Immunology letters最新文献

{"title":"Functional Alterations in Colonic CD4+T and Regulatory T Cells Drive Immune Imbalance in Ulcerative Colitis.","authors":"Yan Long, Changsheng Xia, Xiaoyi Zheng, Jinghong Feng, Wenyi Li, Yinting Ma, Yuanyuan Sun, Xingyue Zeng, Chen Liu","doi":"10.1016/j.imlet.2025.107010","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.107010","url":null,"abstract":"<p><p>Immune imbalance plays a key role in the pathogenesis of ulcerative colitis (UC). The changes in CD4+ T cells and Treg cells in colonic T cells have an important relationship with UC. It is of great significance to elucidate the functional characteristics of CD4 cells and regulatory T (Treg) cells in UC patients. This study aimed to inquire into changes in functional markers of CD4 T cells and Tregs, including Helios, Bcl6, CTLA-4, CD226, TIGIT, PD-1 and ICOS. DSS-induced colitis was established in Balb/c mice and lymphocytes from spleen, mesenteric lymph nodes (MLNs), peripheral blood, and colon tissue were obtained. CD4+ T cells and Tregs were analyzed by flow cytometry. We found that Helios+ and Bcl-6+ proportions were increased in colonic CD4+ cells of DSS-induced colitis mice. CD4+FoxP3+CXCR5- Tregs were significantly elevated in the colon of colitis mice, with CTLA-4+ percentages increased. Naïve subsets in colonic CD4 and Tregs were significantly reduced, while effector T-cell subsets were increased in colitis mice. TIGIT+ and CD226+ percentages were significantly increased in both colonic CD4+ cells and Tregs of colitis mice. Both PD-1+ and ICOS+ percentages in colonic CD4 cells and the ICOS+ percentage in colonic Tregs were significantly increased in colitis mice. In conclusion, functional molecules related to CD4+ T cells and Tregs in colonic T cells are altered in UC, often adopting an activated phenotype. These changes may be associated with the pathogenesis of UC and could potentially serve as clinical therapeutic targets.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"107010"},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heparanase inhibition mitigates bleomycin-induced pulmonary fibrosis in mice by reducing M2 macrophage polarization","authors":"Long He ,&nbsp;Qianying Lv ,&nbsp;Jing Luo ,&nbsp;Yi-De Guo ,&nbsp;He Sun ,&nbsp;Ming Zong ,&nbsp;Lie-Ying Fan","doi":"10.1016/j.imlet.2025.107006","DOIUrl":"10.1016/j.imlet.2025.107006","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigates the involvement of heparanase in IPF pathogenesis and evaluates the therapeutic potential of heparanase inhibition.</div></div><div><h3>Methods</h3><div>Plasma heparanase levels were measured in IPF patients and healthy controls. Macrophage infiltration and heparanase expression in bronchoalveolar lavage fluid (BALF) were analyzed using immunofluorescence. Bleomycin (BLM)-induced pulmonary fibrosis mouse models were treated with the heparanase inhibitor OGT2115. Disease severity, macrophage polarization, and heparanase expression were assessed through histological staining, hydroxyproline content measurement, flow cytometry, immunofluorescence, Transmission Electron Microscopy and Western blot analysis.</div></div><div><h3>Results</h3><div>Elevated heparanase levels were found in the plasma of IPF patients and in macrophages from BALF. In BLM-induced mice, heparanase was predominantly expressed in M2 macrophages. OGT2115 treatment significantly reduced mortality, body weight loss, and fibrosis severity. Additionally, OGT2115 decreased M2 macrophage infiltration, attenuated lung fibrosis, and reduced autophagy markers LC3 I/II and P62.</div></div><div><h3>Conclusion</h3><div>Heparanase plays a crucial role in modulating M2 macrophage polarization and the progression of IPF. Targeting heparanase with OGT2115 effectively ameliorates pulmonary fibrosis and represents a promising therapeutic strategy for IPF management.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"274 ","pages":"Article 107006"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virus-specific antibody responses in severe acute respiratory syndrome coronavirus 2-infected and vaccinated individuals","authors":"Nicole Hartwig Trier ,&nbsp;Nadia Zivlaei ,&nbsp;Sisse Rye Ostrowski ,&nbsp;Erik Sørensen ,&nbsp;Margit Larsen ,&nbsp;Rimantas Slibinskas ,&nbsp;Evaldas Ciplys ,&nbsp;Jette Lautrup Frederiksen ,&nbsp;Gunnar Houen","doi":"10.1016/j.imlet.2025.107004","DOIUrl":"10.1016/j.imlet.2025.107004","url":null,"abstract":"<div><h3>Background</h3><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can have a serious course with many complications, especially in immunocompromised individuals. In such persons, other latent virus infections may contribute to disease pathology, in particular viruses which infect immune cells such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV).</div></div><div><h3>Methods</h3><div>In this study, serology-based assays were conducted to analyse antibody responses to SARS-CoV-2 spike protein (SP), EBV Epstein-Barr nuclear antigen (EBNA)-1 and CMV phosphoprotein (pp)52 in naturally SARS-CoV-2-infected individuals, non-infected healthy controls (HCs) and vaccinated healthy controls (VHCs) to identify an association between SARS-CoV-2 antibodies and EBV and CMV antibodies in order to determine whether latent EBV and CMV infected individuals are more prone to become infected with SARS-CoV-2. Moreover, SARS-CoV-2, EBV, and CMV antibody responses were characterized in serum from patients with relapsing-remitting multiple sclerosis (RRMS), a chronic inflammatory disease strongly associated with EBV infections, to determine whether the serologic virus antibody profile varies in immunocompromised RRMS individuals upon SARS-CoV-2 vaccinations compared to VHCs.</div></div><div><h3>Results</h3><div>Significantly elevated SP IgG, IgM and IgA levels were identified in SARS-CoV-2-infected immunocompetent individuals when compared to non-infected HCs. However, no correlation was found to serum antibodies between SARS-CoV-2, EBV, and CMV in individuals infected with SARS-CoV-2 and in VHCs, suggesting that latent infections with neither EBV nor CMV associates to SARS-CoV-2 infection. Moreover, no significant difference in SP IgG, IgA and IgM levels was observed between vaccinated RRMS patients and VHCs, indicating that the immune system of immune deficient RRMS patients and VHCs respond identical to SARS-CoV-2 vaccinations.</div></div><div><h3>Conclusion</h3><div>Collectively, SARS-CoV-2 SP antibody levels reflect the vaccination and infection history and do not associate with EBV and CMV serostatus.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"274 ","pages":"Article 107004"},"PeriodicalIF":3.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BENTA Disease or CARD11 Gain-of-Function? A Novel Variant with Atypical Features and a Literature Review.","authors":"L Baldini, B Keller, L Dewitte, C Passarelli, M Ginevrino, D Carli, D Montin, X Bossuyt, K Warnatz, F Licciardi","doi":"10.1016/j.imlet.2025.107005","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.107005","url":null,"abstract":"<p><strong>Introduction: </strong>The CARD11 (Caspase Recruitment Domain Family Member 11) gene encodes a scaffold protein critical for NF-κB signaling, regulating B-cell differentiation and T-cell effector functions. Gain-of-function (GOF) mutations in CARD11 cause BENTA disease (B cell Expansion with NF-κB and T cell Anergy), an autosomal dominant disorder typically presenting with early-onset polyclonal B-cell lymphocytosis, splenomegaly, lymphadenopathy, and recurrent infections.</p><p><strong>Methods: </strong>We describe three related patients harboring a novel CARD11-GOF mutation (D357E), presenting with a BENTA phenotype with atypical features, including high IgM levels and a normal B-cell count, with life-threatening HLH in one case. Additionally, we conducted a systematic literature review using PubMed and EMBASE to identify previously reported cases of CARD11 GOF mutations.</p><p><strong>Results: </strong>In vitro functional analysis demonstrated that the D357E variant activates the NF-κB signaling pathway in primary lymphocytes and in HEK293T cells transfected with mutant CARD11. Our literature review identified 13 studies describing 29 patients. Notably, HLH emerged as a common complication of CARD11 GOF mutations (18.8%), while B-lymphocytosis -though frequent- was not universally present.</p><p><strong>Conclusion: </strong>We identified a novel pathogenic CARD11 variant and described its atypical phenotype, further expanding the clinical spectrum of CARD11 GOF disorders. These findings underscore the need for increased awareness of HLH risk in patients with CARD11 GOF mutations.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"107005"},"PeriodicalIF":3.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibodies and therapeutic antibodies against complement factor H","authors":"Saskia Nugteren ,&nbsp;Haiyu Wang ,&nbsp;Cees van Kooten ,&nbsp;Kyra A. Gelderman ,&nbsp;Leendert A. Trouw","doi":"10.1016/j.imlet.2025.107002","DOIUrl":"10.1016/j.imlet.2025.107002","url":null,"abstract":"<div><div>The complement system is a crucial part of our immune defense as, upon recognition, it can kill pathogens fast and effectively. However, misguided complement activation could cause damage to host tissues. Therefore, a well-controlled regulation of the complement system is a necessity to prevent collateral damage. Regulation is achieved by several complement inhibitory proteins, acting at different levels of the complement system. One of these complement regulators is factor H, the main regulator of the alternative complement activation pathway. Factor H can regulate the complement system both in fluid-phase and on the host cell surface by, for example, acting as co-factor for factor I, inactivating C3b. The functional properties of factor H are located within different regions of the protein. Functional impairment of factor H, either because of genetic variants, competing proteins such as the factor H-related proteins and proteins from certain pathogens, but also the presence of autoantibodies will impact on complement activation. However, exact consequences are dependent on the region within factor H that is affected. Autoantibodies binding to factor H have been shown to inhibit several regulatory functions of factor H, which is observed in diseases such as membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome. As more recently the presence of anti-factor H autoantibodies has also been discovered in several other diseases, ranging from autoimmune diseases to cancer, this review provides an overview of the presence of factor H autoantibodies described in these diseases. Factor H autoantibodies are reported to have inhibitory, or enhancing, effects on factor H, depending on the epitopes that are recognized. Formal conclusions about the pathogenicity of the factor H autoantibodies in some of these diseases cannot be drawn yet. Importantly, understanding the binding and functional impact of anti-factor H (auto)antibodies will allow targeted interventions to diminish pathological consequences of anti-factor H autoantibodies but may also open up additional avenues for the use of anti-factor H antibodies as therapeutic agents.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"274 ","pages":"Article 107002"},"PeriodicalIF":3.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Connecting the dots: Mitochondrial transfer in immunity, inflammation, and cancer","authors":"Valentina Artusa ,&nbsp;Lara De Luca ,&nbsp;Mario Clerici ,&nbsp;Daria Trabattoni","doi":"10.1016/j.imlet.2025.106992","DOIUrl":"10.1016/j.imlet.2025.106992","url":null,"abstract":"<div><div>Mitochondria are more than mere energy generators; they are multifaceted organelles that integrate metabolic, signalling, and immune functions, making them indispensable players in maintaining cellular and systemic health. Mitochondrial transfer has recently garnered attention due to its potential role in several physiological and pathological processes. This process involves multiple mechanisms by which mitochondria, along with mitochondrial DNA and other components, are exchanged between cells. In this review, we examine the critical roles of mitochondrial transfer in health and disease, focusing on its impact on immune cell function, the resolution of inflammation, tissue repair, and regeneration. Additionally, we explore its implications in viral infections and cancer progression. We also provide insights into emerging therapeutic applications, emphasizing its potential to address unmet clinical needs.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"274 ","pages":"Article 106992"},"PeriodicalIF":3.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The regulatory effect and molecular mechanism of Epstein-Barr virus protein LMP-1 in SLE susceptibility gene expression","authors":"Xiang Zhang ,&nbsp;Shouci Hu ,&nbsp;Puchang Luo ,&nbsp;Zhiyu Li ,&nbsp;Zhejun Chen ,&nbsp;Cong Xia ,&nbsp;Linxuan Fan ,&nbsp;Rongqun Li ,&nbsp;Hongbo Chen","doi":"10.1016/j.imlet.2025.106993","DOIUrl":"10.1016/j.imlet.2025.106993","url":null,"abstract":"<div><div>The development of systemic lupus erythematosus (SLE) involves both genetic and environmental factors. Epstein–Barr virus (EBV) infection has been implicated in SLE pathogenesis, particularly through the activity of latent membrane protein 1 (LMP-1). This study aimed to explore the role of LMP-1 in regulating susceptibility gene expression in SLE. Peripheral blood mononuclear cells (PBMCs) from SLE patients and H9 T cells were used to investigate this mechanism both in vivo and in vitro. RNA-seq analysis revealed that LMP-1 and the SLE susceptibility gene AT-rich interactive domain 5B (ARID5B) were significantly upregulated in SLE. Overexpression of LMP-1 in H9 T cells further increased ARID5B expression. Histone H3K27 methylation, catalyzed by enhancer of zeste homolog 2 (EZH2), was significantly elevated, suggesting epigenetic modifications play a role in this regulation. H3K27 methylation was studied due to its known involvement in transcriptional repression and chromatin remodeling in autoimmune diseases. Furthermore, phosphorylated p65 (p-p65), a marker of nuclear factor-kappa-B (NF-κB) pathway activation, was increased. Blocking the NF-κB signaling pathway reduced ARID5B expression, indicating that LMP-1 may regulate susceptibility genes through NF-κB signaling and histone modifications. These findings suggest that EBV LMP-1 contributes to SLE pathogenesis by epigenetically modulating susceptibility gene expression and activating inflammatory pathways.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106993"},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLAMF8 regulates Fc receptor-mediated phagocytosis in mouse macrophage cells through PI3K-Akt signaling","authors":"Zhihao Liu ,&nbsp;Jing Hu ,&nbsp;Xingzhi Han ,&nbsp;Li Li ,&nbsp;Haiqing Niu ,&nbsp;Xin Zhang ,&nbsp;Ning Wang ,&nbsp;Xiao Shi ,&nbsp;Liuqi Sang ,&nbsp;Qun Zhang ,&nbsp;Xiaoping Qian","doi":"10.1016/j.imlet.2025.106990","DOIUrl":"10.1016/j.imlet.2025.106990","url":null,"abstract":"<div><div>Emerging studies have demonstrated that phagocytosis checkpoints, which promote tumor-mediated immune evasion, are potential targets for cancer immunotherapy. In this study, the TCGA colorectal cancer (CRC) dataset and our RNA sequencing dataset suggested that <em>SLAMF8</em> expression is significantly positively correlated with the expression levels of multiple phagocytosis checkpoint molecules. In vitro, we confirmed that <em>SLAMF8</em> significantly regulated the phagocytosis of mouse CRC cells. RNA sequencing revealed that the expression of genes that promote Fc receptor (FcR)-mediated phagocytosis, such as FCGR1, FCGR3, FCGR2b, FCGR4, and ITGAM, was significantly upregulated after <em>SLAMF8</em> knockdown. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results suggested that the significantly enriched signaling pathways after <em>SLAMF8</em> knockdown or overexpression included the PI3K-Akt signaling pathway. The protein expression levels of p-PI3K and p-Akt were significantly increased after <em>SLAMF8</em> knockdown. When PI3K inhibitors and Fc blockers were added after <em>SLAMF8</em> knockdown, mouse macrophage phagocytosis, and FcR expression decreased. Our results suggest that <em>SLAMF8</em> may impair FcR-mediated phagocytosis through the PI3K-Akt signaling pathway and negatively regulate the antitumor immune response.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106990"},"PeriodicalIF":3.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil extracellular traps and reactive oxygen species: Predictors of prognosis in bladder cancer","authors":"Zahra Mansourabadi ,&nbsp;Mohammad-Ali Assarehzadegan ,&nbsp;Fereshteh Mehdipour ,&nbsp;Ali Ariafar ,&nbsp;Zahra Faghih ,&nbsp;Elahe Safari","doi":"10.1016/j.imlet.2025.106991","DOIUrl":"10.1016/j.imlet.2025.106991","url":null,"abstract":"<div><div>Neutrophils, the most abundant leukocytes in circulation, have become the subject of intensive research due to growing evidence of their role as modulators of cancer with both anti- and pro-tumorigenic effects. However, their prognostic function related to the release of neutrophil extracellular traps (NETs) and production of reactive oxygen species (ROS) has not yet been elucidated in the context of bladder cancer (BC). This study aimed to evaluate the ability of circulating neutrophils from BC patients to undergo NETosis and produce ROS—both spontaneously and following activation with phorbol 12-myristate 13-acetate (PMA)—using flow cytometry and immunofluorescence techniques. Their relevance to clinicopathological characteristics was also evaluated. Our results showed that PMA-treated neutrophils had increased early NETosis in patients with stage II (<em>P</em> = 0.048) and T2 (<em>P</em> = 0.014) compared to those with stage III and T3, respectively. These cells also showed a significant increase in ROS production in patients with T2 compared to those with T3 (<em>P</em> = 0.026) and T4 (<em>P</em> = 0.014), as well as in patients with stage II compared to stage IV (<em>P</em> = 0.048). Additionally, spontaneous ROS production was higher in patients without lymphovascular invasion than in those with invasion (<em>P</em> = 0.013). The increased activity of neutrophils observed in earlier stages (stage II and T2) suggests a potential protective mechanism in the early phases of cancer progression. It also highlights NETosis and ROS production by neutrophils as possible biomarkers for assessing disease progression. These findings provide insights into the complex interactions of neutrophils within the tumor microenvironment and lay the groundwork for further investigations into targeted therapies, potentially improving prognostic evaluations and treatment outcomes for patients.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106991"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nobiletin ameliorates monosodium urate-induced gouty arthritis in mice by enhancing AMPK/mTOR-mediated autophagy to inhibit NF-κB/NLRP3 inflammasome activation","authors":"Zhiyong Liu ,&nbsp;Aichun Chu ,&nbsp;Zhiqian Bai ,&nbsp;Chao Yang","doi":"10.1016/j.imlet.2025.106982","DOIUrl":"10.1016/j.imlet.2025.106982","url":null,"abstract":"<div><h3>Background</h3><div>Gouty arthritis (GA) is a common rheumatic disease caused by the release of monosodium urate crystal (MSU) deposits into joint space. Nobiletin is a polymethoxylated flavonoid isolated from citrus fruits and has many beneficial activities. This study aimed to elucidate the therapeutic efficacy of nobiletin in GA and to reveal its potential mechanisms.</div></div><div><h3>Methods</h3><div>Phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 macrophages were primed with lipopolysaccharide (LPS) and then stimulated with MSU crystals in the presence or absence of nobiletin. Cell viability as well as the levels of proinflammatory cytokines, pathway-related proteins, NLRP3 inflammasomes, and autophagy-related proteins were evaluated. MSU was used to induce GA in mice. Hematoxylin-eosin staining was conducted to assess histological morphology changes. Immunofluorescence staining was performed to measure LC3 expression in THP-1 cells and ankle joint tissues.</div></div><div><h3>Results</h3><div>For <em>in vitro</em> analysis, nobiletin reduced LPS and MSU-induced cell viability inhibition. Additionally, nobiletin inhibited inflammation and NF-κB/NLRP3 pathway in THP-1 cells. Moreover, nobiletin inhibited the activation of NLRP3 inflammasome by promoting AMPK/mTOR-mediated autophagy. For <em>in vivo</em> analysis, nobiletin attenuated MSU-induced GA in mice. Additionally, nobiletin suppressed inflammation and NF-κB/NLRP3 pathway and promoted tissue autophagy in GA mice.</div></div><div><h3>Conclusion</h3><div>Nobiletin prevents MSU-induced GA in mice by inhibiting NF-κB/NLRP3 inflammasome activation through AMPK/mTOR-mediated autophagy.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"274 ","pages":"Article 106982"},"PeriodicalIF":3.3,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}