Inflammation最新文献

{"title":"MAPK15 Attenuates Intestinal Epithelial Cell Senescence-Like Phenotype to Regulate Gut Homeostasis and Inflammation by Phosphorylating Suz12 to Suppress Drp1-Mediated Mitochondrial Fission Damage.","authors":"Juan Li, Gang Chen, Xinyi Bao","doi":"10.1007/s10753-026-02514-6","DOIUrl":"10.1007/s10753-026-02514-6","url":null,"abstract":"<p><p>The senescence of intestinal epithelial cells (IECs) is closely associated with the development of ulcerative colitis (UC), but the underlying regulatory mechanism remains unclear. Although mitogen activated protein kinase 15 (MAPK15) has been shown to inhibit cellular senescence, its specific role in UC has not yet been clarified. This study investigates the role of MAPK15 in modulating IEC senescence during UC and explores the molecular mechanisms involved in this regulatory process. The senescence phenotype and MAPK15 expression in colon tissues from UC patients, dextran sodium sulfate (DSS)-induced UC mice, and DSS-induced NCM460 cells were detected by SA-β-Gal staining, immunohistochemistry (IHC) staining, and Western blot analysis. To further determine the molecular mechanism of the MAPK15/Suz12/Drp1 axis in UC, MAPK15 was overexpressed and Suz12 was silenced, and the underlying regulatory interactions were assessed using techniques including Co-immunoprecipitation (Co-IP), RIP-qPCR, and RNA pull-down. The results showed that the expressions of senescence-associated markers (p53, p16, and p21) and senescence-associated secretory phenotype (SASP) factors (IL-6, IL-8, and MMP-3) in IECs from UC patients and DSS-induced mice were upregulated, whereas the expression of MAPK15 was downregulated. Functional experiments further demonstrated that overexpression of MAPK15 alleviated DSS-induced intestinal inflammation, reduced cellular senescence-like phenotype, and suppressed Drp1-dependent mitochondrial fission. Mechanistically, MAPK15 enhanced the binding of Suz12 to Drp1 mRNA through phosphorylation of Suz12, which reduced the stability of Drp1 mRNA, and thereby inhibited Drp1-mediated mitochondrial fission damage. However, silencing of Suz12 reversed the protective effect induced by MAPK15 overexpression. In conclusion, these findings indicated that MAPK15 contributed to the inhibition of mitochondrial fission through regulation of the Suz12/Drp1 axis, thereby mitigating IEC senescence-like phenotype and suppressing the progression of UC. These results suggested that MAPK15 might serve as a potential therapeutic target for UC.Clinical Trial Number: Not applicable.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13243336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dendritic Cells Derived MMP9 Fuels Sepsis-Induced Cardiac Dysfunction Through JNK/AP1 Driven Pro-Inflammatory Cytokine and Nitric Oxide Storm.","authors":"Jiewen Deng, Yulan Qu, Yanyan Jiang, Yao Xie, Xiaotian Ma, Jian Shen, Zhenhong Guo, Meixiang Xiang","doi":"10.1007/s10753-025-02374-6","DOIUrl":"10.1007/s10753-025-02374-6","url":null,"abstract":"<p><p>Metalloproteinase9 is an important inflammatory mediator, but its contribution to sepsis-induced myocardial dysfunction (SIMD) remains unclear. In this study, we found that MMP9 deletion in mice evoked resistance to LPS-triggered septic cardiac dysfunction and lethality, accompanied by heavily reduced serum level of inflammatory factors and the myocardial damage markers. Similar results were acquired when an MMP9 inhibitor was used to treat LPS-induced sepsis, indicating that MMP9 promoted the progression of SIMD. It is well-known that DCs can induce inflammatory response to promote septic tissue damage. Notably, MMP9-/- BMDCs were significantly more effective in reducing sepsis-induced myocardial dysfunction compared to WT BMDCs. Mechanistically, MMP9 deficiency in BMDCs mainly curtailed the release of IL-6, IL-1β, IL-17 A, and nitric oxide via the JNK/AP1 pathway, thus safeguarding cardiomyocytes from death. Collectively, this study contributed new insights into the role of MMP9 in DCs within the context of SIMD.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13233659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dock2 Protects Colitis by Facilitating Akkermansia Colonization via Suppressing IL-22-Reg3 Activity.","authors":"Min Lu, Shaoting Xu, Ying Tan, Jianping Deng, Bingbing Feng, Ding Qiu, Xinying Wang, Haiyang Sun, Kaile Ji, Bowen Zhu, Shixian Hu, Xueting Wu, Minhu Chen, Yoichiro Iwakura, Xinying Wang, Rui Feng, Yangfan Qi, Ce Tang","doi":"10.1007/s10753-026-02511-9","DOIUrl":"10.1007/s10753-026-02511-9","url":null,"abstract":"<p><p>Dedicator of cytokinesis 2 (DOCK2) is a guanine nucleotide exchange factor upregulated in patients with inflammatory bowel disease (IBD), yet its role in intestinal homeostasis remains obscure. Here, we show that both systemic and T cell–specific Dock2-deficient mice develop exacerbated chemical-induced colitis, characterized by reduced CD8⁺ T cells and impaired IFN-γ production, alongside elevated IL-22 and Reg3γ/β antimicrobial peptides (AMPs), and accompanied with decreased colonization of Akkermansia (A.) muciniphila, a beneficial Verrucomicrobia species. Reg3γ/β expression was diminished in IL-22– and RORγt–deficient mice, and both AMPs inhibited A. muciniphila growth. Co-housing with wild-type mice or A. muciniphila reconstitution rescued colitis severity in Dock2-deficient mice. Pharmacologic inhibition of Dock2-Rac1 signaling suppressed IFN-γ in murine and human T cells. Mechanistically, IFN-γ restricted IL-22 by enhancing H3K27 trimethylation on Ahr promoter and suppressing AHR transcription. These findings identify a Dock2–IFN-γ–IL-22–Reg3 axis that controls commensal microbiota and colitis. Targeting Dock2 signaling may offer new therapeutic opportunities in IBD.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13236751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose-Derived Proinflammatory Visfatin Promotes Vascular Calcification via TLR4 and is Suppressed by Empagliflozin.","authors":"Yue Zhang, Yarui Zhao, Yijie Luo, Lei Wang, Jing Liao, Huixia Lu, Xinyu Zhang, Xiaoping Ji","doi":"10.1007/s10753-026-02507-5","DOIUrl":"10.1007/s10753-026-02507-5","url":null,"abstract":"<p><p>Vascular calcification, a common complication of metabolic diseases such as diabetes and obesity, is closely associated with chronic inflammation and contributes to cardiovascular morbidity. The adipokine visfatin, which is secreted by visceral fat, is a proinflammatory mediator linked to metabolic dysfunction. In this study, we investigated its role in vascular calcification. A murine model was established by vitamin D injection. Serum visfatin levels were significantly elevated in patients with higher coronary artery calcification scores and in calcified mice, accompanied by increased visfatin expression in visceral fat. Adipose tissue-specific overexpression of visfatin further exacerbated vitamin D-induced vascular calcification. In cultured vascular smooth muscle cells (VSMCs), visfatin increased osteogenic differentiation under calcification conditions. Mechanistically, visfatin directly bound to TLR4 to promote osteogenic transformation of VSMCs, whereas TLR4 knockout markedly attenuated visfatin- and calcification medium-induced aortic calcification both in vivo and in vitro. Furthermore, the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin alleviated vascular calcification and reduced serum visfatin levels in mice. Mechanistically, empagliflozin suppressed p38/NF-κB activation, inhibited NF-κB nuclear translocation, and reduced NF-κB binding to the visfatin promoter, thereby decreasing visfatin expression in adipocytes. Collectively, these findings identify visfatin as a proinflammatory adipose-derived regulator of vascular calcification via TLR4 and a potential therapeutic target for vascular calcification and related cardiovascular disorders.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13236799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dual Role of Interleukin-10 in Sepsis: Research Progress and Therapeutic Prospects.","authors":"Xianwen Wang, Qihang Huang, Jinwei Dai, Lina Zhang, Zhaoxin Qian","doi":"10.1007/s10753-026-02512-8","DOIUrl":"10.1007/s10753-026-02512-8","url":null,"abstract":"<p><p>Sepsis is life-threatening organ dysfunction caused by a dysregulated host response in which hyperinflammation and counter-regulatory immunosuppression often coexist and shift over time. Interleukin-10 (IL-10) is a central immunoregulatory cytokine in this balance. Early IL-10 signaling can restrain innate cytokine amplification, limit tissue injury, and promote tolerance; however, sustained or context-mismatched IL-10 impairs antigen presentation and antimicrobial effector functions, contributing to sepsis-associated immunoparalysis, secondary infections, and poor outcomes. We summarize the cellular sources and multilayer regulation of IL-10 in sepsis, spanning transcriptional programs, cytokine circuits, and immunometabolic remodeling. Clinically, IL-10 is rarely informative as a standalone biomarker; its utility increases when interpreted longitudinally and integrated with immune-function readouts (e.g., lymphocyte indices, monocyte HLA-DR) and broader biomarker patterns to assign host-response endotypes. We then review IL-10–linked therapeutic strategies and propose an IL-10-aware precision framework that connects biomarker trajectories to endotype-aligned treatment windows, safety guardrails, and adaptive trial designs. Integrating mechanistic insight with dynamic stratification may enable more effective, individualized host-directed interventions in sepsis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13236793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AQP1 is Involved in NLRP3-Related Microglial Polarization and Cognitive Impairment in Chronic Sleep Deprivation.","authors":"Yanhong Xiong, Weidong Liang, Hong Zhu, Xilong Guan, Pengcheng Yi, Lieliang Zhang, Yueyang You, Yingchuan Hu, Xiuqin Rao, Jun Ying, Xifeng Wang, Fuzhou Hua","doi":"10.1007/s10753-026-02498-3","DOIUrl":"10.1007/s10753-026-02498-3","url":null,"abstract":"<p><p>Sleep deprivation is closely associated with neuroinflammation and cognitive dysfunction, yet its underlying molecular mechanisms remain incompletely understood. Aquaporin-1 (AQP1) has been implicated in microglial regulation, but its role in chronic sleep deprivation (CSD)–induced cognitive impairment remains unclear. A chronic sleep deprivation (CSD) mouse model and an in vitro BV2 microglial inflammation model were established. Learning and memory functions were assessed using the Y-maze, novel object recognition, and Morris water maze tests. Transcriptomic sequencing was performed to identify key regulatory genes. AQP1 expression, NLRP3 inflammasome–related responses, microglial polarization, hippocampal pathology, and neuroinflammatory responses were systematically evaluated using molecular, histological, and immunological approaches. In addition, high-throughput virtual screening and molecular dynamics simulations were employed to analyze the potential association between curcumin and AQP1. CSD induced significant impairments in learning and memory, accompanied by hippocampal neuronal injury and neuroinflammatory activation. Transcriptomic analysis revealed that AQP1 was markedly upregulated in the hippocampus of CSD mice and was predominantly localized in microglia. AQP1 knockdown significantly ameliorated CSD-induced cognitive deficits and neuronal damage was accompanied by reduced NLRP3 inflammasome–related readouts, and promoted microglial polarization toward the M2 phenotype, these effects were largely reversed by the NLRP3 agonist nigericin. Furthermore, curcumin attenuated microglial M1 polarization, reduced neuroinflammation, and improved cognitive performance, alongside changes in AQP1 expression and inflammasome-related measures. AQP1 is associated with CSD-related cognitive impairment and neuroinflammatory responses, accompanied by changes in microglial polarization and NLRP3 inflammasome–related signaling. Curcumin shows neuroprotective effects under CSD conditions; whether AQP1 is a direct molecular target requires further validation.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13222902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Transcriptomics Identifies a Pivotal Role of SPHK1⁺ Macrophage-Driven Inflammation in Mechanism of Aortic Dissection and Highlights SPHK1 as a Therapeutic Target.","authors":"Dianjun Tang, Yanshuo Han, Han Jiang, Jamol Uzokov, Fandong Li, Zhong Wang, Mario D'Oria, Philipp Erhart, Dittmar Boeckler, Yu Lun, Jian Zhang","doi":"10.1007/s10753-026-02505-7","DOIUrl":"10.1007/s10753-026-02505-7","url":null,"abstract":"<p><p>Macrophages are a key heterogeneous cell population involved in the pathogenesis and progression of acute aortic dissection (AD), though their mechanisms remain unclear. This study aims to identify the gene driving inflammatory damage in acute AD within a specific macrophage subcluster, highlighting potential therapeutic targets. Single-cell RNA sequencing (scRNA-seq) was employed to analyze the cellular heterogeneity in acute AD and normal aortic tissues. Bioinformatic analysis was conducted to identify the key gene. The role of sphingosine kinase 1 (SPHK1) was further explored using human acute AD tissue samples, macrophage cell line experiments, and AD mouse models. scRNA-seq identified six macrophage subclusters in AD tissues, with subcluster a exhibiting a pronounced pro-inflammatory phenotype. SPHK1 was significantly upregulated in this subcluster and was identified as the key regulatory gene. In vitro, inhibition of SPHK1 reduced macrophage-mediated inflammatory damage via the S1P-S1PR2/3-RhoA-ROCK1 signaling pathway. In vivo studies revealed a 40% reduction in the incidence of AD and significantly reduced severity in mice treated with PF-543 (a specific SPHK1 inhibitor). In this model, PF-543 reduced macrophage infiltration and the inflammatory damage caused by inflammatory factors and matrix metalloproteinases. This study identifies macrophage-driven inflammation, particularly via SPHK1, as a central mechanism in AD. Targeting SPHK1 and the associated S1P-S1PR2/3-RhoA-ROCK1 signaling pathway offers a potential therapeutic strategy for mitigating AD progression.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Hydroxybutyrate Attenuates Diabetic Kidney Disease Partially Via β-hydroxybutyrylation of Nrf2.","authors":"Tingting Zhou, Linlin Huang, Yanqiu He, Xi Cheng, Qian Ren, Cheng Zeng, Qiming Gong, Yanqun Li, Linqiang Ma, Zongze Jiang, Yang Long, Qin Wan, Yong Xu, Wei Huang","doi":"10.1007/s10753-025-02366-6","DOIUrl":"10.1007/s10753-025-02366-6","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is one of the predominant microvascular complications in diabetes. In recent years, the nuclear factor E2-related factor 2 (Nrf2)-mediated anti-oxidative stress pathway is tightly regulated by multiple post-translational modifications, governing its role in countering oxidative stress and DKD pathogenesis. Recent studies have found that the principal constituent of ketone bodies, β-hydroxybutyrate (β-HB), not only serves as an alternative energy source, but also induced lysine β-hydroxybutyrylation (Kbhb), which has various unknown pathophysiological functions. Previous research reports that β-HB activates Nrf2 and then treats DKD, yet its underlying molecular mechanism remains unclear. To explore the mechanism of β-HB induced Kbhb in DKD, β-HB was administered in both in vivo and in vitro. Our results verified that exogenous β-HB supplementation alleviated dysglycolipidemia, inhibited proteinuria and renal dysfunction. Meanwhile, β-HB enhanced Nrf2 Kbhb modification, and activated the Nrf2 signaling to mitigate renal inflammatory-fibrotic injury in diabetes. However, inhibition of Kbhb partially reversed β-HB-mediated Nrf2 activation and nephroprotection. In conclusion, our data reveal that β-HB attenuates DKD, β-HB-induced Nrf2 Kbhb modification may be an important molecular mechanism in the pathogenesis and treatment of DKD.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13234043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147672768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6-Hydroxyflavone Attenuates Inflammatory Osteolysis by Inhibiting Osteoclast Activation via the Nrf2 and Calcium Signaling Pathways.","authors":"Kun Qian, Qizhen Lu, Weiyi Wang, Qige Lu, Shenghong Dai, Chuanyun Fu, Shui Sun","doi":"10.1007/s10753-026-02500-y","DOIUrl":"10.1007/s10753-026-02500-y","url":null,"abstract":"<p><p>Inflammatory osteolysis (IO) is a pathological bone disorder characterized by excessive osteoclast activation and bone resorption driven by inflammatory mediators and oxidative stress. 6-Hydroxyflavone (6-HOF), a natural flavonoid with potent antioxidant and anti-inflammatory properties, has not been fully investigated in the context of IO. In this study, we explored the therapeutic effects and underlying mechanisms of 6-HOF in LPS-induced osteoclastogenesis and inflammatory bone loss. Network pharmacology analysis predicted that 6-HOF primarily targets oxidative stress and calcium signaling pathways. In vitro, 6-HOF inhibited multinucleated osteoclast formation in a concentration-dependent manner without affecting cell viability, downregulated osteoclast-specific genes including Nfatc1, Ctsk, Dc-stamp, and Mmp9, and significantly reduced the expression and secretion of pro-inflammatory cytokines IL-6, TNF-α, and IL-1β. Mechanistically, 6-HOF suppressed intracellular ROS accumulation, disrupted RANKL-induced Ca²⁺ oscillations, and inhibited NFATc1 signaling essential for osteoclast differentiation, while activating the Keap1/Nrf2 antioxidant pathway to restore redox homeostasis. In vivo, micro-CT analyses showed that 6-HOF treatment alleviated LPS-induced bone loss by reducing osteoclast numbers and preserving trabecular microarchitecture. Collectively, these results indicate that 6-HOF inhibits osteoclastogenesis and inflammatory responses through the dual regulation of oxidative stress, calcium signaling, and pro-inflammatory cytokine production, highlighting its potential as a promising therapeutic candidate for IO and other bone-destructive disorders.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13183763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFN-I Induces Keratinocytes Necroptosis via ZBP1-MLKL Axis in Oral Lichen Planus.","authors":"Xinke Jiang, Junjun Chen, Yilin Yao, Yirao Lai, Xiaojie Yang, Guoyao Tang, Lei Sun, Yufeng Wang","doi":"10.1007/s10753-026-02497-4","DOIUrl":"10.1007/s10753-026-02497-4","url":null,"abstract":"<p><p>Oral lichen planus (OLP) is a prevalent chronic inflammatory condition that affects the oral mucosa. Histologically, it is characterized by the liquefaction and degeneration of basal epithelial cells, indicating a disruption of the basal layer architecture, which may represent an early event in the disease’s pathogenesis. However, the molecular mechanisms underlying this epithelial damage remain poorly understood. In our study, histological staining and transmission electron microscopy revealed aberrant cell death in the basal epithelial layer of OLP tissues. Immunodetection demonstrated the presence of phosphorylated mixed lineage kinase domain-like protein (pMLKL), a key marker of necroptosis, specifically localized to basal keratinocytes. Notably, interferon type I (IFN-I), particularly IFNα, was significantly upregulated in OLP mucosa compared to healthy controls. The expression of Z-DNA binding protein 1 (ZBP1), an IFN-stimulated gene and an upstream regulator of necroptosis, was elevated in pMLKL-positive epithelial cells. In vitro stimulation with IFNα2a induced the expression of ZBP1 and pMLKL in HaCaT keratinocytes, while ZBP1 knockdown abrogated MLKL phosphorylation. Collectively, these results suggest that, in the context of increased IFN-I signaling, ZBP1 is aberrantly upregulated in the OLP epithelium, promoting necroptosis in basal keratinocytes. This necroptotic activity may contribute to the damage and disruption of the basal layer, providing novel insights into the pathogenesis of OLP and highlighting potential molecular targets for therapeutic intervention.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13171736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}