International immunopharmacology最新文献

{"title":"Role of reactive oxygen species in polycystic ovary syndrome: signalling pathways, mechanisms, and traditional Chinese medicine treatment strategies","authors":"Ziyi Wang ,&nbsp;Shuyuan Liu ,&nbsp;Mengyao Gao ,&nbsp;Ying Shen ,&nbsp;Miao Sun ,&nbsp;Songli Hao","doi":"10.1016/j.intimp.2026.116251","DOIUrl":"10.1016/j.intimp.2026.116251","url":null,"abstract":"<div><div>The biological role reactive oxygen species (ROS), both as byproduct of cellular respiration and as crucial secondary messengers, has been extensively acknowledged in scientific literature. Key ROS-generating enzymes and organelles, including mitochondria, NADPH oxidase, and the endoplasmic reticulum, have been found closely linked to the regulation of metabolic processes. An imbalance between oxidative and antioxidant systems, resulting from abnormal ROS production and leading to oxidative stress (OS), has been implicated as a significant pathogenic in a variety of diseases, such as polycystic ovary syndrome (PCOS). PCOS is a prevalent endocrine disorder that adversely affects reproductive health and metabolic homeostasis in women of reproductive age. This review provides a systematic examination of the three primary sources of ROS production, and explores the mechanisms through which excessive ROS production triggers the dysregulation of key signalling pathways. These pathways are central to the fundamental pathological features of PCOS, such as ovulatory dysfunction, obesity phenotype, insulin resistance, and hyperandrogenism, with a specific emphasis on the interactions within ROS signalling pathways. Grounded in the holistic regulation principles of Chinese medicine and targeting the core signalling pathway as the intervention focal point, we propose a comprehensive intervention strategy. This strategy incorporates natural compounds, herbal compounds, acupuncture, dietary supplements, and other therapeutic approaches, which will provide a new theoretical framework and research direction for enhancing the clinical management of PCOS.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116251"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037432","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":"Methamphetamine regulates microglial polarization and glycolytic activity to promote Parkinson's disease through the LIPH/LPA/PI3K/AKT signaling axis","authors":"Yanghong Zou ,&nbsp;Chunhai Zhang ,&nbsp;Hui Bian ,&nbsp;Hao Fan ,&nbsp;Ailan Pang ,&nbsp;Yingwang Yuan ,&nbsp;Jinghui Li ,&nbsp;Xin Geng","doi":"10.1016/j.intimp.2026.116306","DOIUrl":"10.1016/j.intimp.2026.116306","url":null,"abstract":"<div><h3>Background</h3><div>The abuse of methamphetamine (METH) is associated with an increased risk of Parkinson's disease (PD), whereas microglial polarization and glucose metabolism disorders are closely related to the progression of PD. This study aimed to investigate the specific molecular mechanism underlying the promotion of PD progression by METH through the regulation of microglial polarization and glycolysis.</div><div><strong>Methods:</strong> METH-induced C57BL/6 mice and BV2 cells were used to construct PD-like neurotoxicity animal and cell models for experimental investigation. Behavioral tests, immunohistochemistry and Nissl staining were used to assess the behavioral ability and neuronal damage of the animals. The levels of related proteins, inflammatory cytokines and glycolysis were detected using immunofluorescence, ELISA, Western blotting, and CCK-8 assays.</div><div><strong>Results:</strong> METH treatment significantly promoted behavioral disorders in PD mice, reduced the number of TH-positive neurons, and aggravated neuronal damage in the substantia nigra (SN). In addition, METH decreased the M2 marker proteins Arg-1 and CD206 and increased the M1 marker proteins iNOS and CD86; the proinflammatory cytokines TNF-α, IL-β, and IL-6; and glucose uptake, glucose consumption and lactic acid production, thus promoting M1 polarization and glycolytic activity in BV2 cells. In terms of the underlying molecular mechanism, METH treatment significantly increased the level of LPA. METH promotes LPA expression via upregulation of LIPH expression, and activates the PI3K/AKT pathway. Knockdown of LIPH or treatment with BrP-LPA reduces the ability of METH to promote M1 microglial polarization and glycolytic activity. Furthermore, the addition of the PI3K/AKT signaling pathway activator 740 Y<img>P weakened the inhibitory effect of BrP-LPA on the above process.</div><div><strong>Conclusion:</strong> METH may promote M1 polarization and glycolytic activity in microglia by activating LIPH/LPA/PI3K/AKT signaling, thus promoting the progression of PD.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116306"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105154","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":"FcRn alleviates mycobacterium-induced lung injury by triggering YBX1-mediated autophagy","authors":"Yanan Xu ,&nbsp;Zhaoqian Gong ,&nbsp;Jialin Yu ,&nbsp;Jiamei Zhang ,&nbsp;Guangcun Deng ,&nbsp;Xiaoling Wu","doi":"10.1016/j.intimp.2026.116310","DOIUrl":"10.1016/j.intimp.2026.116310","url":null,"abstract":"<div><div>The neonatal fc receptor (FcRn) is indispensable in sustaining IgG homeostasis. Recently, the potential role of FcRn in infectious diseases has attracted more attention. However, the function of FcRn in tuberculosis is unclear. The present study aimed to investigate the role of FcRn in regulating BCG infection-induced autophagy in vitro and vivo. FCGRT knockout mice and FcRn knockdown cells were constructed by CRISPR/Cas9 and small interfering RNA. The related indicators of autophagy were detected by transmission electron microscopy, flow cytometry, and western blot. The proteins interacting with FcRn were screened by immunoprecipitation (IP) and mass spectrometry (MS). The results showed more lung injury and less autophagy marker expression in the KO-FcRn mice lungs than wild type (WT) mice after BCG infection (<em>p</em> &lt; 0.01). Meanwhile, si-FcRn restrained BCG-induced macrophage autophagy by activating the PI3K/AKT/m-TOR pathway. Furthermore, FcRn was confirmed to interact with the Y-box binding protein 1 (YBX1) and promote its nuclear translocation. Hence, the current study proved that FcRn protects against BCG-induced lung injury by triggering YBX1-mediated autophagy and suppressing the PI3K /AKT/mTOR signaling pathway. These findings present a novel understanding of the immune role of FcRn in treating and preventing tuberculosis</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116310"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113117","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":"Polysialylated CD56 drives immune evasion in clear cell renal cell carcinoma via engagement of the Siglec-7 checkpoint on CD8+ T cells","authors":"Yuli Jian ,&nbsp;Li Gong ,&nbsp;Ling Tang ,&nbsp;Moyuan Zhang ,&nbsp;Shiya You ,&nbsp;Zhilin Li ,&nbsp;Mingxin Wu ,&nbsp;Shuang Wang ,&nbsp;Zheng Zhu ,&nbsp;Deyong Yang ,&nbsp;Shujing Wang","doi":"10.1016/j.intimp.2026.116302","DOIUrl":"10.1016/j.intimp.2026.116302","url":null,"abstract":"<div><div>Immune checkpoint blockade has revolutionized clear cell renal cell carcinoma (ccRCC) treatment, yet therapeutic resistance remains a significant clinical challenge. Aberrant glycosylation contributes to tumor progression and immunotherapy resistance. However, the specific glycans and corresponding immunomodulatory receptors involved in ccRCC remain poorly understood. Here, we identify polysialylated CD56 (PSA-CD56) as a key glycan-mediated immune regulator that drives immunosuppression in ccRCC through engagement of Siglec-7. Elevated PSA-CD56 expression was inversely correlated with CD8⁺ T cell infiltration and predicted inferior responses to immunotherapy. Genetic ablation of NCAM1 (encoding CD56) in renal epithelial cells suppressed tumor growth and enhanced CD4⁺ and CD8⁺ T cell infiltration <em>in vivo</em>. Mechanistically, PSA-CD56, but not its non-polysialylated form, directly bound to Siglec-7 on CD8⁺ T cells, suppressing the production of IFN-γ and TNF-α and promoting T cell apoptosis. Importantly, blocking the PSA-CD56/Siglec-7 interaction with specific antibodies restored T cell effector functions and triggered apoptosis of ccRCC cells. Our study unveils the PSA-CD56/Siglec-7 axis as a novel glyco-immune checkpoint, which represents a promising target for therapeutic interventions in ccRCC.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116302"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124976","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":"Corrigendum to “TREM2 regulates neuroinflammation by SYK-dependent inhibition of BTK activation to improve perioperative neurocognitive dysfunction” [Int. Immunopharmacol. 173 (2026) 116269]","authors":"Kaiyun Zhang ,&nbsp;Wenying Chi ,&nbsp;Junzuo Guo ,&nbsp;Yaru Huang ,&nbsp;Zhe Zhang ,&nbsp;Xinlei Guo ,&nbsp;Bowen Zhang ,&nbsp;Fanjun Meng","doi":"10.1016/j.intimp.2026.116311","DOIUrl":"10.1016/j.intimp.2026.116311","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116311"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131757","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":"MD2 suppresses anaplastic thyroid Cancer progression by reprogramming macrophages via USP15-mediated FHL1 Deubiquitination","authors":"Qilu Fang ,&nbsp;Neng Lv ,&nbsp;Jia Wang ,&nbsp;Shuwei Yu ,&nbsp;Haiying Ding ,&nbsp;Jun Cao ,&nbsp;Wenxiu Xin","doi":"10.1016/j.intimp.2026.116317","DOIUrl":"10.1016/j.intimp.2026.116317","url":null,"abstract":"<div><div>Tumor-associated macrophages (TAMs), highly heterogeneous cells within the tumor microenvironment, can be broadly classified into anti-tumor M1 and pro-tumor M2 phenotypes. Myeloid differentiation protein 2 (MD2), a key immune regulator, has been demonstrated to modulate macrophage inflammatory responses. However, its involvement in TAM reprogramming and the subsequent impact on anaplastic thyroid cancer (ATC) progression remains unclear. In this study, we observed that ATC cells promote macrophage polarization toward the M2 phenotype, accompanied by reduced MD2 expression. Notably, MD2 upregulated the expression of USP15, which was subsequently proved to interact with four and a half LIM domains protein 1 (FHL1) and mediated its deubiquitination, leading to STAT3 inactivation and promoting macrophage polarization toward the M1 phenotype. Furthermore, overexpression of MD2 in macrophages significantly suppressed tumor growth and metastasis through TAM reprogramming. Collectively, these findings highlight a critical role of MD2 in regulating TAM polarization and suggest macrophage-targeted modulation of MD2 as a potential therapeutic strategy for ATC.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116317"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137345","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":"IGF-1 ameliorates the blood brain barrier disruption induced by the neonatal hypoxia-ischemia","authors":"Rui Zhong ,&nbsp;Haiqing Huang ,&nbsp;Jiayi Liang ,&nbsp;Wei Lai ,&nbsp;Yingyin Tan ,&nbsp;Wanxia Liu ,&nbsp;Baohong Yuan ,&nbsp;Zhenhui He ,&nbsp;Yanli Tang ,&nbsp;Tao Liu ,&nbsp;Hui Yin","doi":"10.1016/j.intimp.2026.116323","DOIUrl":"10.1016/j.intimp.2026.116323","url":null,"abstract":"<div><div>Neonatal hypoxic-ischemic encephalopathy (HIE) disrupts the blood-brain barrier (BBB) and destroys nascent vessels, thereby amplifying parenchymal loss and chronic neurological disability. Restoring a competent cerebrovasculature is therefore a critical therapeutic goal. Insulin-like growth factor-1 (IGF-1) is already recognized as a neurotrophic factor whose circulating levels correlate with HIE severity and long-term outcome, yet its capacity to drive vascular repair after the insult remains incompletely defined. This study investigated the role of exogenous IGF-1 in BBB repair in neonatal mouse post HI. Our results showed that IGF-1 receptor (IGF-1R) existed on the surface of endothelial cells, which was further upregulated in response to HI challenge. Administration of exogenous IGF-1 apparently attenuated BBB disruption concomitant with a marked enhancement of angiogenesis within the injured cerebral parenchyma. On the contrary, inhibition of the IGF-1R abrogated IGF-1-mediated proangiogenic effects. More importantly, activation of the IGF-1/IGF-1R axis promotes revascularization dependent on upregulation of AKT/eNOS signaling. All together, these findings indicate that IGF-1/IGF-1R axis may represent a potential therapeutic target for blood-brain barrier repair in neonatal HI injury.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116323"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142455","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":"Immunological mechanisms and immunotherapeutic strategies for the maternal-fetal interface diseases during pregnancy","authors":"Shuo Zheng ,&nbsp;Yulin Zhang ,&nbsp;Yi Xing ,&nbsp;Zhen Zhang ,&nbsp;Yaqing Zhang ,&nbsp;Liang Peng ,&nbsp;Suya Chen ,&nbsp;Yanli Zhang ,&nbsp;Longquan Shao","doi":"10.1016/j.intimp.2026.116260","DOIUrl":"10.1016/j.intimp.2026.116260","url":null,"abstract":"<div><div>The immune environment at the maternal-fetal interface is reliant on the precise regulation of various immune cells and their secreted cytokines, resulting in a coordinated balance of immune nutrition, immune defense, and immune tolerance to meet the needs of different stages of pregnancy. Disruption in the immunological microenvironment can lead to several pregnancy problems. In recent years, immunotherapy medications have made substantial advances in the treatment of maternal-fetal interface diseases during pregnancy. This paper provides a cellular and molecular review of the immunological mechanisms behind various common maternal-fetal interface diseases (preterm birth, recurring spontaneous abortion, preeclampsia, and fetal growth restriction). It offers a novel analysis of the mechanisms of action, application strategies, current research status, and future challenges for distinct immunotherapeutic agents from three separate perspectives: targeting different phases of inflammatory pathways, targeting particular immune cells at the maternal-fetal interface, and targeting specific autoantibodies associated with autoimmunity. The aim is to provide new insights for medication discovery, as well as precision diagnosis and treatment of pregnancy-related illnesses. These advancements will provide vital evidence for precision treatment of maternal-fetal interface diseases throughout pregnancy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116260"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146076141","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":"Exosomal MicroRNAs: From cellular communication to disease biomarkers","authors":"Reyhaneh Arefimehr ,&nbsp;Ajaz Ahmad","doi":"10.1016/j.intimp.2026.116328","DOIUrl":"10.1016/j.intimp.2026.116328","url":null,"abstract":"<div><div>Exosomes, extracellular vesicles secreted by various cell types, encapsulate specific microRNAs that play a critical role in biological processes, particularly intercellular communication. Exosomal microRNAs play a significant role in health and disease, as they regulate gene expression, modulate immune responses, and influence various signaling pathways. In healthy individuals, exosomal microRNAs contribute to homeostasis by facilitating tissue repair, regulating metabolic processes, and maintaining effective cellular communication. However, dysfunction in their activity may result in various health concerns, including cardiovascular disorders, neurological diseases, and cancer.</div><div>This review will explore biogenesis, mechanisms of action, and roles of exosomal microRNAs in health and disease. A comprehensive understanding of these biomarkers highlights their potential as diagnostic tools and therapeutic targets, thereby paving the way for innovative disease management strategies and the advancement of personalized medicine. Notably, most therapeutic applications of exosomal miRNAs remain at the preclinical or early translational stage, and further standardization and clinical validation are required before widespread implementation.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116328"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125013","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":"α-Methylene-γ-butyrolactone 3 inhibits the activation of NLRP3 inflammasome in sepsis by blocking both the priming and inflammasome assembly","authors":"Menghao Zeng ,&nbsp;Wei Xing ,&nbsp;Guibin Liang ,&nbsp;Fangfang Yuan ,&nbsp;Wenhua Wang ,&nbsp;Jie Liu ,&nbsp;Zhihui He","doi":"10.1016/j.intimp.2026.116305","DOIUrl":"10.1016/j.intimp.2026.116305","url":null,"abstract":"<div><div>Excessive NLRP3 inflammasome activation is implicated in pathologies like sepsis. While the histone acetyltransferase inhibitor α-methylene-γ-butyrolactone 3 (MB-3) is typically studied in cancer and epigenetic research, its anti-inflammatory potential remains largely unexplored. This study investigated the effect of MB-3 on NLRP3 inflammasome activation in both cellular and animal models. Results demonstrated that MB-3 treatment significantly downregulated NLRP3-associated inflammatory cytokines and proteins in vitro and in vivo. Mechanistic studies revealed that MB-3 acts by dual inhibition of the NLRP3 inflammasome. It disrupted the critical protein interactions between NLRP3-ASC and NLRP3-NEK7 and reduced ASC and NLRP3 oligomerization, thereby blocking the inflammasome assembly. Furthermore, MB-3 exhibited a protective effect on mitochondrial integrity by rescuing the loss of mitochondrial membrane potential and reducing the production of reactive oxygen species (ROS). In conclusion, these findings identify MB-3 as an effective inhibitor of the NLRP3 inflammasome, operating by blocking both the priming and assembly stages of activation. The results suggests that MB-3 is a promising potential therapeutic candidate for the treatment of NLRP3-driven inflammatory diseases.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116305"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105330","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}