Molecular immunology最新文献

{"title":"FNDC4 modulates macrophage responses and suppresses NF-κB in sepsis-induced lung injury","authors":"Jiameng Chen ,&nbsp;Juan Li ,&nbsp;Yingying Huang ,&nbsp;Yiwen Fan ,&nbsp;Wenjie Li ,&nbsp;Jiawei Ye ,&nbsp;Guoxiang Liu ,&nbsp;Bojie Jiang ,&nbsp;Shuming Pan ,&nbsp;Chengjin Gao","doi":"10.1016/j.molimm.2026.03.001","DOIUrl":"10.1016/j.molimm.2026.03.001","url":null,"abstract":"<div><div>Regulation of pulmonary macrophages and their related functions is crucial for preventing further deterioration in many diseases. Fibronectin III domain-containing 4 (FNDC4) is a secreted factor with high homology to the exercise-related myokine irisin (FNDC5) and has been reported to be significantly upregulated in multiple mouse models of inflammation and under human inflammatory conditions. Here, we investigated the role and mechanisms of FNDC4 in regulating pulmonary macrophage function and the NF-κB pathway in sepsis. Plasma samples and clinical data from sepsis patients and healthy volunteers were collected to quantify FNDC4 levels and analyze their association with sepsis severity. In vivo, septic rat models with different disease severities were established to evaluate the effects of FNDC4 on lung injury. In vitro, LPS-stimulated mouse macrophages (RAW264.7) were preincubated with varying concentrations of FNDC4 to explore its functional effects and underlying mechanisms. Clinically, plasma FNDC4 levels were lower in sepsis patients than in healthy controls and were positively correlated with sepsis severity. In animal experiments, FNDC4 administration effectively alleviated sepsis-induced lung injury. In cell-based assays, FNDC4 preserved the proliferation and migration of LPS-stimulated RAW264.7 cells and reduced their apoptosis rate, while also inhibiting phosphorylation-dependent activation within the NF-κB pathway. Collectively, these findings suggest that FNDC4 may reflect sepsis severity and that exogenous FNDC4 can mitigate sepsis-related lung damage in vivo, potentially through modulation of the NF-κB signaling pathway, indicating its potential therapeutic value in sepsis.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"193 ","pages":"Pages 68-78"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388202","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":"vtRNA1-1/p62 regulates macrophages autophagy in ankylosing spondylitis","authors":"Minxin Jiang ,&nbsp;Jianping Ni ,&nbsp;Xueying Yu ,&nbsp;Hui Zhao ,&nbsp;Xiaofeng Lu ,&nbsp;Lerong Cheng ,&nbsp;Ziqi Li ,&nbsp;Hanqing Wu ,&nbsp;Zelong Pan ,&nbsp;Lianchi Qu ,&nbsp;Mengyao Gao ,&nbsp;Guoqi Cai ,&nbsp;Mengmeng Wang ,&nbsp;Faming Pan","doi":"10.1016/j.molimm.2026.02.014","DOIUrl":"10.1016/j.molimm.2026.02.014","url":null,"abstract":"<div><div>This research aims to investigate the role and mechanisms of the vtRNA1–1/p62 molecular axis in the regulation of autophagy in AS, with the goal of identifying novel diagnostic and therapeutic targets for AS. Clinical sample analysis revealed that the transcription levels of vtRNA1–1 and p62 decreased in the peripheral blood mononuclear cells (PBMCs) of the AS group; conversely, the levels of canonical autophagy-related genes (ATG3, ATG5) and inflammatory factors (TNF-α) significantly increased. Correlation analysis revealed that vtRNA1–1 levels were positively associated with p62 but were inversely associated with ATG3, ATG5, and TNF-α. In vitro cell experiments demonstrated that vtRNA1–1 depletion reduced p62 expression while increasing ATG3, ATG5, and LC3B levels. Computational modeling further confirmed significant interactions between vtRNA1–1 and p62. Notably, vtRNA1–1 and p62 demonstrated unique diagnostic value for AS, with their combination showing even greater diagnostic significance. This study innovatively links noncoding RNA regulatory networks with autophagy homeostasis imbalance, revealing that vtRNA1–1 may regulate macrophage autophagy through p62, thereby participating in the molecular pathogenesis of AS.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"193 ","pages":"Pages 1-9"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372964","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":"Mechanistic study of swertiamarin in treating ulcerative colitis by regulating YAP-mediated Wnt and Notch pathways for intestinal stem cell repair","authors":"Jiawen Chen ,&nbsp;Hui Peng ,&nbsp;Jun Chen ,&nbsp;Yi Liu ,&nbsp;Lei Chen","doi":"10.1016/j.molimm.2026.02.012","DOIUrl":"10.1016/j.molimm.2026.02.012","url":null,"abstract":"<div><h3>Background</h3><div>Ulcerative colitis (UC) is a chronic immune-mediated inflammatory disease. In 2024, the American Gastroenterological Association updated its guidelines for UC patients, shifting the treatment goal from \"clinical remission\" to \"mucosal healing\" and \"histological healing.\" This highlights the vital role of the interaction between intestinal stem cells (ISCs) and immune cells in maintaining and repairing intestinal tissue homeostasis. However, effective regulatory approaches targeting ISC-immune crosstalk are lacking in current clinical practice. The traditional Chinese medicine Qinjiao, which is widely used in clinical prescriptions for treating UC, contains many iridoid compounds, but whether they can promote tissue healing by regulating the ISC immune microenvironment remains to be clarified.</div></div><div><h3>Methods</h3><div>UHPLC-MS and an ISC injury organoid model were applied to identify and screen the four major iridoid compounds in Qinjiao. Then, the pharmacodynamic effects of swertiamarin (SW) on UC mice, the proliferation and differentiation of colonic ISCs, and the related status of Wnt, Notch, and Hippo-YAP signaling pathways were analyzed using RT-qPCR and other methods. Finally, the mechanism in organoids was verified using the YAP inhibitor Verteporfin.</div></div><div><h3>Results</h3><div>This study found that SW, a bioactive iridoid compound from Qinjiao, alleviated weight loss, mitigated colon atrophy, and reduced DAI scores in UC mice. SW also restored the proliferation and differentiation of ISCs. It mitigated immune-inflammatory responses and repaired the mucosal barrier by modulating YAP nuclear translocation to activate Wnt/β-catenin signaling and downregulate Notch signaling, enhancing ISC proliferation and differentiation.</div></div><div><h3>Conclusion</h3><div>This study revealed that iridoid compounds, represented by SW, are the primary active components in Qinjiao for treating UC by restoring mucosal barrier integrity through enhanced ISC proliferation and differentiation.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"193 ","pages":"Pages 26-38"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388199","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":"Emerging molecular mechanisms of cGAS-STING activation and regulation","authors":"Yilin Liu ,&nbsp;Kanglong Ma ,&nbsp;Zhengfan Jiang","doi":"10.1016/j.molimm.2026.02.008","DOIUrl":"10.1016/j.molimm.2026.02.008","url":null,"abstract":"<div><div>The cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway is a crucial component of the innate immune system, responsible for detecting cytosolic double-stranded DNA (dsDNA) from both pathogen invasion and host damage, thereby initiating a robust type I-interferons (IFNs) response. In this review, we summarize the complex and stringent mechanisms governing the activation and regulation of the cGAS–STING pathway. We describe the structural basis of cGAS activation by dsDNA and its catalytic synthesis of 2’3’-cGAMP, and highlight the DNA-independent activation of cGAS by manganese (Mn^2 +), which exhibits a distinct catalytic mechanism. We also discuss recent advances in the regulatory mechanisms of cGAS. The binding of 2’3’-cGAMP triggers STING translocation from the ER to the Golgi apparatus, where sulfated glycosaminoglycans (sGAGs) act as an essential second ligand to promote STING polymerization. Following this, a second translocation from the trans-Golgi network (TGN) to endosomes is required for its full activation. Conversely, supranormal concentrations of 2′3'-cGAMP induce the formation of ER-localized STING biocondensates, which restrict activation and thus prevent an excessive immune response. Dysregulation of the cGAS–STING pathway has been implicated in diverse human health conditions, including infection, autoimmune disorders, neurodegeneration, ageing, and cancer. Understanding these activation and regulatory mechanisms will inform the development of novel therapeutic strategies.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"193 ","pages":"Pages 10-25"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388198","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":"Phillyrin attenuates TGF-β1-induced pulmonary fibrosis by modulating the Nrf2/HO-1 pathway and epithelial-mesenchymal transition","authors":"Jinjin Yu ,&nbsp;Yang Liu ,&nbsp;Huixin Song ,&nbsp;Lingyi Liu ,&nbsp;Lingli Li ,&nbsp;Yuzhi Luo ,&nbsp;Yajing Ma ,&nbsp;Ruisi Zhu ,&nbsp;Xinyao Liu ,&nbsp;Songyuan Xia ,&nbsp;Dezhu Zhang ,&nbsp;Jianguo Meng ,&nbsp;Weifeng Li ,&nbsp;Xiaofeng Niu","doi":"10.1016/j.molimm.2026.03.003","DOIUrl":"10.1016/j.molimm.2026.03.003","url":null,"abstract":"<div><h3>Background</h3><div>Phillyrin (Phi), a natural lignan glycoside derived from Fructus Forsythiae, has been reported to exhibit anti-inflammatory and antioxidant activities. In this study, we investigated its therapeutic potential in a TGF-β1-induced model of epithelial-mesenchymal transition (EMT) in A549 human alveolar epithelial cells.</div></div><div><h3>Methods</h3><div>The mechanisms of Phi were initially predicted using network pharmacology and molecular docking. Subsequently, A549 cells were stimulated with TGF-β1 and treated with Phi. Key assessments included cell viability, inflammatory and oxidative stress markers, EMT-related proteins (E-cadherin, α-SMA, vimentin), and fibrosis-associated molecules (collagen I, fibronectin, MMP-2). The activation of the Nrf2/HO-1 antioxidant pathway was also examined.</div></div><div><h3>Results</h3><div>Phi significantly attenuated TGF-β1-induced EMT and fibrotic responses in A549 cells. It not only suppressed inflammatory cytokine production and oxidative stress but also restored epithelial marker expression and reduced mesenchymal and fibrotic protein levels. Moreover, Phi upregulated the Nrf2/HO-1 signaling pathway, enhancing cellular antioxidant capacity.</div></div><div><h3>Conclusion</h3><div>These findings suggest that Phi possesses potent anti-inflammatory, antioxidant, and anti-fibrotic properties, effectively inhibiting TGF-β1-driven EMT in alveolar epithelial cells. Phi may represent a promising therapeutic candidate for treating idiopathic pulmonary fibrosis and other fibrotic lung diseases.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"193 ","pages":"Pages 39-49"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388200","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":"m⁶A-modified circMELK regulates nasopharyngeal carcinoma progression via a YTHDF1/circMELK-miR-4775-HMGA2 feedback loop","authors":"Qiang Yi ,&nbsp;Kui Zhong ,&nbsp;Zheng Chen ,&nbsp;Xinting Ouyang ,&nbsp;Weijian Zhu ,&nbsp;Leifeng Liang ,&nbsp;Jinghua Zhong","doi":"10.1016/j.molimm.2026.03.002","DOIUrl":"10.1016/j.molimm.2026.03.002","url":null,"abstract":"<div><h3>Background</h3><div>Circular RNAs (circRNAs) are emerging regulators in tumor biology. However, their roles in nasopharyngeal carcinoma (NPC) remain poorly defined.</div></div><div><h3>Methods</h3><div>By analyzing GSE190271, we identified hsa_circ_0138742 (circMELK) as significantly upregulated in NPC. Functional assays in vitro and in vivo were performed to explore its biological role. Mechanistic studies included RIP, ChIP, RNA pull-down, dual-luciferase assays, and rescue experiments.</div></div><div><h3>Results</h3><div>circMELK was markedly elevated in NPC tissues and cells. Silencing circMELK inhibited NPC cell proliferation, migration, and invasion, while overexpression enhanced these malignant traits. Mechanistically, YTHDF1-mediated m6A modification serves as a key determinant for the cytoplasmic export of circMELK. There, circMELK acts as a ceRNA for miR-4775, relieving suppression of HMGA2. Elevated HMGA2 upregulates YTHDF1 by transcriptional activation, forming a YTHDF1/circMELK-miR-4775-HMGA2 positive feedback loop that drives epithelial–mesenchymal transition (EMT) and promotes metastasis.</div></div><div><h3>Conclusion</h3><div>circMELK promotes NPC progression via a novel m6A-dependent ceRNA regulatory loop. Targeting this axis may offer new therapeutic opportunities.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"193 ","pages":"Pages 50-67"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388201","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":"Mechanistic understanding of the protective effects of baicalein against the inflammatory response induced by Toxoplasma gondii in Ana-1 macrophages","authors":"XiaoJuan Wang,&nbsp;ZhengQing Yu,&nbsp;WeiYu Qi,&nbsp;YuChen Jiang,&nbsp;PingLong Yang,&nbsp;JiuSu Tu,&nbsp;YunNan Fang,&nbsp;Pan Zhou,&nbsp;Li Zhang","doi":"10.1016/j.molimm.2026.01.012","DOIUrl":"10.1016/j.molimm.2026.01.012","url":null,"abstract":"<div><div>Baicalein is an active flavonoid compound derived from Scutellaria baicalensis, a member of the Lamiaceae family, and has been widely reported to exhibit antioxidant, anti-inflammatory, and antimicrobial properties. However, the precise mechanisms underlying the anti-inflammatory effects of baicalein in <em>Toxoplasma gondii</em> infection-induced inflammation remain unclear. This study aims to systematically investigate the regulatory effects of baicalein on inflammation associated with <em>T. gondii</em> infection and its molecular mechanisms. The results indicate that baicalein significantly inhibits <em>T. gondii</em> proliferation, the production of inflammatory mediators and reduces the expression levels of pro-inflammatory cytokines. Further experiments revealed that baicalein effectively blocks the excessive activation of the cGAS-STING and NOD-like receptor signaling pathways in <em>T. gondii</em>-stimulated Ana-1 cells, thereby inhibiting the amplification of inflammatory signals. Additionally, baicalein enhances the expression of autophagy-related proteins, promoting autophagy and alleviating oxidative stress-induced cellular damage and inflammation. In conclusion, this study demonstrates that baicalein exerts its anti-inflammatory effects by activating autophagy and inhibiting the excessive activation of cGAS-STING and NOD-like receptor signaling pathways, effectively suppressing <em>T. gondii</em> infection-induced macrophage inflammation. These findings provide new theoretical insights into the potential therapeutic application of baicalein in infectious diseases.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"191 ","pages":"Pages 22-36"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157766","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":"Skin sensitisation to gluten in the absence and presence of atopic dermatitis drives changes in skin and systemic T cell phenotype composition in a rat model of food allergy","authors":"Jeppe Madura Larsen ,&nbsp;Sara Benazzouz ,&nbsp;Viktor Karl Wilhelm Törnblom ,&nbsp;Martin Iain Bahl ,&nbsp;Katrine Lindholm Bøgh","doi":"10.1016/j.molimm.2026.02.001","DOIUrl":"10.1016/j.molimm.2026.02.001","url":null,"abstract":"<div><div>Atopic dermatitis is associated with higher risk for developing immune-related comorbidities, including other atopic diseases like food allergy as well as certain infections, autoimmune diseases, and cancers. It remains largely unknown whether this increased risk of comorbidities is attributable to underlying AD-induced changes in non-skin immune composition and function beyond the exacerbation of allergic immune responses. Here Brown Norway rats were sensitised to hydrolysed gluten though the skin in the absence or presence of AD-like skin inflammation induced by topical application of MC903. T cell phenotype composition was analysed in skin, blood, and gut tissues by flow cytometry. M1/M2 differentiation and cytokine production by intraperitoneal-derived macrophages stimulated with bacteria, inflammatory cytokines, or food allergens were analysed using flow cytometry and ELISA. Gut microbiota composition was analysed by partial 16S rRNA gene sequencing. Sensitisation in both the absence and presence of induced AD-like skin inflammation was found to predominantly affect T cell phenotype composition in skin and blood immune compartments. This systemic effect of AD had a minor effect on M1/M2 differentiation but did not affect cytokine production by intraperitoneal-derived macrophages. These findings highlight some systemic effects of skin sensitisation and AD that potentially could affect non-skin immune responses.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"191 ","pages":"Pages 37-48"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157737","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":"Luteolin alleviates ox-LDL-induced endothelial cell inflammation, apoptosis and ferroptosis by inhibiting the NAT10/ALOX12 pathway","authors":"Biao Yang ,&nbsp;Hui Zhang ,&nbsp;Shi-jie Fang ,&nbsp;Yuan-zhi Liu ,&nbsp;Shuang-yue Zhang","doi":"10.1016/j.molimm.2026.01.011","DOIUrl":"10.1016/j.molimm.2026.01.011","url":null,"abstract":"<div><h3>Background</h3><div>Luteolin has been shown to have inhibitory effects on many human diseases, including atherosclerosis (AS). However, the specific role and underlying molecular mechanisms of luteolin in the progression of AS need to be further elucidated.</div></div><div><h3>Methods</h3><div>Oxidized-low density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) was used to construct AS models <em>in vitro</em>. Cell proliferation, inflammation, apoptosis and angiogenesis were examined by CCK8 assay, EdU assay, ELISA, flow cytometry, and tube formation assay. The mRNA and protein levels of arachidonate 12-lipoxygenase (ALOX12) and N-acetyltransferase 10 (NAT10) were tested by qRT-PCR and western blot. The regulation of NAT10 on ALOX12 was confirmed by ac4C-RIP assay, RIP assay and dual-luciferase reporter assay.</div></div><div><h3>Results</h3><div>Luteolin promoted cell proliferation and angiogenesis, while inhibited ox-LDL-induced HUVECs inflammation, apoptosis and ferroptosis. Luteolin targeted ALOX12 to reduce its expression. ALOX12 overexpression reversed the inhibitory effect of luteolin on ox-LDL-induced HUVECs injury. NAT10 promoted the ac4C modification of ALOX12 to increase its expression. NAT10 knockdown alleviated ox-LDL-induced HUVECs injury by downregulating ALOX12, and the protective effect of luteolin against ox-LDL-induced HUVECs injury could also be reversed by NAT10 overexpression.</div></div><div><h3>Conclusion</h3><div>Luteolin may inhibit ox-LDL-induced endothelial cell injury by suppressing NAT10-mediated the ac4C modification of ALOX12, thereby alleviating the progression of AS.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"191 ","pages":"Pages 1-9"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098873","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":"Sophora tonkinensis reprograms tumor-associated macrophages to M1-like phenotype and exerts anti-hepatocellular carcinoma effects","authors":"Siqi Huang ,&nbsp;Jincai Wen ,&nbsp;Xiaoyan Chen ,&nbsp;Xianling Wang ,&nbsp;Yuanyuan Guo ,&nbsp;Lu liu ,&nbsp;Caiping He ,&nbsp;Zongliang Lu ,&nbsp;Ang Huang ,&nbsp;Xiaoyan Zhan ,&nbsp;Jun Zhao ,&nbsp;Xiaohe Xiao ,&nbsp;Zhaofang Bai","doi":"10.1016/j.molimm.2026.02.003","DOIUrl":"10.1016/j.molimm.2026.02.003","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Sophora tonkinensis</em> radix et rhizoma is a medicinal herb traditionally used to treat inflammatory diseases and various types of cancer, previous phytochemistry studies have identified abundant alkaloids and flavonoids as the major bioactive components with anti-inflammatory, anti-tumor, hepatoprotective and immunomodulatory pharmacological effects, but their effects on Tumor-associated macrophages (TAMs) and the tumor immune microenvironment have not been systematically explored.</div></div><div><h3>Aim of the study</h3><div>This work aimed to establish whether a standardized extract of Sophora tonkinensis (STE) can halt IL-4-driven M2 macrophage polarization, reprogram established M2-like tumor-associated macrophages toward a pro-inflammatory M1-like phenotype, and clarify the underlying molecular mechanisms and <em>in vivo</em> efficacy of these immunomodulatory actions.</div></div><div><h3>Materials and methods</h3><div>Bone-marrow-derived macrophages (BMDMs) were polarized to an M2 phenotype and subsequently treated with STE. Expression of the M1/M2 markers Arg-1, CD206, iNOS, and CD86 in these macrophages was quantified by immunoblotting, qPCR, and flow cytometry. The impact of STE-pretreated M2-conditioned medium on the proliferation, migration, and invasion of Hepa 1–6 cells was then examined. H22 cells were subcutaneously inoculated into Balb/c mice to assess STE’s effects on the macrophage landscape within the tumor immune microenvironment and to evaluate its antitumor efficacy.</div></div><div><h3>Results</h3><div>STE dose-dependently suppressed IL-4–induced Arg-1 and CD206 while up-regulating iNOS and CD86, indicating a blockade of M2 polarization and a shift toward an M1 signature. Mechanistically, STE markedly increased JAK1 and STAT1 phosphorylation. Functionally, it potently inhibited invasion and migration of Hepa 1–6 cells. In tumor-bearing mice, robust suppression of tumor growth was accompanied by a pronounced reduction in M2-like TAMs and a reciprocal increase in M1-like macrophages within the tumor microenvironment.</div></div><div><h3>Conclusion</h3><div>STE reprograms TAMs via the JAK1/STAT1 axis and exhibits robust antitumor activity, underscoring its promise as a natural, macrophage-targeted immunotherapeutic that warrants further investigation for integration into cancer treatment strategies.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"191 ","pages":"Pages 49-59"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157825","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}