International immunopharmacology最新文献

{"title":"Genetic evidence supporting causality between atopic dermatitis and chronic obstructive pulmonary disease","authors":"Yunyun Wang , Xiaoye Zhao , Ruixiang Wang , Yue Yang , Ruiyi Su , Jingwei Ni , Yihan Sun , Suyang Sun , Xiyu Zhou , Yu Yang , Yue Yu , Yuxi Shen , Shiqin Tang , Guanghui Xu , Xiaoyan Hou , Lina Xu , Jing Xiao , Tian Tian","doi":"10.1016/j.intimp.2025.114602","DOIUrl":"10.1016/j.intimp.2025.114602","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114602"},"PeriodicalIF":4.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-135a-5p/STAT6-mediated EMT regulates IL-4 secretion in non-small cell lung cancer to affect M2-like TAM polarization","authors":"Heng-Xing Gao ,&nbsp;Mei-Hui Liu ,&nbsp;Meng Fan ,&nbsp;Jie-Jun Zhou ,&nbsp;An-Qi Li ,&nbsp;Ming-Wei Chen","doi":"10.1016/j.intimp.2025.114623","DOIUrl":"10.1016/j.intimp.2025.114623","url":null,"abstract":"<div><div>Arginase 1 (Arg1), a key indicator of M2 polarization in tumor-associated macrophages (TAMs), plays a crucial role in inhibiting T-cell activation and proliferation by depleting local arginine levels, thereby facilitating tumor immune escape. The epithelial–mesenchymal transition (EMT), a fundamental biological process in cancer proliferation and progression, is intricately linked to the interactions between TAMs and cancer cells. However, the underlying mechanisms of EMT and how EMT-programmed cancer cells specifically modulate Arg1 expression in M2-like TAMs remain incompletely understood. Our comprehensive analysis confirmed that Arg1 expression was significantly upregulated in non-small cell lung cancer (NSCLC) tissues, and patients with elevated Arg1 levels exhibited a notably shorter overall survival. Furthermore, alterations in miR-135a-5p expression were found to profoundly influence the proliferation, migration, invasion, EMT, and apoptotic processes of NSCLC cells. Mechanistically, miR-135a-5p post-transcriptionally inhibited STAT6 expression by regulating its 3′-untranslated region (3’-UTR). Subsequently, the miR-135a-5p/STAT6 axis inhibited GATA3-mediated interleukin-4 (IL-4) secretion from NSCLC cells, ultimately suppressing Arg1 expression in M2-like TAMs. MiR-135a-5p may exert pivotal roles in modulating STAT6-induced EMT in tumor cells, which subsequently impacts IL-4-related Arg1 expression and M2 polarization of TAMs in NSCLC. This, in turn, reduced the capacity of M2-like TAMs to secrete tumor-promoting cytokines. Therefore, Arg1 holds potential as a diagnostic biomarker for NSCLC, and miR-135a-5p may emerge as a promising target for inhibiting NSCLC progression.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114623"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRx0237 induces apoptosis and enhances anti-PD-1 immunotherapeutic efficacy in anaplastic thyroid Cancer","authors":"Qingyang Ning ,&nbsp;Jiaye Liu ,&nbsp;Shijing Liu ,&nbsp;Quanqing Zou ,&nbsp;Kewei Li ,&nbsp;Zhihui Li","doi":"10.1016/j.intimp.2025.114610","DOIUrl":"10.1016/j.intimp.2025.114610","url":null,"abstract":"<div><div>Anaplastic thyroid cancer (ATC) is a highly malignant and lethal tumor with poor prognosis, but there is a lack of effective treatment strategies. In our study, we screened a drug library and identified that TRx0237, a tau protein inhibitor, showed inhibitory effect on ATC cells. Further research demonstrated that the inhibitory effect of TRx0237 was mainly through the induction of apoptosis via reactive oxygen species (ROS)-mediated endoplasmic reticulum stress pathway. Meanwhile, the pro-apoptosis effect and mechanism of TRx0237 on ATC were verified in xenograft and ATC patient-derived organoids. In addition, TRx0237 significantly upregulated the expression of PD-L1 in ATC, and synergistically enhanced the effect of anti-PD-1 therapy in xenograft and organoids model. Therefore, our study suggests that TRx0237 showed anticancer effects by inducing apoptosis and improving the efficacy of anti-PD-1 immunotherapy. TRx0237 is a potential agent for the treatment of ATC.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114610"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Pyroptosis in inflammatory bowel disease","authors":"Zhiyi Xiao ,&nbsp;Jiling Xie ,&nbsp;Xun Zhao ,&nbsp;Xiangjun Chen ,&nbsp;Yihong Lu ,&nbsp;Yuanzhao Xu ,&nbsp;Manqing Wu ,&nbsp;Lingyue An ,&nbsp;Qing Li","doi":"10.1016/j.intimp.2025.114619","DOIUrl":"10.1016/j.intimp.2025.114619","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) is a serious chronic condition marked by persistent and recurrent intestinal ulcers. Although the exact cause of IBD remains unclear, it is generally accepted that a complex interaction among dietary factors, gut microbiota, and immune responses in genetically predisposed individuals contributes to its development. Pyroptosis, an inflammatory form of programmed cell death activated by inflammasomes, is marked by the rupture of cell membranes and the subsequent release of inflammatory mediators. Emerging evidence indicates that pyroptosis plays a crucial role in the pathogenesis of IBD. Moderate pyroptosis activation can enhance intestinal immune defenses, while excessive inflammasome activation can trigger an inflammatory cascade, resulting in increased damage to intestinal tissues. This article reviews the molecular mechanisms underlying pyroptosis and highlights its role in the onset and progression of IBD. Furthermore, We explore recent advancements in IBD treatment, focusing on small molecule compounds that specifically target and inhibit pyroptosis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114619"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NUDT1 aggravates intestinal epithelial barrier injury through oxidative stress in ulcerative colitis","authors":"Guiyuan Jin ,&nbsp;Xizhuang Gao ,&nbsp;Fengxian Dai ,&nbsp;Hairong Zhang ,&nbsp;Tingting Lu ,&nbsp;Dehuai Jing ,&nbsp;Yonghong Yang ,&nbsp;Fengqin Zhu ,&nbsp;Guangxi Zhou","doi":"10.1016/j.intimp.2025.114634","DOIUrl":"10.1016/j.intimp.2025.114634","url":null,"abstract":"<div><h3>Background</h3><div>Nudix hydrolase 1 (NUDT1) plays a crucial role in tumours, where it helps limit cellular damage caused by reactive oxygen species. However, the exact function of NUDT1 in ulcerative colitis (UC) is not well understood.</div></div><div><h3>Methods</h3><div>NUDT1 expression in the intestinal mucosal tissues of patients with UC was analysed using quantitative reverse transcription polymerase chain reaction. A public database was used to analyse the expression of selected signature genes of interest in patients with UC with different NUDT1 expression levels. TH588, a potent NUDT1 inhibitor, was used to treat intestinal epithelial cells (IECs) in mice. The functions of the IECs were assessed using quantitative reverse transcription polymerase chain reaction, flow cytometry, western blotting, and fluorescence microscopy. A mouse model of dextran sodium sulphate-induced colitis was established.</div></div><div><h3>Results</h3><div>We examined NUDT1 expression and found that it was significantly elevated in the colon tissues of patients with UC. A colitis model was established in wild-type mice treated with TH588, which significantly reduced intestinal mucosal inflammation and induced notable alterations in faecal microbiota composition. Moreover, TH588 helped preserve intestinal mucosal barrier function. Inhibition of NUDT1 expression in IECs enhanced antioxidant activity by increasing Nrf2 expression and reducing ERK phosphorylation, which, in turn, stabilised tight junctions in IECs exposed to oxidative stress.</div></div><div><h3>Conclusions</h3><div>Our research emphasises the role of NUDT1 in modulating the intestinal microbiota and intestinal mucosal barrier in UC, indicating that targeting NUDT1 during intestinal mucosal inflammation could serve as a promising therapeutic strategy for UC.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114634"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploiting regulatory T cells (Tregs): Cutting-edge therapy for autoimmune diseases","authors":"Marwa Hassan ,&nbsp;Mohamed Elzallat ,&nbsp;Dina Mostafa Mohammed ,&nbsp;Mahmoud Balata ,&nbsp;Walaa H. El-Maadawy","doi":"10.1016/j.intimp.2025.114624","DOIUrl":"10.1016/j.intimp.2025.114624","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) are a specialized subset of suppressive T cells that are essential for maintaining self-tolerance, regulating effector T cells, managing microbial infections, preventing tumors, allergies, and autoimmune disorders, and facilitating allograft transplantation. Disruptions in Treg function or abundance contribute to an imbalance between pathogenic and protective immune cells in autoimmune diseases. Recently, one promising treatment strategy to restore immune balance involves the selective expansion or manipulation of Tregs using low-dose IL-2 therapy, adoptive Treg cell transfer, and chimeric antigen receptor (CAR)-Treg approaches. Tregs have been shown in an increasing number of research studies to prevent or even treat a variety of disorders, such as tumors, autoimmune and allergic diseases, transplant rejection, and graft-<em>versus</em>-host disease. A thorough comprehension of Treg function is anticipated to provide clear prospects for effective Treg immunotherapy in the treatment of a wide range of diseases. This review provides an overview of Tregs biology, including their functions, suppressive mechanisms, phenotypic markers, as well as their involvement in disease settings. Furthermore, we discuss the therapeutic potential of different Treg subpopulations and their translational applications in the treatment of autoimmune diseases.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114624"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NCOA3 impairs the efficacy of anti-PD-L1 therapy via HSP90α/EZH2/CXCL9 axis in colon cancer","authors":"Jiaqi Liu ,&nbsp;Yixi Su ,&nbsp;Chi Zhang ,&nbsp;Haiyan Dong ,&nbsp;Runfeng Yu ,&nbsp;Xin Yang ,&nbsp;Yu Tian ,&nbsp;Yanchun Feng ,&nbsp;Jingdan Zhang ,&nbsp;Mengchen Shi ,&nbsp;Chen Wang ,&nbsp;Weiqian Li ,&nbsp;Jun Liu ,&nbsp;Lingyuan He ,&nbsp;Xiangling Yang ,&nbsp;Huanliang Liu","doi":"10.1016/j.intimp.2025.114579","DOIUrl":"10.1016/j.intimp.2025.114579","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have revolutionized colon cancer treatment, but their efficacy is largely restricted by the limited presence of CD8⁺ cytotoxic T lymphocytes (CTLs). However, the specific genetic alterations that impact the CD8⁺ CTL infiltration in colon cancer remain poorly understood. Here, we analyzed clinical and multi-omics data from the Memorial Sloan-Kettering Cancer Center (MSKCC) ICIs-treated and The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) cohorts to screen the key mutations that may influence the efficacy of immunotherapy. We found that patients with NCOA3 mutations exhibit better response to immunotherapy and higher CD8⁺ CTL infiltration. In vitro and in vivo experiments revealed that mutant NCOA3 increases the efficacy of anti-PD-L1 and CD8⁺ CTL recruitment by upregulating C-X-C motif chemokine ligand 9 (CXCL9), which is dependent on its impaired intrinsic histone acetyltransferase activity. Mechanistically, wild-type NCOA3 as histone acetyltransferase upregulates Heat shock protein 90 alpha (HSP90α) by enhancing histone H3 lysine 27 acetylation (H3K27ac) at its promoter region. Increased HSP90α stabilizes Enhancer of zeste homolog 2 (EZH2), which then increase the histone H3 lysine 27 trimethylation (H3K27me3) at the CXCL9 promoter region, thereby suppressing the expression of CXCL9. Targeted inhibition of NCOA3 by small molecular inhibitor SI-2 improves the efficacy of PD-L1 blockade therapy. NCOA3 could serve as a novel biomarker and potential target to improve the efficacy of immunotherapy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114579"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ClC-3-depedent polarization of microglia protects against cerebral ischemic injury in mice","authors":"Meng-qing Wang ,&nbsp;Bin Wang ,&nbsp;Xu Yang ,&nbsp;Qi-chun Zhang ,&nbsp;Xu-yang Wang ,&nbsp;Yin-feng Dong","doi":"10.1016/j.intimp.2025.114618","DOIUrl":"10.1016/j.intimp.2025.114618","url":null,"abstract":"<div><div>Polarization of microglia has attracted great attention in ischemic stroke. Emerging evidence suggests that chloride channel 3 (ClC-3) is involved in inflammatory responses and stroke. However, the link between ClC-3 and polarization of microglia in ischemic stroke remains unclear. Herein, we found both cerebral ischemia and oxygen-glucose deprivation (OGD) induced a significant upregulation of ClC-3 in microglia. While knockdown of ClC-3 markedly increased nuclear factor kappa B (NF-κB) and CD86, and decreased CD206 in BV-2 cells under OGD conditions, facilitating them to shift into a M1-like phenotype. Furthermore, ClC-3 knockout significantly aggravated infarct volume and neurological deficits, accompanied by increased activated microglia in the peri-infarct area 1 day after cerebral ischemia. By contrast, ClC-3 overexpression obviously suppressed nuclear translocation of NF-κB, decreased OGD-induced elevated mRNA levels of TNF-α, IL-1β and IL-10, and enhanced M2-like markers (Arg1, CD206, and TREM2) in microglia, leading to alleviated infarct volume and neurological deficits. While ClC-3 overexpression could not reverse a transformation from M1-like phenotype to M2-like polarization in presence of lipopolysaccharide (LPS) and interferon gamma (IFNγ) treatment for 24 h. Collectively, our findings indicate that ClC-3-dependent polarization of microglia is critically important for protecting against cerebral ischemia injury, suggesting ClC-3 is a promising therapeutic target for ischemic stroke.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114618"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marine-derived STING inhibitors, excavatolide B promote wound repair in full-thickness-incision rats","authors":"Chun-Kai Chang ,&nbsp;Zong-Sheng Wu ,&nbsp;Guang-Hao Niu ,&nbsp;Yu-Yu Chou ,&nbsp;Shih-Hsuan Tang ,&nbsp;Mingzi M. Zhang ,&nbsp;Chun-Sung Sung ,&nbsp;Hsiang-Ting Tung ,&nbsp;Lun Kelvin Tsou ,&nbsp;Chi-Chieh Tang ,&nbsp;Ping-Jyun Sung ,&nbsp;Yi-Hao Lo ,&nbsp;Zhi-Hong Wen","doi":"10.1016/j.intimp.2025.114593","DOIUrl":"10.1016/j.intimp.2025.114593","url":null,"abstract":"<div><div>The process of wound healing encompasses both inflammatory and proliferative stages. Excessive inflammation is known to impede the healing of chronic wounds. Activation of the cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway causes inflammation during cellular stress and tissue damage. Herein, we examined the anti-inflammatory effects of the marine-derived STING antagonist excavatolide B (EXCB) and its derivatives, EXCB-61 and EXCB-79, in full-thickness-incision rats. Wound area measurements, histopathological observations, and immunohistochemical analyses were performed to evaluate the roles of these compounds in wound healing. These three compounds were found to have low toxicity, with EXCB promoting Hs68 human dermal fibroblast migration and proliferation. EXCB and EXCB61 treatments, but not EXCB79, reduced the wound area. The histopathological results showed a significant decrease in immune cell infiltration and mast cell accumulation in all compound-treated groups. Immunohistochemical analysis revealed that EXCB and its derivatives reduced cGAS-STING pathway factors such as STING, phosphorylated TANK-binding kinase 1, nuclear factor kappa-light-chain-enhancer of activated B cells, and M1 macrophages while increasing the expression of angiogenic factors vascular endothelial growth factor and CD31, as well as M2 macrophages and collagen I/III deposition. We conclude that marine-derived STING antagonists can attenuate inflammatory responses by inhibiting the cGAS-STING pathway and promoting angiogenesis, thereby aiding wound healing.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114593"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-27 accelerates diabetic wound healing by modulating macrophage polarization","authors":"Li Tao ,&nbsp;Shu Wu ,&nbsp;Qian Wang ,&nbsp;Zhiliang Xi ,&nbsp;Ying Zou ,&nbsp;Mibu Cao ,&nbsp;Kaixin Liang ,&nbsp;Waner Xu ,&nbsp;Qian Hu ,&nbsp;Yuanlong Ge ,&nbsp;Zhinan Yin ,&nbsp;Zhenyu Ju ,&nbsp;Zhong Liu","doi":"10.1016/j.intimp.2025.114575","DOIUrl":"10.1016/j.intimp.2025.114575","url":null,"abstract":"<div><div>Diabetic foot ulcer (DFU), a serious complication of diabetes, is a life-threatening disease that often leads to lower limb amputation and a shortened lifespan. Interleukin-27 (IL-27) is a member of the IL-12 family and has the potential to exert dual effects on the immune response. The role of IL-27 in diabetic skin wound healing is unknown. The aim of this study was to investigate whether there is abnormal expression of IL-27 in diabetic skin and whether supplementation with IL-27 can promote diabetic wound healing by modulating macrophage polarization. We established a streptozotocin (STZ)-induced diabetic mouse model and constructed diabetic wounds. We assessed protein expression by western blotting (WB) and immunohistochemical (IHC) staining. We also performed hematoxylin–eosin (H&amp;E) staining and Masson's trichrome staining. In the presence of lipopolysaccharide (LPS) and high glucose (HG), we treated the mononuclear macrophage line RAW264.7 and bone marrow-derived macrophages (BMDMs) with IL-27. To assess macrophage polarization, we examined the expression of inducible nitric oxide synthase (iNOS), IL-1β and arginase-1 (Arg-1). To understand the underlying mechanisms, we used macrophage IL-27ra knockout mice to knockout macrophage IL-27 receptors. Our in vivo experiments revealed that the expression of IL-27 in the skin of diabetic mice was significantly decreased and that supplementation with IL-27 promoted diabetic wound healing. In vitro, compared with the LPS group, supplementation with IL-27 alleviated the suppression of multiple cellular functions, such as iNOS and IL-1β expression, cell migration, and phagocytosis, in macrophages after HG exposure. Mechanistically, we found that IL-27 expression was decreased and that the activation of signal transducer and activator of transcription 3 (STAT3) by phosphorylation was inhibited in diabetic skin, leading to an inability of wound macrophages to polarize to an M1 phenotype effectively, which in turn blocked M1-to-M2 polarization of wound macrophages and ultimately delayed wound healing. The present study revealed that supplementation with IL-27 promoted M1-to-M2 polarization of wound macrophages and diabetic wound healing through the IL-27–IL-27Rα–p-STAT3 axis. These findings suggest that IL-27 may be a potential therapeutic target for DFU.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114575"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}