Cytokine最新文献

{"title":"Unlocking potentials of a prenylated flavonoid: Xanthohumol's role in combating inflammatory conditions and Rhematic diseases","authors":"Farag M.A. Altalbawy ,&nbsp;Ahmed Hussein Zwamel ,&nbsp;Ashok Kumar Bishoyi ,&nbsp;Suhas Ballal ,&nbsp;Rishiv Kalia ,&nbsp;Kamal Kant Joshi ,&nbsp;Subhashree Ray ,&nbsp;Atreyi Pramanik ,&nbsp;Jasur Rizaev ,&nbsp;Khursheed Muzammil","doi":"10.1016/j.cyto.2025.157092","DOIUrl":"10.1016/j.cyto.2025.157092","url":null,"abstract":"<div><div>Xanthohumol, a prenylated flavonoid derived from hops (<em>Humulus lupulus</em>), has garnered significant attention for its multifaceted therapeutic potential. This review highlights xanthohumol's ability to modulate key signaling pathways, including NF-κB, STAT3, and Nrf2, which are central to inflammation, oxidative stress, and cancer progression. As a flavonoid, xanthohumol exhibits potent antioxidant and anti-inflammatory properties, making it effective in alleviating inflammatory conditions such as osteoarthritis, rheumatoid arthritis, and inflammatory bowel disease. In cancer, xanthohumol demonstrates remarkable efficacy by inhibiting tumor growth, angiogenesis, and metastasis through the suppression of critical pathways like CXCR4 and STAT3. Preclinical studies have shown that xanthohumol selectively targets cancer cells while sparing normal cells, underscoring its potential as a safe and effective anticancer agent. Beyond its anti-inflammatory and anticancer effects, xanthohumol also plays a significant role in metabolic regulation. It improves glucose homeostasis, lipid metabolism, and gut microbiota composition, offering therapeutic benefits for metabolic syndrome and diabetes. Clinical trials and preclinical research further validate xanthohumol's safety and efficacy, with emerging evidence supporting its use in managing chronic diseases. This review provides a comprehensive overview of xanthohumol's mechanisms of action, therapeutic applications, and future directions in clinical research, positioning it as a promising natural compound for the prevention and treatment of a wide range of diseases.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157092"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of HMGB1 in central nervous system (CNS) diseases: mechanisms and therapeutic perspectives","authors":"Ou Du,&nbsp;Yi-Jin Wu,&nbsp;Meng-Yang Li,&nbsp;Jun-Rong Du","doi":"10.1016/j.cyto.2025.157099","DOIUrl":"10.1016/j.cyto.2025.157099","url":null,"abstract":"<div><div>Central nervous system (CNS) diseases represent a major global health burden and are among the leading causes of disability and mortality worldwide. The pathological mechanisms underlying CNS disorders are complex and multifactorial, involving processes such as neuroinflammation, oxidative stress, neuronal damage, and synaptic dysfunction. High-mobility group box 1 (HMGB1), a member of the high-mobility group box (HMGB) protein family, is predominantly localized in the nucleus under physiological conditions, where it contributes to DNA repair, transcriptional regulation, and other cellular functions. However, in various CNS pathologies—including stroke, traumatic brain injury (TBI), Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), glioblastoma (GBM), epilepsy, depression, multiple sclerosis (MS), and schizophrenia—HMGB1 is released or secreted into the extracellular space. There, it plays a key role in regulating neuroinflammation, cell death, cell migration, and tissue damage and repair, thereby contributing to disease pathogenesis and progression. HMGB1 not only functions as a critical regulator in the progression of CNS diseases but also serves as a biomarker for predicting poor clinical outcomes. Moreover, a growing body of evidence indicates that therapeutic strategies targeting HMGB1 can significantly alleviate pathological damage in various CNS disorders, highlighting its potential as a promising therapeutic target. This review comprehensively summarizes the structure, post-translational modifications, release mechanisms, and receptor systems of HMGB1, along with its roles and mechanisms in CNS diseases. It also discusses the potential of HMGB1 as a biomarker and examines emerging HMGB1-targeted therapeutic strategies, aiming to provide a theoretical foundation for the treatment and drug development of CNS disorders.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157099"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Group 2 innate lymphoid cells (ILC2s) in childhood allergic diseases: A review of the mechanisms and therapeutic advances","authors":"Yun Zhang ,&nbsp;Yaling Wu ,&nbsp;Yingying Wang ,&nbsp;Haoquan Zhou","doi":"10.1016/j.cyto.2025.157101","DOIUrl":"10.1016/j.cyto.2025.157101","url":null,"abstract":"<div><div>Recent advances in pediatric immunology have clarified the pivotal role of group 2 innate lymphoid cells (ILC2s) in the pathophysiology of childhood allergic diseases. As key components of the innate immune system, ILC2s mediate the initiation and progression of these disorders. Their activation is triggered primarily by epithelial-derived cytokines, whose expression is highly elevated in children with allergies. Upon activation, ILC2s rapidly secrete type 2 cytokines, driving disease-specific pathogenesis. In allergic asthma, airway ILC2 expansion exacerbates eosinophilic inflammation, airway hyperresponsiveness, and remodeling; in allergic rhinitis, nasal mucosal ILC2 activation induces typical symptoms; and in food allergies, intestinal mucosal ILC2s cause epithelial damage and increased permeability, promoting allergic progression. These mechanistic insights have underpinned the development of innovative therapies. Clinical trials have confirmed the efficacy of treatments targeting ILC2-derived cytokines or their receptors: anti-IL-5 monoclonal antibodies (targeting the IL-5 ligand), anti-IL-13 monoclonal antibodies (targeting the IL-13 ligand), and anti-IL-4Rα monoclonal antibodies (targeting IL-4 receptor α and blocking IL-4/IL-13 signaling) are promising treatments for specific childhood allergic diseases. Emerging strategies targeting ILC2 activation pathways and modulating the microbiome to regulate ILC2 activity are under active investigation. Collectively, the past five years of research have improved the understanding of the mechanisms underlying childhood allergic diseases and established new treatment paradigms, with great potential to optimize clinical management and improve the outcomes of pediatric patients with allergies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157101"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promoter variants of tumor necrosis factor-alpha (G-308 a: rs1800629 and C-857 T:rs1799724) are linked to type 1 diabetes: A meta-analysis and trial sequential analysis","authors":"Shengnan Zhang,&nbsp;Zhenyu Li,&nbsp;Xiaodong Yang","doi":"10.1016/j.cyto.2025.157082","DOIUrl":"10.1016/j.cyto.2025.157082","url":null,"abstract":"<div><h3>Introduction</h3><div>Tumor necrosis factor-alpha (TNF-α) is associated with type 1 diabetes through complex immunological and metabolic pathways, highlighting its multifaceted role. Genetic differences, particularly in the TNF-α gene promoter region, influence individual susceptibility to type 1 diabetes by altering gene expression. Numerous studies have examined the link between TNF-α polymorphisms and type 1 diabetes in various populations, yielding inconsistent results. This research explores the relationship between TNF-α and type 1 diabetes through a detailed meta-analysis of existing studies.</div></div><div><h3>Materials and methods</h3><div>This meta-analysis examined four SNPs in the TNF-α gene promoter region: G-238 A, G-308 A, C-587 T, and T-1031C. Literature searches were conducted using PubMed, ScienceDirect, Google Scholar, Embase, Web of Science, and Scopus. Relevant articles were systematically reviewed, and qualifying studies were selected based on specific inclusion and exclusion criteria. The analysis was performed using Comprehensive Meta-Analysis software, version 4.</div></div><div><h3>Results</h3><div>Twenty-four case-control studies were suitable for examining the link between TNF-α polymorphisms and T1D susceptibility. Genetic comparison models showed an association between the TNF-α G-308 A and C-857 T variants and T1D risk, and sensitivity analysis confirmed these findings. Trial sequential analysis further validated the genetic relationship between TNF-α promoter variants (G-308 A and C-857 T) and indicated that sufficient studies were available for a conclusive meta-analysis. Conversely, no significant association was found between the promoter polymorphisms G-238 A and T-1031C and T1D onset, and TSA suggested the need for further research across diverse populations.</div></div><div><h3>Conclusions</h3><div>Variations in the TNF-α promoter at positions G-308 A and C-857 T are linked to an increased risk of T1D.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157082"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical observation of anti-PD-1/PD-L1 immunotherapy plus concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma","authors":"Xudong Sun ,&nbsp;Dongmei Wu ,&nbsp;Guangcheng Ding ,&nbsp;Xueying Zhang ,&nbsp;Changli Shi ,&nbsp;Yulong Tian","doi":"10.1016/j.cyto.2025.157096","DOIUrl":"10.1016/j.cyto.2025.157096","url":null,"abstract":"<div><h3>Objective</h3><div>This study analyzed the efficacy of the PD-1 inhibitor Sintilimab combined with concurrent chemoradiotherapy (CCRT) in patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC).</div></div><div><h3>Methods</h3><div>A retrospective study involved 177 individuals with unresectable advanced ESCC, treated with anti-PD-1/PD-L1 immunotherapy combined with CCRT. Patients were categorized into three groups: combined positive score (CPS) ≥ 50, 1 &lt; CPS &lt; 50, and CPS &lt; 1. Clinical data and laboratory markers (carcinoembryonic antigen [CEA] and squamous cell carcinoma antigen [SCC-Ag]) were collected at baseline, 6, 12, and 24 months. PET/CT and CT scans assessed tumor response, ORR, and DCR. Kaplan-Meier curves analyzed the impact of CPS scores on progression-free survival (PFS) and overall survival (OS). Baseline data were matched at a 1:1 ratio by propensity score matching, followed by Cox regression analyses.</div></div><div><h3>Results</h3><div>No noticeable differences were present among the groups regarding gender, tumor location, prior chemotherapy, prior radiotherapy, or laboratory markers. After treatment, CEA and SCC-Ag levels significantly decreased, with the lowest levels observed at 24 months post-treatment. Higher CPS scores were associated with reduced CEA and SCC-Ag levels. PD-L1-positive groups (CPS &gt; 1) had higher ORR and DCR than the PD-L1-negative group. As CPS scores increased, PFS and OS were significantly prolonged. Serum fibrinogen, CEA and SCC-Ag were identified as independent risk factors for OS; Serum CEA and SCC-Ag were independent risk factors affecting PFS.</div></div><div><h3>Conclusion</h3><div>Higher CPS scores are associated with improved PFS and OS in patients with locally advanced ESCC receiving anti-PD-1/PD-L1 immunotherapy combined with CCRT.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157096"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in lipid nanoparticle delivery systems for targeted cytokine immunotherapy in autoimmune disorders","authors":"Dilpreet Singh","doi":"10.1016/j.cyto.2025.157098","DOIUrl":"10.1016/j.cyto.2025.157098","url":null,"abstract":"<div><div>Autoimmune diseases result from dysregulated immune responses, primarily driven by CD4+ T cell imbalances, leading to chronic inflammation and tissue destruction. Conventional cytokine-based therapies, including IL-2 for regulatory T cell (Treg) expansion and IL-6 or IL-17 inhibition for inflammation suppression, have shown promise in modulating immune responses. However, challenges such as systemic toxicity, short half-life, and off-target effects limit their therapeutic efficacy. Lipid nanoparticles (LNPs) have emerged as a next-generation drug delivery platform, offering enhanced cytokine stability, targeted cellular uptake, and controlled release, thereby overcoming limitations associated with free cytokine administration. Preclinical studies have demonstrated that LNP-IL-2 selectively expands Tregs in type 1 diabetes models, while IL-10-loaded LNPs suppress synovial inflammation in rheumatoid arthritis more effectively than conventional cytokine therapies. Optimization of ligand density and affinity on LNP surfaces is emerging as a key determinant of CD4⁺ T cell targeting efficiency. Additionally, LNP-encapsulated siRNA targeting IL-6 and IL-23 has shown superior suppression of inflammatory pathways in lupus and psoriasis. These findings underscore the potential of LNP-mediated cytokine delivery to precisely modulate CD4+ T cell function, restoring immune homeostasis in autoimmune diseases. Despite promising preclinical and early clinical data, challenges remain, including optimizing biodistribution, ensuring selective T cell targeting, and mitigating immune activation risks. This review provides an in-depth analysis of CD4+ T cell subsets in autoimmunity, the advantages of LNP-based cytokine therapies, and their translational potential. The integration of LNP technology into cytokine immunotherapy offers a novel, minimally toxic, and durable approach to reprogramming immune responses, paving the way for precision medicine in autoimmune disease management.</div></div><div><h3>Significance</h3><div>Autoimmune disorders are characterized by chronic inflammation driven by dysregulated cytokine activity. Traditional cytokine therapies often suffer from systemic toxicity and limited targeting precision. This manuscript highlights recent advancements in lipid nanoparticle (LNP) technology for the targeted delivery of cytokines, offering enhanced therapeutic efficacy and safety. By enabling precise modulation of immune responses at disease sites, LNP-based delivery systems represent a transformative approach in immunotherapy. This review underscores the potential of LNPs to overcome current limitations in autoimmune treatment, paving the way for next-generation precision medicine strategies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157098"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-8-, IL-12-, and VEGF-producing peripheral blood mononuclear cells enable differentiation between vertebral osteomyelitis and degenerative spinal diseases","authors":"Julia Schenk ,&nbsp;Martin Thelen ,&nbsp;Hans Anton Schlößer ,&nbsp;Esther Mahabir","doi":"10.1016/j.cyto.2025.157104","DOIUrl":"10.1016/j.cyto.2025.157104","url":null,"abstract":"<div><div>Vertebral osteomyelitis (VO) is a rare but serious spinal infection that presents significant challenges in early diagnosis and treatment. Diagnostic delays can result in severe complications, including neurological deficits, sepsis, organ failure, and death. In this study, we investigated the immune cell source of candidate cytokines – IL-6, IL-8, IL-12, and VEGF – with the aim of distinguishing VO from degenerative spinal diseases. Peripheral blood samples were collected pre-operatively and 40 to 56 days post-operatively. Cytokine production by major immune cell subsets within peripheral blood mononuclear cells (PBMCs) was analyzed using intracellular flow cytometry. Our findings indicate that pre-operative differentiation between VO and degenerative spinal diseases is feasible, particularly based on IL-8-positive CD8⁺ T-cells, IL-12-positive CD45⁺ lymphocytes, and VEGF-positive cells (including CD45⁺ cells, B-cells, T-cells, and CD8⁺ T-cells).</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157104"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage USP14 suppresses Wnt/β-catenin signaling via NLK deubiquitination to enhance immune response","authors":"Mingming Zhao ,&nbsp;Junjie Shi ,&nbsp;Xinqi Wei ,&nbsp;Wenze Tian ,&nbsp;Yuee Chen","doi":"10.1016/j.cyto.2025.157079","DOIUrl":"10.1016/j.cyto.2025.157079","url":null,"abstract":"<div><div>Macrophages are key immune cells that regulate the body's immune response by promoting the release of inflammatory cytokines upon recognition of both endogenous and exogenous pathogens. USP14, a critical deubiquitinase, plays a vital role in various cellular processes, especially in modulating immune responses. This study aims to investigate the role of USP14 in regulating macrophage immune responses. USP14 overexpression and knockdown were performed in RAW264.7 cells and mouse bone marrow macrophages via plasmid transfection and lentiviral infection, respectively. Our research demonstrates that USP14 overexpression amplified the LPS-induced inflammatory response and promoted macrophage migration, whereas USP14 knockdown produced the opposite effects. USP14 interacts with NLK, thereby attenuating Wnt/β-catenin signaling and concurrently activating the NF-κB pathway in macrophages. USP14 facilitates the deubiquitination of NLK, thereby stabilizing its activity. Moreover, the USP14 inhibitor IU1 reduces the LPS-induced inflammatory response in macrophages. Mechanistically, macrophage USP14 facilitates the deubiquitination of NLK, thereby maintaining its activity, inhibiting the Wnt/β-catenin pathway, activating the NF-κB pathway, and enhancing the cellular immune response.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157079"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triptolide impacts CSF1R expression andreprograms the suppressive function of myeloid-derived suppressor cells via targeting the ER stress pathway","authors":"Huijie Huang ,&nbsp;Guojun Liang ,&nbsp;Yaozong He ,&nbsp;Hongyu Wang ,&nbsp;Xiaowen Lin ,&nbsp;Ziling Zhao ,&nbsp;Enyu Liang ,&nbsp;Yunxiu Wang ,&nbsp;Jian-xin Peng ,&nbsp;Hong-wei Sun ,&nbsp;Min He","doi":"10.1016/j.cyto.2025.157068","DOIUrl":"10.1016/j.cyto.2025.157068","url":null,"abstract":"<div><div>Triptolide (TPT) is a natural compound in herbal remedies with anti-inflammatory and anti-tumor properties. The study aimed to investigate the therapeutic effect of triptolide treatment on Myeloid-derived suppressor cells (MDSCs) in Hepatocellular Carcinoma (HCC). Single-cell transcriptomic profiling of liver tumor biopsies identified (Colony-Stimulating Factor 1 Receptor) CSF1R⁺ MDSCs as a distinct MDSCs lineage in HCC patients, which exhibited a positive correlation with the severity of HCC. Flow cytometric analysis confirmed CSF1R⁺ MDSCs were enriched in the peripheral blood and tumor tissue of HCC patients. Elevated CSF1R expression were highly expressed on the polymorphonuclear-MDSCs (PMN-MDSCs) subset specifically. Notably, PERK-mediated endoplasmic reticulum (ER) stress activation contributed to CSF1R induction, as evidenced by inhibiting the activities of PERK, but not IRE1α or ATF6, successfully attenuated the frequency of CSF1R⁺ MDSCs. Moreover, TPT dose-dependently diminished MDSCs and CSF1R⁺ MDSCs frequencies, alongside with alleviating the immunosuppressive capability on T cell proliferation. Further investigation revealed TPT treatment suppressed phosphorylation of PERK, as well as the protein levels of ATF4 and C/EBPβ. Our results underscore the role of ER stress-induced CSF1R expression in driving HCC disease progression by promoting the immunosuppressive effects of MDSCs, and identify CSF1R as a promising immunosuppressive target of TPT in HCC therapy.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157068"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXC1 ameliorates the disease progression of psoriasis through transcriptional upregulation of SOCS3","authors":"Ziyu Duan,&nbsp;Ke Sha,&nbsp;Lu Bian,&nbsp;Yujiao Sun","doi":"10.1016/j.cyto.2025.157078","DOIUrl":"10.1016/j.cyto.2025.157078","url":null,"abstract":"<div><div>Psoriasis is a chronic inflammatory skin disease, and Forkhead box C1 (FOXC1) has been shown to display inhibitory effects on both inflammation and oxidative stress. However, the exact role and underlying mechanism of FOXC1 in the context of psoriasis are yet to be fully explored and clarified. In this study, imiquimod (IMQ) induced experimental psoriasis in mice, and M5-induced keratinocytes (HaCaT) were used to examine the effect of FOXC1 in psoriasis. FOXC1 is downregulated in IMQ-induced mice and M5-treated HaCat cells. Upon overexpressing FOXC1, IMQ-induced psoriasiform skin lesions in mice were improved. Specifically, upregulating FOXC1 in IMQ mice resulted in a reduction in the concentrations of key inflammatory cytokines, including S100A8, S100A9, TNF-α, IL-1β, IL-6, and IL-17 A, effectively alleviating the inflammatory response. Moreover, FOXC1 overexpression exhibited a beneficial effect on oxidative stress, decreased ROS generation, reduced MDA content, and restored the activity of SOD in the skin lesions of psoriasis mice. Similar results were obtained when examining the effect of FOXC1 in M5-induced HaCaT cells. Further investigations suggested that the suppressor of cytokine signaling 3 (SOCS3) might be involved in this process. FOXC1 was found to transcriptionally upregulate the expression of SOCS3 in HaCaT cells. In M5-induced HaCaT cells, the inhibition of SOCS3 reversed the protective effect caused by FOXC1 overexpression, upregulated the expression of S100A8 and S100A9, and promoted ROS levels. Therefore, our findings reveal that the upregulation of FOXC1 ameliorates the disease progression of psoriasis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157078"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145660176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}