile with fewer side effects. These cells present a compelling alternative that warrants a comprehensive evaluation of their therapeutic potential and safety profile. This study employed a MSLN/CD3 bispecific antibody to compare the anti-tumor activity of NKT and γδT cells with peripheral blood mononuclear cells (PBMCs) as controls, both <i>in vitro</i> and <i>in vivo</i>. This study demonstrated that MSLN/CD3 BsAb effectively activated and recruited PBMCs, NKT and γδT. Furthermore, under the influence of MSLN/CD3 BsAb, γδT and NKT cells exhibited notably superior anti-tumor activity compared to PBMCs, both <i>in vitro</i> and <i>in vivo</i>, while demonstrating low cytokine release. γδT cells showed almost negligible toxic side effects. In addition, the systemic administration of NKT and γδT cells activators, α-galactosylceramide (α-GalCer) and Zoledronate, could enhance the anti-tumor effect of MSLN/CD3 bsAb, with no apparent toxicity. NKT and γδT cells are promising synergistic therapeutic cell types that may overcome the limitations of CD3 bispecific antibodies in pancreatic tumor treatments, offering a new perspective for clinical applications in immunotherapy.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1524899"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of the interleukin family in liver fibrosis.","authors":"Zixin Zhang, Jiahui Wang, Hui Li, Qun Niu, Yujing Tao, Xin Zhao, Zijian Zeng, Haijian Dong","doi":"10.3389/fimmu.2025.1497095","DOIUrl":"10.3389/fimmu.2025.1497095","url":null,"abstract":"<p><p>Liver fibrosis represents a wound-healing response to chronic liver injury caused by viral infections, alcohol, and chemicals agents. It is a critical step in the progression from chronic liver disease to cirrhosis and hepatocellular carcinoma. No chemical or biological drugs have been approved for the treatment of liver fibrosis. Relevant studies have demonstrated that effective inhibition of hepatitis B virus (HBV) replication by nucleoside (acid) analogs or polyethylene glycol alpha-interferon can lead to recovery in some patients with hepatitis B liver fibrosis, However, some patients with liver fibrosis do not show improvement, even after achieving a complete serologic and virologic response. A similar situation occurs in patients with hepatitis C-related liver fibrosis. The liver, with its unique anatomical and immunological structure, is the largest immune organ and produces a large number of cytokines in response to external stimuli, which are crucial for the progression of liver fibrosis. cytokines can act either by directly affecting hepatic stellate cells (HSCs) or by indirectly regulating immune target cells. Among these, the interleukin family activates a complex cascade of responses, including cytokines, chemokines, adhesion molecules, and lipid mediators, playing a key role in the initiation and regulation of inflammation, as well as innate and adaptive immunity. In this paper, we systematically summarize recent literature to elucidate the pathogenesis of interleukin-mediated liver fibrosis and explore potential therapeutic targets for liver fibrosis treatment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1497095"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of short-chain fatty acid in metabolic syndrome and its complications: focusing on immunity and inflammation.","authors":"Wenqian Yu, Siyuan Sun, Qiang Fu","doi":"10.3389/fimmu.2025.1519925","DOIUrl":"10.3389/fimmu.2025.1519925","url":null,"abstract":"<p><p>Metabolic syndrome (Mets) is an important contributor to morbidity and mortality in cardiovascular, liver, neurological, and reproductive diseases. Short-chain fatty acid (SCFA), an organismal energy donor, has recently been demonstrated in an increasing number of studies to be an important molecule in ameliorating immuno-inflammation, an important causative factor of Mets, and to improve lipid distribution, blood glucose, and body weight levels in animal models of Mets. This study reviews recent research advances on SCFA in Mets from an immune-inflammatory perspective, including complications dominated by chronic inflammation, as well as the fact that these findings also contribute to the understanding of the specific mechanisms by which gut flora metabolites contribute to metabolic processes in humans. This review proposes an emerging role for SCFA in the inflammatory Mets, followed by the identification of major ambiguities to further understand the anti-inflammatory potential of this substance in Mets. In addition, this study proposes novel strategies to modulate SCFA for the treatment of Mets that may help to mitigate the prognosis of Mets and its complications.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1519925"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GNA15 predicts poor outcomes as a novel biomarker related to M2 macrophage infiltration in ovarian cancer.","authors":"Qin Liu, Yabing Sun, Tao Zhang, Wanrun Lin, Jing Zhang, Huijuan Zhang, Wenxin Zheng, Hong Xu, Feng Zhou","doi":"10.3389/fimmu.2025.1512086","DOIUrl":"10.3389/fimmu.2025.1512086","url":null,"abstract":"<p><strong>Background: </strong>The exploration of genetic signatures within the ovarian cancer (OC) tumor microenvironment (TME) remains limited. M2-like tumor-associated macrophages (M2-like TAMs) are pivotal in OC progression and therapy. This study aims to establish a novel prognostic signature and identify M2-like TAM-related biomarkers in OC using RNAseq-based transcriptome analysis.</p><p><strong>Methods: </strong>Prognostic M2-like TAM-related genes were identified through univariate Cox regression, consensus clustering, and LASSO regression. Immune landscape analysis was conducted to assess immune cell composition and immune checkpoint genes in high- and low-risk groups. Subsequently, <i>in vitro</i> cell experiments and OC cohorts were performed.</p><p><strong>Results: </strong>Gene set enrichment analysis revealed that GNA15 is involved in immune responses like leukocyte transendothelial migration and FcγR-mediated phagocytosis. GNA15 was up-regulated in cisplatin-resistant OC cells, and its <i>in vitro</i> down-regulation decreased cell proliferation. An eight-gene prognostic model, including M2-like TAM-related genes, independently predicted poor outcomes in OC. GNA15 emerged as a hub gene positively correlated with M2-like TAMs infiltration, predicting unfavorable outcomes across OC cohorts. Moreover, GNA15 expression correlated positively with CD163 expression, suggesting its role in macrophage polarization.</p><p><strong>Conclusion: </strong>GNA15 plays an immunosuppressive role in OC progression linked to M2-like TAMs polarization and stands as a potential prognostic marker in OC.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1512086"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis reveals the sensitivity of immunotherapy for unresectable non-small cell lung cancer.","authors":"Rui Wu, Kunchen Wei, Xingshuai Huang, Yinge Zhou, Xiao Feng, Xin Dong, Hao Tang","doi":"10.3389/fimmu.2025.1479550","DOIUrl":"10.3389/fimmu.2025.1479550","url":null,"abstract":"<p><strong>Background: </strong>To construct a prediction model consisting of metabolites and proteins in peripheral blood plasma to predict whether patients with unresectable stage III and IV non-small cell lung cancer can benefit from immunotherapy before it is administered.</p><p><strong>Methods: </strong>Peripheral blood plasma was collected from unresectable stage III and IV non-small cell lung cancer patients who were negative for driver mutations before receiving immunotherapy. Then we classified samples according to the follow-up results after two courses of immunotherapy and non-targeted metabolomics and proteomics analyses were performed to select different metabolites and proteins. Finally, potential biomarkers were picked out by applying machine learning methods including random forest and stepwise regression and prediction models were constructed by logistic regression.</p><p><strong>Results: </strong>The presence of metabolites and proteins in peripheral blood plasma was causally associated with both non-small cell lung cancer and PD-L1/PD-1 expression levels. A total of 2 differential metabolites including 5-sulfooxymethylfurfural and Anthranilic acid and 2 differential proteins including Immunoglobulin heavy variable 1-45 and Microfibril-associated glycoprotein 4 were selected as reliable biomarkers. The area under the curve (AUC) of the prediction model built on clinical risks was merely 0.659. The AUC of metabolomics prediction model was 0.977 and the AUC of proteomics was 0.875 while the AUC of the integrative-omics prediction model was 0.955.</p><p><strong>Conclusions: </strong>Metabolic and protein biomarkers in peripheral blood both have high efficacy and reliability in the prediction of immunotherapy sensitivity in unresectable stage III and IV non-small cell lung cancer, but validation in larger population-based cohorts is still needed.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1479550"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOX4 modulates breast cancer progression through cancer cell metabolic reprogramming and CD8⁺ T cell antitumor activity.","authors":"Yingying Xiong, Yiming Weng, Shan Zhu, Jian Qin, Jia Feng, Xiaopeng Jing, Chao Luo, Wei Gong, Rui Sun, Min Peng","doi":"10.3389/fimmu.2025.1534936","DOIUrl":"10.3389/fimmu.2025.1534936","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer is the most frequently diagnosed malignancy and a leading cause of cancer-related mortality among women worldwide. Although NADPH oxidase 4 (NOX4) has been implicated in various oncogenic processes, its exact function in breast cancer progression, metabolic reprogramming, and immune modulation remains unclear.</p><p><strong>Methods: </strong>We used murine 4T1 and EO771 breast cancer models to generate NOX4 knockout (KO) cell lines via CRISPR/Cas9. <i>In vitro</i> assays (cell proliferation, colony formation, wound healing, and Seahorse metabolic analyses) and <i>in vivo</i> orthotopic tumor studies assessed the impact of NOX4 loss. Transcriptomic changes were identified through RNA sequencing and gene set enrichment analysis. We performed MYC knockdown in NOX4 KO cells to investigate its mechanistic role. Flow cytometry characterized tumor-infiltrating immune cells. Finally, NOX4-overexpressing cells were tested for survival benefit and response to dual-checkpoint immunotherapy (anti-PD-1/anti-CTLA-4).</p><p><strong>Results: </strong>NOX4 deletion accelerated tumor growth <i>in vivo</i> and enhanced proliferation, colony formation, and migratory capacity <i>in vitro</i>. Metabolic profiling showed that NOX4 KO cells had elevated glycolysis and fatty acid oxidation, along with increased mitochondrial mass. Transcriptomic and enrichment analyses revealed MYC pathway activation in NOX4 KO cells; suppressing MYC reversed these hyperproliferative and metabolic changes. Immunologically, NOX4 KO reduced CD8+ T cell infiltration and function, partially due to lowered CCL11/CCL5 levels, while PD-L1 expression was upregulated. In contrast, NOX4 overexpression improved survival in mice and synergized with checkpoint blockade, demonstrating a positive effect on anti-tumor immunity.</p><p><strong>Discussion: </strong>These findings show that NOX4 constrains breast cancer aggressiveness by limiting MYC-driven metabolic adaptations and supporting CD8+ T cell-mediated immunity. Loss of NOX4 promotes a more malignant phenotype and dampens T cell responses, whereas its overexpression prolongs survival and enhances checkpoint inhibitor efficacy. Therapeutically targeting the NOX4-MYC axis and leveraging NOX4's immunomodulatory capacity could offer promising strategies for breast cancer management.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1534936"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of natural exosomes from SHED-MSC in immunoregulation of M0/M1 polarized macrophage cells.","authors":"Ali Fallah, Abasalt Hosseinzadeh Colagar, Ayyoob Khosravi, Azadeh Mohammad-Hasani, Mohsen Saeidi","doi":"10.3389/fimmu.2025.1550280","DOIUrl":"10.3389/fimmu.2025.1550280","url":null,"abstract":"<p><strong>Introduction: </strong>Exosomes (EXOs) as a targeted cell-free therapy could offer a new therapeutic strategy for immune-mediated inflammatory diseases, due to their stability and ease of storage and handling. This study focused on exosomes derived from stem cells of human exfoliated deciduous teeth (SHED-MSC-EXOs) and their role in managing the balance of immunoregulatory macromolecules that play a role in the underlying immunoregulatory mechanisms in THP-1-derived M0/M1 macrophage cells.</p><p><strong>Methods: </strong>Flow cytometry confirmed the expression of CD14, CD68, CD80, and CD86 markers in these macrophages. Following morphological and survival assessments, culture supernatants from SHED-MSCs were used to isolate exosomes. Once the exosomes were verified, Calcein AM-labeled EXOs were introduced to the macrophage cells. The immunoregulatory macromolecules were assessed by analyzing surface markers, cytokine production, and pro- and antioxidant activity.</p><p><strong>Results: </strong>Macrophages treated with exosomes exhibited immunomodulatory effects akin to those treated with dexamethasone. The levels of anti-inflammatory and antioxidant markers, including CD206, Arg-1, IL-10, TGF-β, TAC, CAT, and SOD, which act as immunosuppressive macromolecules, were elevated. In contrast, there was a reduction in pro-inflammatory and pro-oxidant markers, including CD80, CD81, IL-6R, IL-12, TNF-α, MDA, and NO, which act as immunostimulatory macromolecules (P < 0.05).</p><p><strong>Discussion: </strong>The findings suggest that exosomes derived from SHED-MSC can skew M0/M1 macrophages to the M2 phenotype and inhibit M1 polarization. These nanovesicles, with their distinct physical properties and ability to penetrate target cells, may prove beneficial in conditions involving the depletion of M2 macrophages and M1 macrophage-induced diseases, potentially aiding in the reduction of inflammation and tissue injury.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1550280"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}