Inflammation最新文献

{"title":"Long Non-coding RNA TLX1NB Regulates Inflammatory Response in Periodontitis by Interacting With Matrix Metalloproteinase 8.","authors":"Shouxiang Yang, Wanting Yuan, Ziqiong Yang, Jiaxuan He, Xiaoqian Wang, Lei Lu, Zhijia Xu, Xiaoyu Yao, Chunai Zhan, Long Mei, Wanyu Zhang, Wei Shao, Xiaoyu Sun","doi":"10.1007/s10753-026-02541-3","DOIUrl":"10.1007/s10753-026-02541-3","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) play critical roles in regulating inflammatory responses in periodontitis. This investigation focused on the involvement of the lncRNA T cell leukemia homeobox 1 neighbor (TLX1NB) in periodontitis and its regulatory role in modulating matrix metalloproteinase 8 (MMP8). Transcriptome sequencing and RT-qPCR validation revealed a significant upregulation of TLX1NB in gingival tissues from patients with periodontitis. This upregulation was recapitulated in an in vitro inflammatory model using TNF-α-stimulated human gingival fibroblasts (HGFs). Both FISH and cellular fractionation assays demonstrated that TLX1NB is predominantly enriched in the nucleus of HGFs. Functionally, TLX1NB knockdown attenuated the production of key pro-inflammatory cytokines, including IL-1β, IL-6, and IL-8, in TNF-α-stimulated HGFs, while concurrently enhancing cell proliferation. Mechanistically, RNA pull‑down and RIP assays confirmed a direct molecular interaction between TLX1NB and MMP8, suggesting that TLX1NB may regulate MMP8 function through direct binding. Functional analysis further demonstrated that TLX1NB and MMP8 act cooperatively to regulate inflammatory responses and apoptosis in HGFs. Ultimately, our results show that reducing TLX1NB expression alleviates periodontitis-associated inflammation and cellular dysfunction. This effect is associated with MMP8 and correlates with decreased NF-κB signaling. Collectively, these findings highlight TLX1NB as a promising therapeutic target for the treatment of periodontal disease.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283417","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":"Fusobacterium varium Exacerbates Neutrophil-driven Intestinal Inflammation Associated with Succinate-SUCNR1-NF-κB Signaling.","authors":"Qian Wang, Han Xiao, Wenxiu Liu, Xiangji Dang, Yanrui Bai, Ruihong Xiao, Liyu Tong, Yan Wang, Mi Li, Shuhan Wang, Sugui Pu, Duoji Pei, Dekui Zhang, Xiang Wang, Guang Hu, Jingjing Guo, Xiaojie Jin, Long Qin, Chunjiang Zhang, Yana Li, Tiansheng Zhang, Jing Yang, Qi Wang, Hui Sun","doi":"10.1007/s10753-026-02547-x","DOIUrl":"10.1007/s10753-026-02547-x","url":null,"abstract":"<p><p>Disruption of gut microbial homeostasis is a hallmark of ulcerative colitis (UC), yet the specific pathobionts and effector molecules driving mucosal inflammation remain unclear. In this study, metagenomic sequencing of fecal samples from 37 patients with UC and 30 healthy controls was performed to identify differentially enriched bacterial species. Fusobacterium varium (F. varium) was found to be significantly enriched in patients with UC and was therefore selected for further functional investigation. Germ-free mice colonized with F. varium developed more severe dextran sulfate sodium (DSS)-induced colitis, accompanied by enhanced mucosal inflammation. In addition, F. varium culture supernatants increased NF-κB reporter activity and inflammatory signaling at the protein level. Bioactivity-guided fractionation combined with mass spectrometry identified succinate as a major candidate bacterial-derived bioactive metabolite. Succinate exacerbated colonic inflammation in vivo and promoted neutrophil recruitment, whereas inhibition of CXCR2 signaling reduced neutrophil infiltration and alleviated disease severity. In vitro experiments further demonstrated that succinate activated NF-κB signaling in HL-60-derived neutrophils through succinate receptor 1 (SUCNR1) and induced the production of inflammatory mediators, including CXCL8. Collectively, these findings support a role for F. varium in exacerbating intestinal inflammation under colitic conditions, at least in part through succinate-associated neutrophil recruitment.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277418","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":"Downregulation of Lonp1 Promotes Melanocyte Pyroptosis via Suppressing Mitophagy and Activating NLRP3 Pathway in Vitiligo under Oxidative Stress.","authors":"Xin Huang, Tianqi Wei, Youming Guo, Jing Zhu, Lingling Luo, Zhaokang Zhou, Baiyi Zuo, Guanying Liu, Beilei Xu, Chengrang Li","doi":"10.1007/s10753-026-02538-y","DOIUrl":"10.1007/s10753-026-02538-y","url":null,"abstract":"<p><p>Vitiligo is an autoimmune skin disease characterized by the loss of epidermal melanocytes. Oxidative stress serves as a key initiating factor in its pathogenesis. Mitochondria, known as the powerhouse of the cell, perform multiple essential functions in eukaryotic cells and participate in melanocyte physiological processes. Lonp1 is a crucial mitochondrial matrix soluble protease involved in maintaining mtDNA stability, clearing aberrant proteins, and regulating mitochondrial homeostasis. Meanwhile, mitophagy serves as a crucial function within the mitochondrial quality control system, responsible for eliminating damaged mitochondria. Pyroptosis is a form of programmed cell death mediated by inflammasomes, accompanied by cell membrane pore formation and the release of inflammatory cytokines. This study confirmed that oxidative stress was associated with decreased Lonp1 in PIG1 cells, the human melanocyte line. This downregulation impairs mitochondrial homeostasis by suppressing the expression of PINK1, a key mitophagy-related protein, ultimately leading to activation of the NLRP3 inflammasome pathway, release of IL-1β, and induction of melanocyte pyroptosis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271330","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":"When the Liver Flares: Inflammatory and Immunometabolic Mechanisms Driving the Transition from MASLD to MASH.","authors":"Cristina Vecchio, Anteneh Nigussie Sheferaw, Emmanuel Kivumbi, Ian Stoppa, Deepika Pantham, Foteini Christaki, Alessia Provera, Umberto Dianzani, Salvatore Sutti","doi":"10.1007/s10753-026-02545-z","DOIUrl":"10.1007/s10753-026-02545-z","url":null,"abstract":"<p><p>The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is steadily increasing worldwide, primarily due to the ongoing obesity pandemic. Although MASLD may initially present as a relatively benign condition, it has the potential to progress to metabolic dysfunction-associated steatohepatitis (MASH), a more severe form that can lead to cirrhosis and hepatocellular carcinoma (HCC). A variety of factors contribute to the pathogenesis of MASLD, including gut dysbiosis, insulin resistance, dyslipidemia, lipotoxicity, and oxidative stress. Among these, recent evidence highlights chronic inflammation as a key driver of disease progression toward advanced stages. Global scientific efforts have begun to uncover the molecular mechanisms sustaining the inflammatory response in MASLD, although these pathways remain only partially understood. Furthermore, therapeutic options for MASLD and MASH are currently limited, with no approved pharmacological treatments available for the advanced stages of the disease. This review aims to provide a comprehensive overview of the current understanding of the cellular and molecular mechanisms involved in the inflammatory processes underpinning MASLD and MASH while also outlining the key challenges that lie ahead in the development of effective therapies.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258070","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":"MZB1 Modulates Inflammatory Severity in Severe Acute Pancreatitis through an IgA-Associated Intestinal Barrier Axis.","authors":"Cong Chen, Guohui Xiao, Kaige Yang, Xujie Han, Yaqing Yang, Tong Zhou, Rongli Xie, Dan Xu, Jian Fei","doi":"10.1007/s10753-026-02534-2","DOIUrl":"10.1007/s10753-026-02534-2","url":null,"abstract":"<p><p>Severe acute pancreatitis (SAP) is characterized by excessive inflammatory responses that critically influence disease severity and systemic complications. Although innate immune activation has been extensively studied in SAP, the contribution of adaptive humoral immunity to inflammatory modulation during disease progression remains incompletely understood. In this study, we performed longitudinal single-cell RNA sequencing of peripheral blood mononuclear cells from patients with mild and severe acute pancreatitis to characterize immune alterations across disease stages. We observed dynamic immune remodeling, including increased engagement of B cell-associated humoral immune programs during later stages of severe disease. Among these changes, expression of the endoplasmic reticulum-resident protein MZB1 was prominently associated with plasma cell differentiation and immunoglobulin-related transcriptional activity. To investigate the functional relevance of MZB1, we employed genetic mouse models of experimental pancreatitis. Loss of MZB1 was associated with exacerbated pancreatic inflammation, impaired IgA production, and compromised intestinal barrier integrity. Together, these findings suggest that MZB1-associated humoral immune responses contribute to modulation of inflammatory severity in severe acute pancreatitis by supporting IgA-dependent intestinal barrier integrity and limiting secondary macrophage-driven inflammation.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224684","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":"Down-regulation of GPRC5A Confers Protection Against Periodontitis.","authors":"Yuhan Hu, Runxuan Liu, Xinxiao Chen, Lingling Shang","doi":"10.1007/s10753-026-02539-x","DOIUrl":"10.1007/s10753-026-02539-x","url":null,"abstract":"<p><p>Periodontitis, a common chronic inflammatory disease, causes connective tissue degradation, alveolar bone resorption, and tooth loss. G protein coupled receptor class C group 5 member A (GPRC5A) regulates chronic inflammation in several diseases, but its role in periodontitis remains unclear. This study investigated GPRC5A expression and function in periodontitis. In human tissues, GPRC5A expression was assessed by immunohistochemistry and quantitative real-time PCR (qRT-PCR). In vivo, adeno associated virus (AAV) mediated GPRC5A silencing was applied in a murine periodontitis model. In vitro, mechanistic studies used small interfering RNA (siRNA) knockdown, co-immunoprecipitation (Co-IP), mass spectrometry, and western blot in periodontal ligament cells (PDLCs). GPRC5A was upregulated in inflamed periodontal tissues, and its downregulation reduced alveolar bone loss and periodontitis severity in mice. GPRC5A knockdown suppressed inflammatory cytokine production and NF-κB activation in lipopolysaccharide (LPS) stimulated PDLCs. β-arrestin 2 (ARRB2) expression paralleled GPRC5A changes, and mass spectrometry/Co-IP identified eukaryotic elongation factor 2 (EEF2) as an ARRB2 binding partner. GPRC5A silencing reduced LPS induced ARRB2 expression and EEF2 phosphorylation. These data suggest a possible mechanistic link that GPRC5A downregulation mitigates periodontitis through the ARRB2‑EEF2 pathway, though direct evidence of causality is still needed.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224715","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 Sialomucin CD43 Drives Tuberculosis Immunopathology Across Different Host Genetic Backgrounds.","authors":"Estefanía Alemán-Navarro, Dulce A Mata-Espinosa, Manuel O López-Torres, Jorge A Barrios-Payán, Ángel F Flores-Alcantar, Erika I Melchy-Pérez, Rogelio Hernández-Pando, Yvonne Rosenstein","doi":"10.1007/s10753-026-02520-8","DOIUrl":"10.1007/s10753-026-02520-8","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a major global health challenge, with 10 million cases and 1.5 million deaths annually. Understanding the interplay between Mycobacterium tuberculosis (Mtb) and the host immune response is essential to better understand TB pathogenesis and develop new therapeutic strategies. Although the host immune bias strongly influences this interaction and shapes the ensuing response, the roles of specific immune receptors remain incompletely understood. Here, we investigated the role of CD43 in shaping the immune microenvironment during Mtb infection using Th2-biased BALB/c and Th1-biased C57BL/6 mice. CD43 deficiency consistently reduced pulmonary inflammation and improved survival in both strains, but through distinct mechanisms. In BALB/c mice, it enhanced early pulmonary cytokine production and promoted a more anti-inflammatory environment during late TB, leading to better control of bacterial growth and limiting the development of pneumonia. In contrast, in C57BL/6 mice, CD43 deficiency delayed pro-inflammatory cytokine responses and reduced the accumulation of inflammatory cells in the lungs, but it did not improve bacterial clearance. Together, these findings indicate that CD43 drives detrimental inflammation in TB through mechanisms that depend on the host immune bias, and highlight the complex and nuanced role of CD43 in regulating immune cell dynamics during TB progression, underscoring the need for tailored therapeutic approaches considering the context-dependent contributions of specific molecules such as CD43.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211080","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":"Multi-omics Integration of Single-cell and Spatial Transcriptomics with Tissue and Urine Proteomics Identifies TRIM28 as a Translationally Relevant Candidate Regulator in Acute Kidney Injury.","authors":"Kangyu Wang, Hao Wang, Yalong Zhang, Zijian Zhang, Changhong Xu, Hong Zhao, Jiaxuan Ma, Jiangwei Man, Li Yang","doi":"10.1007/s10753-026-02521-7","DOIUrl":"10.1007/s10753-026-02521-7","url":null,"abstract":"<p><p>Acute kidney injury (AKI) lacks disease-modifying therapies, partly because cell type-specific injury programs remain incompletely resolved and tissue mechanisms are not readily translated into clinically accessible biomarkers. We constructed a cross-scale, multi-omics atlas to prioritize candidate regulator linking renal injury circuitry with urine-detectable signals. Human single-cell, bulk, and spatial transcriptomics were integrated with mouse renal ischemia-reperfusion injury (RIRI) kidney proteomics and clinical urine proteomics. Overlap of differentially expressed genes and differentially abundant proteins nominated candidates, which were ranked by a random forest model. Immune remodeling was assessed by deconvolution and pathway enrichment, with spatial localization supported by reference-based deconvolution. Therapeutic tractability was explored by structure-based virtual screening, molecular docking, molecular dynamics simulation, and cellular thermal shift assay (CETSA). TRIM28 was evaluated in HK-2 hypoxia/reoxygenation (H/R) and mouse RIRI models using genetic perturbation, expression validation, and in vitro pharmacologic evaluation. Integration converged on five genes (TRIM28, HNRNPH1, ARHGEF10L, C1RL, and UCHL3), with TRIM28 showing the highest feature importance and links to inflammatory, immune, metabolic, and proliferative programs. AKI exhibited intensified intercellular communication and an innate-skewed immune landscape. TRIM28 was robustly upregulated in HK-2 H/R and mouse RIRI kidneys and was also directly detected in the human urine proteome. In HK-2 cells, TRIM28 knockdown dampened, whereas overexpression amplified, IL-17-linked inflammatory signaling and apoptotic responses. Docking-prioritized HY-N10592 improved viability, reduced H/R-associated TRIM28 induction, IL-17-linked output, and apoptotic marker activation, and showed CETSA-supported cellular engagement of TRIM28. This integrative framework prioritizes TRIM28 as a candidate regulator linking tubular injury mechanisms with clinically relevant urinary signals and nominates HY-N10592 as a candidate chemical tool with CETSA-supported cellular target engagement for further mechanistic and in vivo evaluation in AKI.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217617","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":"lncRNA-mRNA Co-expression Network Unveils Neutrophil Metabolic Reprogramming in Human Sepsis.","authors":"Peng Zhang, Fupeng Wang, Kang Zhao, Zeqing Miao, Yang Yu, Aiqing Wen, Huang Wu","doi":"10.1007/s10753-026-02532-4","DOIUrl":"10.1007/s10753-026-02532-4","url":null,"abstract":"<p><p>Sepsis is a life-threatening inflammatory syndrome driven by dysregulated immunity. Metabolic reprogramming and epigenetic regulation are now recognized as critical mechanisms underlying persistent immune cell alterations in sepsis. Neutrophils play a central role in sepsis by forming NETs, releasing inflammatory cytokines, and phagocytosing pathogens. During these processes, neutrophils undergo metabolic adaptation that supports their effector functions. Long non-coding RNAs (lncRNAs) have been implicated in multiple facets of sepsis progression, including the regulation of immune cell functions and organ injury. Recent studies further indicate that lncRNAs modulate metabolic reprogramming across various cell types during sepsis, highlighting extensive crosstalk between metabolic and epigenetic pathways. Nevertheless, the relationship between lncRNAs and metabolic reprogramming in neutrophils remains poorly understood. To better characterize the regulatory interplay between metabolic alterations and lncRNAs in neutrophils during sepsis, we performed RNA sequencing of neutrophils isolated from septic patients. We identified a set of hub differentially expressed genes enriched in amino acid metabolic processes and uncovered potential lncRNA networks that may regulate these genes. Our study delineates a broader landscape of neutrophil metabolic reprogramming in sepsis and provides a foundational co-expression network, offering new directions for investigating lncRNA-mediated amino acid metabolic alterations in neutrophils during sepsis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156395","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":"Skin Application of Inflammasome Inhibitor MCC950 Prevents Psoriasis-like Cutaneous Manifestations and Associated Systemic Inflammation.","authors":"Chiara Terranova, Alex Spitilli, Alisia Camporeale, Francesca Nigro, Federica Brugnoli, Silvia Grassilli, Valeria Bertagnolo, Fabio Casciano, Hasan Ayaz, Enrico Tassani, Chiara Ruzza, Claudio Trapella, Francesca Granucci, Davide Ferrari, Paola Secchiero, Eva Reali","doi":"10.1007/s10753-026-02535-1","DOIUrl":"10.1007/s10753-026-02535-1","url":null,"abstract":"<p><p>Psoriasis is a chronic, systemic inflammatory disease associated with cardiovascular and metabolic comorbidities. It is driven by a sustained immune response in the skin, orchestrated by keratinocytes and both innate and adaptive immune cells. The initial phase of the pathology remains largely unclear. It likely involves the activation of dendritic cells by stress signals from keratinocytes with the NLRP3 inflammasome potentially acting as a key innate sensor. Here we investigate the effects of the topical administration of the selective NLRP3 inhibitor MCC950, in the imiquimod-induced psoriasis-like inflammation model with the aim to achieve the inhibition of both cutaneous and systemic manifestations. Topical MCC950 effectively suppressed NLRP3 inflammasome activation by preventing pro-caspase-1 cleavage and generation of the active p20 subunit in the skin. Gene expression analysis showed that inhibition of NLRP3 suppressed the expression of psoriasis hallmark genes, including Il17, Tnf, S100a8/a9 and Il1b. Furthermore, network analysis identified NLRP3 as a central hub in the psoriasis-associated inflammatory module, supporting the concept that inflammasome inhibition dampens multiple downstream inflammatory pathways. In psoriasis-like condition, MCC950 reduced the skin infiltration of CD3⁺ T cells, CD11b⁺ myeloid and CD11c⁺ dendritic cells. Notably, MCC950 also prevented the systemic effects of psoriasis-like inflammation. Analysis in the spleen shows that it effectively prevented the phenotypic changes induced by psoriasis-like inflammation including the increased frequency of IL-17 A⁺ T cells. Finally, MCC950 prevented the systemic increase of serum IL-6. These findings highlight that upstream targeting of the NLRP3 inflammasome by MCC950 represents a promising strategy to inhibit both initiation and the systemic spread of psoriasis-like inflammation.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156468","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}