International immunopharmacology最新文献

{"title":"Melittin alleviates osteoarthritis via mitophagy mediated by the AMPK/PINK1/Parkin Axis","authors":"Congcong Wu ,&nbsp;JianYuan Gao ,&nbsp;Chunhui Chen ,&nbsp;Zhiguang Zhang","doi":"10.1016/j.intimp.2026.116309","DOIUrl":"10.1016/j.intimp.2026.116309","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a common degenerative joint disease, mainly characterized by cartilage extracellular matrix (ECM) degradation, inflammatory response and chondrocyte apoptosis, with mitochondrial dysfunction as its key pathogenic factor. Melittin (Mel), the main active component of bee venom, has been confirmed to possess anti-inflammatory, antioxidant and anti-apoptotic effects, but its therapeutic effect and specific mechanism on OA have not been fully elucidated. This study explored the therapeutic effect and mechanism of Mel on OA through in vitro and in vivo experiments. In vitro experiments showed that Mel could dose-dependently reverse IL-1β-induced OA-like changes in rat chondrocytes: it not only upregulated ECM anabolic markers such as type II collagen (COL2) and aggrecan (ACAN), downregulated ECM catabolic markers such as matrix metalloproteinase-13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5), but also inhibited inflammatory markers such as IL-1β, IL-18, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), while restoring PINK1/Parkin-mediated mitophagy. Mechanistically, Mel exerted a protective effect against the pathological progression of OA induced by destabilization of the medial meniscus (DMM). In conclusion, Mel is expected to be a potential candidate for OA treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116309"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125035","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":"Autophagy-driven CCL7+ monocyte terminal differentiation program fuels CD8+ T cell–mediated cardiac injury in Sepsis","authors":"Xueyi Sun ,&nbsp;Shaolei Geng ,&nbsp;Zeyuan Wang ,&nbsp;Qingjiang Chen","doi":"10.1016/j.intimp.2026.116265","DOIUrl":"10.1016/j.intimp.2026.116265","url":null,"abstract":"<div><h3>Objective</h3><div>Sepsis-induced cardiomyopathy (SCM) is a life-threatening complication with poorly understood immune-metabolic drivers. This study aims to uncover the role of autophagy-dependent monocyte reprogramming and its contribution to myocardial injury via <em>CCL7</em>-mediated immune activation in sepsis.</div></div><div><h3>Methods</h3><div>We performed integrated analysis of bulk and single-cell transcriptomic data from septic patients (GSE65682, GSE152363, GSE167363). Autophagy activity and chemokine signaling were evaluated using bioinformatic approaches including WGCNA, pseudotime trajectory inference, and CellChat communication analysis. Functional validation was conducted through in vitro co-culture systems and in vivo models of LPS-induced sepsis, utilizing <em>CCL7</em> neutralization, flow cytometry, ELISA, and Western blot.</div></div><div><h3>Results</h3><div>Single-cell RNA sequencing revealed a distinct C6 monocyte subset characterized by high autophagic flux, elevated <em>CCL7</em> expression, and an M1-like inflammatory phenotype. Pseudotime analysis positioned C6 monocytes at the terminal end of monocyte differentiation, where they functioned as chemokine hubs amplifying cross-talk with CD8+ T cells, NK cells, and neutrophils. Mechanistically, <em>CCL7</em> secretion by C6 monocytes promoted autocrine M1 polarization and enhanced CD8+ T cell activation via <em>CCR1/CCR2</em>-dependent <em>PI3K-AKT</em> signaling. In co-culture, <em>CCL7</em>-stimulated CD8+ T cells induced oxidative stress, cytokine release, and cardiomyocyte apoptosis. In vivo, <em>CCL7</em> neutralization alleviated myocardial injury, reduced cardiac ROS accumulation, and suppressed systemic inflammation.</div></div><div><h3>Conclusions</h3><div>Our findings identify a pathogenic autophagy-<em>CCL7</em>-monocyte-T cell axis as a central driver of immuno-metabolic dysregulation in SCM. Targeting <em>CCL7</em>-mediated signaling may represent a novel immunomodulatory strategy to restore cardiac immune homeostasis and mitigate sepsis-induced myocardial injury.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116265"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104963","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 novel SPPARM YR3–16 ameliorates metabolic disorders in vivo and attenuates adipocyte inflammation in vitro via PPARγ-dependent ERK suppression","authors":"Cunyu Feng ,&nbsp;Quan Liu ,&nbsp;Jun Peng ,&nbsp;Chunming Jia ,&nbsp;Xuan Pan ,&nbsp;Shuainan Liu ,&nbsp;Xiaohui Geng ,&nbsp;Jiayu Zhai ,&nbsp;Min Wu ,&nbsp;Siming Hao ,&nbsp;Liran Lei ,&nbsp;Kejia Xu ,&nbsp;Yuting Ma ,&nbsp;Lei Lei ,&nbsp;Zhanzhu Liu ,&nbsp;Yi Huan ,&nbsp;Zhufang Shen","doi":"10.1016/j.intimp.2026.116320","DOIUrl":"10.1016/j.intimp.2026.116320","url":null,"abstract":"<div><div>Obesity-related metabolic disorders and adipocyte inflammation are key drivers of type 2 diabetes, but conventional therapies remain suboptimal in addressing these core pathologies. This study aimed to characterize YR3–16 as a novel selective peroxisome proliferator-activated receptor γ modulator (SPPARM) with efficacy in improving metabolic homeostasis and reducing adipocyte inflammation.</div><div>YR3–16 is a novel tetrahydroisoquinoline derivative that selectively activates PPARγ and exhibits a binding mode distinct from that of pioglitazone.</div><div>In spontaneous obese and type 2 diabetic KKAy mice, oral administration of YR3–16 (three doses, 25/50/75 mg/kg) for 30 days dose-dependently ameliorated metabolic disorders: it improved insulin sensitivity (insulin tolerance test), and reduced plasma triglycerides, free fatty acids and total cholesterol. Consistent results were also observed in diet-induced obese (DIO) mice. In 3 T3-L1 adipocytes, YR3–16 (10 μM) reprogrammed lipid metabolism at the gene transcriptional level, and suppressed pro-inflammatory cytokine secretion (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)), associated with the inhibition of extracellular signal-regulated kinase (ERK) signaling pathway, which was abolished by the peroxisome proliferator-activated receptor γ antagonist GW9662.</div><div>YR3–16, as a novel SPPARM, concurrently improves metabolic disorders in vivo and attenuates adipocyte inflammation via peroxisome proliferator-activated receptor γ activation, highlighting its potential for treating obesity-related diseases.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116320"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149773","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":"Mushroom-derived Immunomodulators: Mechanistic insights, omics integration, AI innovation, and clinical applications in precision immunotherapy","authors":"Hua Zhang ,&nbsp;Beng Fye Lau ,&nbsp;Chin Siang Kue","doi":"10.1016/j.intimp.2026.116283","DOIUrl":"10.1016/j.intimp.2026.116283","url":null,"abstract":"<div><div>Mushrooms are rich in structurally diverse bioactive compounds that exert potent immunomodulatory effects, making them promising candidates for next-generation immunotherapies. This review comprehensively examines their immunomodulatory mechanisms, emphasizing roles in both innate and adaptive immune regulation. Specifically, it explores the interactions of polysaccharides, fungal immunomodulatory proteins (FIPs), lectins, terpenoids, and phenolics with pattern recognition receptors (PRRs) on immune cells such as macrophages, dendritic cells, and natural killer cells, which subsequently trigger downstream signaling cascades that modulate cytokine production, regulate Th1/Th2 balance, and promote regulatory T cell function. By influencing these immune pathways, mushroom-derived compounds have shown significant therapeutic potential in cancer immunotherapy, infectious disease management, autoimmune modulation, and functional nutrition. Building on these findings, this review further discusses how recent advances in omics technologies and artificial intelligence (AI) could unlock deeper insights into the biosynthetic pathways, immune targets, and therapeutic mechanisms of these compounds, as well as how such tools might be harnessed to predict and optimize immunomodulatory efficacy. To address key challenges such as variability in extract composition, lack of standardized analytical methods, and limited clinical validation, this review proposes integrative strategies including the implementation of standardized extraction protocols, AI-assisted compound profiling, and omics-guided bioinformatics modeling. Collectively, these approaches aim to bridge the gap between experimental discovery and clinical translation, positioning mushrooms as precision-guided agents in next-generation immunotherapy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116283"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146076139","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":"Chondrocyte inflammatory-immune responses in osteoarthritis: From pathogenesis to therapeutic intervention","authors":"Yizhuo Deng ,&nbsp;Jia Liu ,&nbsp;Abdulaziz S. Bamahel ,&nbsp;Pinhan Zhang ,&nbsp;Aining Yu ,&nbsp;Hongyun Cui ,&nbsp;Hui Xu ,&nbsp;Yuli Fang","doi":"10.1016/j.intimp.2026.116270","DOIUrl":"10.1016/j.intimp.2026.116270","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a chronic disease characterized by cartilage degeneration, and recent evidence has demonstrated its close association with inflammatory and immune responses. Current research on OA has predominantly focused on biomechanical injury, cartilage matrix degradation, and subchondral bone remodeling, with the underlying molecular mechanisms partially elucidated. However, the role of inflammatory–immune responses in OA pathogenesis, particularly the pathological functions of chondrocytes within the inflammatory micro-environment and their associated immune signaling pathways, remains inadequately elucidated.This review systematically summarizes the pivotal roles of chondrocytes in the inflammatory–immune mechanisms of OA, highlighting how inflammatory and immune mediators within chondrocytes contribute to structural and functional damage to joint tissues, as well as their involvement in regulating inflammatory cascades, metabolic reprogramming, cellular senescence, and programmed cell death through canonical signaling pathways. Moreover, we emphasize the critical roles of chondrocytes in initiating, sustaining, and amplifying the inflammatory micro-environment of OA, and discuss their potential as therapeutic targets. Collectively, this review aims to provide a theoretical framework for mechanistic studies and the development of precision therapeutic strategies in OA.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116270"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146076161","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 “Unravelling the role of Interleukin-12 in Neuroinflammatory mechanisms: Pathogenic pathways linking Neuroinflammation to neuropsychiatric disorders” [Int. Immunopharmacol. 156 (2025) 114654]","authors":"Rupali Chauhan,&nbsp;Maneesh Mohan,&nbsp;Ashi Mannan,&nbsp;Sushma Devi,&nbsp;Thakur Gurjeet Singh","doi":"10.1016/j.intimp.2026.116239","DOIUrl":"10.1016/j.intimp.2026.116239","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116239"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092849","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":"Agmatine ameliorates poly(I:C)-induced lung injury through IL-10/STAT3-dependent reprogramming of macrophage inflammatory responses","authors":"Zhen Sun ,&nbsp;Xiaochang Zhang ,&nbsp;Sha Liao ,&nbsp;Zhe Zhou","doi":"10.1016/j.intimp.2026.116247","DOIUrl":"10.1016/j.intimp.2026.116247","url":null,"abstract":"<div><div>The emerging field of immunometabolism posits that endogenous metabolites are pivotal regulators of immune responses, yet their therapeutic exploitation remains nascent. Investigating this paradigm in lung injury, we observed that agmatine, a decarboxylation product of L-arginine, was significantly depleted in poly(I:C)-induced murine lung injury and in a clinical cohort characterized by virus-associated pulmonary involvement, suggesting a potential association with lung pathology. In mice, exogenous agmatine supplementation ameliorated lung pathology and weight loss, effects that were contingent upon reprogramming of macrophage inflammatory responses. Mechanistically, agmatine exerts its anti-inflammatory effects through macrophage-specific mechanisms: it selectively inhibits macrophage-derived TNF-α and CXCL10 without affecting the NF-κB signaling pathway. Transcriptomic analysis of murine macrophages revealed that agmatine significantly upregulates IL-10 expression, and its protective effects were reversed using either IL-10R neutralizing antibody or macrophages from IL-10-deficient mice. In murine macrophages, further investigation confirmed that agmatine promotes STAT3 phosphorylation and nuclear translocation, while STAT3 knockdown partially abrogated its anti-inflammatory efficacy. Our findings position agmatine within the expanding realm of immunometabolic therapy, highlighting its potential as a therapeutic strategy for lung injury by harnessing an endogenous anti-inflammatory circuit.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116247"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037431","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":"Comment on “Fennel essential oil and its nanoemulsion modulate macrophage-mediated inflammatory responses and promote pressure ulcer healing”","authors":"Dharmendra Singh Rajput ,&nbsp;Mitul Bhoi ,&nbsp;Shubham Singh","doi":"10.1016/j.intimp.2026.116184","DOIUrl":"10.1016/j.intimp.2026.116184","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116184"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037433","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":"Comment on: Asprosin mediates diabetes-associated depression via provoking the cascade of pyroptosis-neuroinflammation-kynurenine pathway disorder in the hippocampus","authors":"Li Jiamei ,&nbsp;Li Keda","doi":"10.1016/j.intimp.2026.116266","DOIUrl":"10.1016/j.intimp.2026.116266","url":null,"abstract":"<div><div>This letter to the editor comments on the study by Jiang et al. investigating the role of Asprosin in diabetes-associated depression. We acknowledge the novel finding that Asprosin mediates hippocampal dysfunction by triggering a cascade of “pyroptosis–neuroinflammation–kynurenine pathway” disruption. We further highlight several avenues for deeper exploration, including the brain-region specificity of Asprosin action, the specific cell types undergoing pyroptosis, and the direct mechanistic links within this pathway. Further investigation into these aspects may help translate this discovery into targeted therapeutic strategies.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116266"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146076254","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":"Exogenous dendritic cell-derived exosomes promote Treg differentiation via IDO1-Kyn-AhR axis and improve cardiac function after myocardial infarction","authors":"Yiran Qin ,&nbsp;Youming Zhang ,&nbsp;Mingxuan Li ,&nbsp;Di Ding ,&nbsp;Rong Luo ,&nbsp;Haibo Liu","doi":"10.1016/j.intimp.2026.116253","DOIUrl":"10.1016/j.intimp.2026.116253","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) play a vital role in cardiac remodeling after myocardial infarction (MI). Our previous study demonstrated that dendritic cell-derived exosomes (DEXs) improve cardiac function after MI by promoting Treg differentiation. However, the underlying mechanisms remain incompletely understood. In this study, we found that necrotic HL-1 cardiomyocyte supernatant-conditioned DEXs (MI-DEXs) expressed high level of indoleamine 2,3-dioxygenase 1 (IDO1), which led to increased kynurenine (Kyn) production and subsequently upregulation of aryl hydrocarbon receptor (AhR) in CD4⁺ T cells. Overexpression of IDO1 in MI-DEXs enhanced Treg differentiation and further improved cardiac function after MI, whereas knockdown of IDO1 attenuated these effects. In addition, pharmacological inhibition of AhR abolished the enhanced Treg differentiation and functional benefits induced by IDO1-overexpressing MI-DEXs, both in vitro and in vivo. Collectively, our findings reveal a novel mechanism by which MI-DEXs promote Treg differentiation via the IDO1-Kyn-AhR axis, and suggest that administration of MI-DEXs could be a potential intervention to facilitate cardiac repair after MI.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"173 ","pages":"Article 116253"},"PeriodicalIF":4.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037435","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}