International immunopharmacology最新文献

{"title":"Targeting HSPB1 inhibits tumor growth and abrogates Treg-mediated tumor immunosuppression","authors":"Qi Hu ,&nbsp;Yang Lu ,&nbsp;Xiaolan Zhong ,&nbsp;Peng Huang ,&nbsp;Lisheng Zheng ,&nbsp;Bing-Hua Jiang ,&nbsp;Wanglin Li ,&nbsp;Song Guo Zheng","doi":"10.1016/j.intimp.2026.116333","DOIUrl":"10.1016/j.intimp.2026.116333","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer exhibits limited responsiveness to immune-checkpoint blockade, primarily because an elevated intratumoral Treg/CD8⁺ T-cell ratio extinguishes antitumor immunity. The molecular determinants that lock this immunosuppressive balance are unknown.</div></div><div><h3>Methods</h3><div>We integrated single-cell RNA-seq, TCGA WGCNA, and spatial transcriptomics to nominate candidate regulators of the Treg/CD8⁺ ratio. CRISPR-Cas9 was used to generate HSPB1-knockout MC38 and SW480 cell lines. Subcutaneous models were employed to assess tumor growth. Immune profiling was performed by multiparametric flow cytometry; mechanistic dissection combined bulk RNA-seq, Transwell assays, western blot and <em>in vitro</em> T-cell polarization systems.</div></div><div><h3>Results</h3><div>Single-cell profiling and TCGA WGCNA analyze identified HSPB1 as a putative determinant of the intratumoral Treg/CD8⁺ T-cell ratio, and survival analysis showed its prognostic relevance in CRC. Spatial transcriptomics revealed colocalization of HSPB1-expressing tumor cells with Tregs. Subcutaneous tumor models demonstrated that HSPB1 genetic deletion or pharmacological inhibition markedly suppressed tumor growth and abolish the Treg-dominated microenvironment. <em>In vitro</em> polarization assays confirmed that targeting HSPB1 selectively restrains Treg differentiation without affecting Th17. Integrated transcriptomic and functional assays further elucidated that HSPB1 orchestrates Treg recruitment via the CCL20–CCR6 axis, thereby shaping the immunosuppressive milieu within colorectal tumors.</div></div><div><h3>Conclusions</h3><div>Targeting HSPB1 exerts dual anti-tumor effects: it directly suppresses neoplastic proliferation and simultaneously alleviates Treg-mediated immunosuppression within the tumor microenvironment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116333"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165221","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":"Circulating EVs are involved in myocardial tissue PANoptosis regulation by delivering miR-16-5p to treat myocardial injury","authors":"Meijing Zhang,&nbsp;Changzai Liang,&nbsp;Teng Ma,&nbsp;Yalei Han,&nbsp;Meng Zhang","doi":"10.1016/j.intimp.2026.116272","DOIUrl":"10.1016/j.intimp.2026.116272","url":null,"abstract":"<div><h3>Background</h3><div>Acute myocardial infarction (AMI) is a leading global cause of death, with extracellular vesicles (EVs) emerging as potential therapeutic mediators. However, the mechanisms by which circulating EVs from different sources influence myocardial injury remain unclear.</div></div><div><h3>Method</h3><div>Circulating EVs from AMI patients (AMI-EVs) and healthy controls (N-EVs) were isolated. In vitro assays (CCK8, EdU, flow cytometry, wound healing, angiogenesis) evaluated their effects on cardiomyocyte/endothelial cell proliferation, apoptosis, migration, and tube formation. Immune cell infiltration and immunoglobulin levels in myocardial injury patients were analyzed. Microarray and qPCR identified differentially expressed miRNAs in EVs. CYP1B1, predicted as a target of miR-16-5p via bioinformatics, was validated using dual-luciferase reporter and RNA co-immunoprecipitation. An ischemia-reperfusion (I/R) mouse model assessed EV effects on myocardial injury and PANoptosis.</div></div><div><h3>Result</h3><div>N-EVs alleviated I/R-induced myocardial injury in vivo and protected cardiomyocytes/endothelial cells from H2O2-induced damage in vitro. Patients with myocardial injury exhibited IgG deposits, immune cell infiltration, and elevated IgG1/IgG3 levels. N-EVs promoted angiogenesis and cardiomyocyte proliferation while suppressing PANoptosis (combined apoptosis, necroptosis, pyroptosis). Mechanistically, miR-16-5p was enriched in N-EVs and directly targeted CYP1B1, inhibiting its expression and downstream PANoptosis pathways.</div></div><div><h3>Conclusion</h3><div>N-EVs mitigate myocardial injury by delivering miR-16-5p to suppress CYP1B1-mediated PANoptosis, highlighting their role in intercellular communication and therapeutic potential for AMI. This study provides insights into EV-based strategies for cardiac repair and fibrosis prevention.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116272"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157095","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":"TREM1 as a master regulator of mitophagy-pyroptosis crosstalk in myocardial infarction: A dual-target strategy for precision therapy","authors":"Xingwei Hu ,&nbsp;Xiang He ,&nbsp;Miaomiao Xiang ,&nbsp;Yan Wang ,&nbsp;Shuai Ma ,&nbsp;Mengsha Li ,&nbsp;Yi Ma","doi":"10.1016/j.intimp.2026.116353","DOIUrl":"10.1016/j.intimp.2026.116353","url":null,"abstract":"<div><div>Myocardial infarction (MI), a global health crisis driven by dysregulated immune responses and genetic-environmental interplay, remains inadequately addressed by current therapies targeting programmed cell death (PCD). While apoptosis, mitophagy, and pyroptosis collectively orchestrate MI progression. Emerging evidence underscores the pivotal roles of mitophagy and pyroptosis in regulating NLRP3 inflammasome activation, however, the crosstalk between these processes remains a critical unresolved question in cardiovascular immunology. Here, we identify Triggering Receptor Expressed on Myeloid cells 1 (TREM1) as a central molecular nexus governing this axis. Leveraging integrative bioinformatics analysis of the GSE66360 dataset combined with functional validation in macrophage-specific and MI rodent models, we demonstrate that TREM1 overexpression suppresses PINK1/Parkin-mediated mitophagy while paradoxically exacerbating NLRP3-dependent pyroptosis. Moreover, TREM1 knockdown significantly improved post-MI cardiac function and attenuated fibrotic remodeling. These findings establish TREM1 as both a prognostic biomarker for MI and a pleiotropic therapeutic target capable of simultaneously dampening NLRP3 inflammasome hyperactivation and promoting cardiac functional recovery.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116353"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179439","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":"Influence of syringic acid on schizophrenia in mice: Modulation of PI3K/AKT1/GSK3β signaling pathway, galectin-3 and MBP","authors":"Abeer Salama ,&nbsp;Sahar Abd Elwahab ,&nbsp;Amany A. El-Fadaly","doi":"10.1016/j.intimp.2026.116367","DOIUrl":"10.1016/j.intimp.2026.116367","url":null,"abstract":"<div><div>Schizophrenia is a highly debilitating mental disorder characterized by a variety of neurodevelopmental and behavioral issues. There is mounting evidence that neuroinflammation and myelin deficiency are the coexisting pathological features that lead to schizophrenia. Thus, the current work investigated the therapeutic potential of syringic acid (SA) in ameliorating neuroinflammation and demyelination in a mouse model of cuprizone (CPZ)-induced schizophrenia. Schizophrenia in mice was induced by 0.2% CPZ in diet for 6 weeks. Male Swiss mice were randomly divided into four groups: 1st group: Normal control group received normal chow for 6 weeks, 2nd group: CPZ, 3rd Group: Mice received CPZ + SA (50 mg/kg; orally). 4th group: Mice received CPZ + SA (100 mg/kg; orally). Our results showed that CPZ induced behavioral, biochemical, molecular and histopathological changes, while SA significantly alleviated behavioral abnormalities induced by CPZ. Furthermore, SA increased Pi form of glutathione-S-transferase (GST-π), myelin basic protein (MBP), neuregulin-1 (NRG-1), protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3k), and protein kinase B (Akt1). Additionally, it lessened glial fibrillary acidic protein (GFAP), galectin-3, glycogen synthase kinase 3 beta (GSK-3β), and tumor necrosis factor-α (TNF-α<strong>)</strong>. Moreover, SA relieved histopathological alterations in the brain induced by CPZ. The above findings suggest that SA could ameliorate CPZ-induced psychotic symptoms in mice via suppressing neuroinflammation and promoting myelin integrity, perhaps providing further benefits to people suffering from schizophrenia.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116367"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192734","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":"Comparative evaluation of two platforms delivering RSV mRNA vaccines expressing modified extracellular domain of G glycoprotein in mice","authors":"Ruiwen Han ,&nbsp;Aiyi Zhang ,&nbsp;Yujie Jiang ,&nbsp;Siyu Yin ,&nbsp;Tangqi Wang ,&nbsp;Xinwei Gao ,&nbsp;Yao Deng ,&nbsp;Yu Li ,&nbsp;Wenjie Tan","doi":"10.1016/j.intimp.2026.116369","DOIUrl":"10.1016/j.intimp.2026.116369","url":null,"abstract":"<div><div>Respiratory syncytial virus (RSV) is the leading cause of respiratory infections in infants, young children, and elderly people worldwide. Developing a safe and broadly effective vaccine remains a critical and unmet public health need. This study comparatively evaluated the immunogenicity and protective efficacy of respiratory syncytial virus (RSV) mRNA vaccines expressing a modified G protein extracellular domain (G^ecto), delivered via either lipid nanoparticle (LNP) or lipid-polymer hybrid (LPP) platforms. Both RSV G^ecto-mRNA elicited robust humoral and cellular immunity in mice. Although the humoral immunity in both groups showed a Th2 bias, the advantage of the LNP platform lies in its ability to simultaneously trigger potent humoral and Th1-type cellular immunity. Comparing the two groups, The LNP group elicited a stronger Th1-biased cellular response, manifested by high expression of cytokines such as IL-2 and TNF-α in CD4⁺T cells, and the production of higher neutralizing antibody titers against A/B subtypes of RSV strains than the LPP group,which elicited slightly higher Th2 bias IgG antibody titers. Viral challenge confirmed that both groups provided effective cross-protection against RSV A2 and B9320, significantly reducing lung viral load and histopathology, with comparable protective efficacy.These findings demonstrate that both platforms enabled robust delivery of the RSV G^ecto-mRNA vaccine and generated cross-protective immunity, albeit with divergent response characteristics. These results inform the selection of RSV vaccine delivery platforms aimed at distinct immune correlates of protection.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116369"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192736","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":"The mechanism study of isoorientin regulating neuroinflammation after subarachnoid hemorrhage through AKT/GSK3β","authors":"Yong-Xiao Jiang ,&nbsp;Meng-Xiao Xu ,&nbsp;Yue Cui ,&nbsp;Jie Wang ,&nbsp;Xun-Zhi Liu ,&nbsp;Peng-Fei Ding ,&nbsp;Si-Min Zhi ,&nbsp;Jia-Tong Zhang ,&nbsp;Zheng Peng ,&nbsp;Xiao-Jian Li ,&nbsp;Xiang-Xin Chen ,&nbsp;Chun-Hua Hang ,&nbsp;Ling-Yun Wu ,&nbsp;Wei Li","doi":"10.1016/j.intimp.2026.116299","DOIUrl":"10.1016/j.intimp.2026.116299","url":null,"abstract":"<div><h3>Background</h3><div>Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease with high incidence and mortality rates, often associated with aneurysm rupture. Neuroinflammation, primarily mediated by microglial activation, is a critical process in the secondary injury following SAH. Despite extensive research, current Western medicine treatments have shown limited efficacy in mitigating neuroinflammation caused by microglia. In contrast, traditional Chinese medicine has garnered increasing attention for its anti-inflammatory properties. Isoorientin, a flavonoid compound, has demonstrated anti-inflammatory and antioxidant effects in various diseases. We hypothesize that isoorientin may inhibit microglia-induced neuroinflammation after SAH through the AKT/GSK3β pathway.</div></div><div><h3>Purpose</h3><div>To elucidate whether isoorientin can regulate neuroinflammation following subarachnoid hemorrhage via the AKT/GSK3β pathway.</div></div><div><h3>Methods</h3><div>We established in vitro and in vivo SAH models using hemoglobin and blood injection methods, respectively. The regulatory effects of isoorientin on neuroinflammation were investigated using Western blotting (WB), quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining (IF). Network pharmacology and molecular docking studies were conducted to explore the potential mechanisms. Additionally, the AKT inhibitor (MK2206) was employed to investigate its effects on the AKT/GSK3β pathway and neurological function after SAH. Neuroprotective effects were assessed using neurological function scores, open field tests, and rotarod tests.</div></div><div><h3>Results</h3><div>Isoorientin significantly inhibited the mRNA expression levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and promoted the expression levels of anti-inflammatory cytokines (CD206, IL-4, and IL-10). It facilitated the transformation of microglia from the M1 (pro-inflammatory) to the M2 (anti-inflammatory) phenotype. Further experiments revealed that isoorientin increased the expression of p-AKT protein in microglial cells, leading to the inactivation of GSK3β and upregulation of p-GSK3β protein, thereby suppressing neuroinflammation. However, these effects were reversed upon the addition of the AKT inhibitor (MK2206). In vivo experiments demonstrated that isoorientin improved short-term neurological functions, including motor functions, balance, and coordination abilities.</div></div><div><h3>Conclusion</h3><div>This study provides compelling evidence that isoorientin exerts neuroprotective effects by regulating the AKT/GSK3β pathway, which may play a crucial role in mitigating neuroinflammation and neurological dysfunction after SAH. Isoorientin holds promise as a valuable therapeutic candidate for SAH treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116299"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165201","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":"CD138-targeted bispecific protein engager-armed T cells exhibit potent and selective cytotoxicity against multiple myeloma cells","authors":"Pucharee Songprakhon ,&nbsp;Piriya Luangwattananun ,&nbsp;Kornkan Choomee ,&nbsp;Nunghathai Sawasdee ,&nbsp;Chalermchai Somboonpatarakun ,&nbsp;Thaweesak Chieochansin ,&nbsp;Sanya Sukpanichnant ,&nbsp;Mutita Junking ,&nbsp;Seiji Okada ,&nbsp;Pa-Thai Yenchitsomanus","doi":"10.1016/j.intimp.2026.116295","DOIUrl":"10.1016/j.intimp.2026.116295","url":null,"abstract":"<div><div>Multiple myeloma (MM) is a hematologic malignancy that remains incurable, with most patients eventually relapsing or developing resistance to available therapies. Bispecific T cell engagers (BiTEs) have shown promise by redirecting T cells to target and kill tumor cells; however, their clinical application is hindered by a short <em>in vivo</em> half-life, the need for high dosing, and treatment-related toxicities. To address these limitations, bispecific protein engager-armed T cells (BATs) have been developed as a novel cell-based immunotherapy platform that enhances antigen specificity and <em>in vivo</em> persistence. In this study, we evaluated the antitumor efficacy of BATs targeting CD138, a heparan sulfate proteoglycan highly expressed on MM cells and associated with disease progression. BATs were generated by arming T cells with an anti-CD138 × anti-CD3 bispecific protein engager (BiPE), and their antitumor activity was assessed through counting bead technique and flow cytometry. CD138-specific BATs exhibited potent cytotoxicity against CD138-positive MM.1R cells, achieving up to 89.62 ± 2.22% cell lysis after 48 h of co-culture, significantly surpassing the activity of unarmed T cells (33.04 ± 6.57% lysis). Additionally, BATs induced robust expression of interleukin-2 (IL-2) cytokine and cytolytic mediators, including perforin, granzyme A/B, soluble Fas ligand (sFasL), and TNF-α, indicating effective antigen-specific activation. Importantly, pro-inflammatory cytokines such as IL-6, IL-10, and IFN-γ remained at low levels, suggesting a favorable safety profile. These findings support the therapeutic potential of CD138-targeted BATs as a promising and potentially safer cellular immunotherapy for the treatment of MM.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116295"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192737","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":"Pancreas-brain axis: exploring the pathogenic mechanisms of pancreatic encephalopathy","authors":"Ni-Nan Dai ,&nbsp;Zheng-Guang Geng ,&nbsp;Jing Wang ,&nbsp;Xiao-Li Bu ,&nbsp;Ming-Yang Gong ,&nbsp;Chang Qin ,&nbsp;Yu Zhang ,&nbsp;Xiao-Yun Fu ,&nbsp;Bao Fu","doi":"10.1016/j.intimp.2026.116332","DOIUrl":"10.1016/j.intimp.2026.116332","url":null,"abstract":"<div><div>Pancreatic encephalopathy (PE) is a severe yet under-recognized neurological complication of acute pancreatitis, characterized by disturbances in consciousness, cognitive impairment, and high mortality. Recent epidemiological evidence indicates that PE occurs more frequently than previously appreciated, particularly in patients with severe disease. The pathogenesis of PE is multifactorial and involves pancreatic enzyme-mediated toxicity, systemic inflammation, metabolic dysregulation, and blood-brain barrier disruption.</div><div>Emerging studies support the concept of a <strong>bidirectional pancreas–brain axis</strong>, through which pancreatic injury signals are transmitted to the central nervous system via integrated neural, endocrine, immune, and microbiota-related pathways. This review synthesizes the current evidence on the molecular, cellular, and network-level mechanisms underlying PE, with a focus on neuro-glial-immune interactions, excitotoxicity, mitochondrial dysfunction, and neuroinflammation. We summarize advances in diagnostic biomarkers and discuss the translational potential of emerging therapeutic strategies, including neuromodulation, mitochondrial protection, and short-chain fatty acid supplementation.</div><div>By providing an integrated framework of the pancreas–brain axis, this review aims to clarify the pathophysiology of PE and highlight future directions for diagnostic and therapeutic development.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116332"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192732","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":"Tuning tissue-resident memory T cells to fuel cancer immunotherapy","authors":"Yao Zhang ,&nbsp;Yi-Xuan Fang ,&nbsp;Yao Xiao,&nbsp;Shu-Jin Li,&nbsp;Zhi-Jun Sun","doi":"10.1016/j.intimp.2026.116308","DOIUrl":"10.1016/j.intimp.2026.116308","url":null,"abstract":"<div><div>As the threat of cancer to humanity continues to intensify, immunotherapy has emerged as a promising novel approach in cancer treatment. However, the efficacy of existing immunotherapy varies and needs to be improved urgently. Tissue-resident memory T (T_RM) cells, a subset of T cells, have typical tissue-residency characteristics and formidable antitumor potential, which may be a latent enhancer for cancer immunotherapy. Besides, T_RM cells are more readily modulated in the process of immunotherapy, compared to other T cell subsets present in the tumor microenvironment. This review summarizes the molecular phenotypes of T_RM cells, introduces the relationship between T_RM cells and cancer immunology, and proposes a range of potential immunotherapeutic strategies targeting T_RM cells. Particularly, this review critically evaluates current clinical strategies and research aimed at modulating T_RM cells. These insights are intended to provide new directions for tuning T_RM for advancing cancer immunotherapy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116308"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179429","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":"Sanguinarine inhibits deep venous thrombosis by suppressing platelets TLR4 and reducing the release of platelets-derived HMGB1","authors":"Dan Shu ,&nbsp;Ying Zhu ,&nbsp;Xin Yi ,&nbsp;Yi Fan ,&nbsp;Xia-yu Wu ,&nbsp;Fang Guo ,&nbsp;Xiang-Bin Zeng ,&nbsp;Meng Lu ,&nbsp;Fu-qin He ,&nbsp;Xue Gong ,&nbsp;Yu-min Zhang ,&nbsp;Yong-jun Liu ,&nbsp;Zhang-Yin Ming","doi":"10.1016/j.intimp.2026.116322","DOIUrl":"10.1016/j.intimp.2026.116322","url":null,"abstract":"<div><h3>Background</h3><div>Deep vein thrombosis (DVT) is a common cardiovascular disease associated with considerable health burden, involved in inflammatory. Beside of coagulation factor, platelets also play a pivotal role in DVT. However, strategy target to platelets in DVT was limited. Sanguinarine (SA), an active ingredient extracted from poppy plants, has shown promising anti-platelets effect, whereas its potential therapeutic mechanism on DVT remains largely unknown. We aimed to investigate the therapeutic effects and the underlying mechanisms of SA on DVT.</div></div><div><h3>Methods</h3><div>Firstly, the inferior vena cava (IVC) models were utilized to modify DVT progress. Then, network pharmacology, molecular simulation, flow cytometry and western blot were employed to elucidate the mechanisms underlying. Also, loxP-Cre transgenic mice were used to confirm the targetability of SA in vivo. Finally, transwell assay and immunofluorescence staining was used to detect neutrophils migration and neutrophil extracellular traps (NETs) formation.</div></div><div><h3>Results</h3><div>We found that SA administration dose-dependently inhibited DVT formation, and decreased NETs formation in vivo. Molecular simulation and cellular thermal shift assay suggested that SA directly binds to TLR4/MD2. Furthermore, the antithrombotic effects of SA disappeared in platelets specific TLR4 deficient mice. Mechanistically, SA suppressed TLR4/αIIbβ3 signaling and reduced HMGB1 externalization in platelets. Moreover, platelets TLR4 activation induced neutrophils recruitment and NETs formation by releasing HMGB1, SA abolished this progress.</div></div><div><h3>Conclusion</h3><div>In summary, SA mitigates DVT by inhibiting platelets-derived HMGB1 release through the inhibition of TLR4 signaling. This suggests that SA holds promise as a therapeutic agent for DVT.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116322"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165179","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}