IF 3.7 3区医学

Cytokine Pub Date : 2026-05-04 DOI: 10.1016/j.cyto.2026.157162

C Moermans, S Graff, L Medard, H Nekoee, A-F Donneau, M S Njock, C Kempeneers, N Bricmont, R Bonhiver, S Gerday, N Nasir, C Poulet, V Paulus, F Guissard, C Sanchez, F Schleich, R Louis

引用次数: 0

Corrigendum to "TGF-β signaling and the interaction between platelets and T-cells in tumor microenvironment: Foes or friends?" [Cytokine 150 (2022) 155772]. 肿瘤微环境中TGF-β信号和血小板与t细胞的相互作用：是敌是友？[细胞因子150(2022)155772]。

IF 3.7 3区医学

Cytokine Pub Date : 2026-04-25 DOI: 10.1016/j.cyto.2026.157161

Azadeh Sadat Razavi, Maryam Mohtashami, Sepideh Razi, Nima Rezaei

引用次数: 0

Oxidative stress activates HIF-1α to mediate the secretion of CXCL9 and CXCL10 in keratinocytes and trigger the abnormal immune response in vitiligo 氧化应激激活HIF-1α介导角质形成细胞CXCL9和CXCL10的分泌，引发白癜风异常免疫应答

IF 3.7 3区医学

Cytokine Pub Date : 2026-04-01 Epub Date: 2026-02-03 DOI: 10.1016/j.cyto.2026.157123

Ruolin Chen , Xiaoxue Jiang , Yuxi Wang , Zhiyuan Shi , Xinyi Liu , Duo Meng , Xian Jiang , Jinpeng Lv , Yan Cao

{"title":"Oxidative stress activates HIF-1α to mediate the secretion of CXCL9 and CXCL10 in keratinocytes and trigger the abnormal immune response in vitiligo","authors":"Ruolin Chen , Xiaoxue Jiang , Yuxi Wang , Zhiyuan Shi , Xinyi Liu , Duo Meng , Xian Jiang , Jinpeng Lv , Yan Cao","doi":"10.1016/j.cyto.2026.157123","DOIUrl":"10.1016/j.cyto.2026.157123","url":null,"abstract":"<div><div>Vitiligo, a common autoimmune dermatosis, has a pathogenesis hypothesized to involve oxidative stress-induced immune-mediated melanocyte death. However, the role of oxidative stress in triggering autoimmunity during the early stages of vitiligo, along with its regulatory mechanisms and complex interactions, remains incompletely understood. Keratinocytes, as key initiating cells in vitiligo, secrete various chemokines, primarily C-X-C motif ligand 9 and 10 (CXCL9,10), under oxidative stress to recruit autoreactive immune cells targeting melanocytes. Hypoxia-inducible factor-1α (HIF-1α), a highly conserved transcription factor sensitive to oxidative stress, has been revealed to orchestrate cytokine expression and cellular immune functions. Based on this, the present study investigated the association between oxidative stress and HIF-1α in keratinocytes, and elucidated HIF-1α as a critical molecule bridging oxidative stress and autoimmunity in vitiligo. We initially observed significantly elevated HIF-1α levels in both the serum and depigmented lesions of vitiligo patients. Mechanistically, we demonstrates that HIF-1α serves as a potential biomarker associated with vitiligo progression, and through binding to the respective promoters of CXCL9 and CXCL10, regulates their expression and secretion in keratinocytes at the transcriptional level under oxidative stress, thus motivating peripheral blood mononuclear cells (PBMCs) migration to potential downstream melanocyte damage. HIF-1α activation further amplifies cellular oxidative stress damage in keratinocytes, collectively exacerbating the pathogenesis process of vitiligo. Our fundings suggest that the HIF-1α-CXCL9/10 pathway represents a promising therapeutic target for counteracting abnormal immune activation under oxidative stress in vitiligo.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"200 ","pages":"Article 157123"},"PeriodicalIF":3.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098713","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}

引用次数: 0

Cytokine profiling in oropouche fever highlights dissociation between systemic immunity and viral load 细胞因子谱在口腔热突出分离之间的全身免疫和病毒载量。

IF 3.7 3区医学

Cytokine Pub Date : 2026-03-01 Epub Date: 2026-01-20 DOI: 10.1016/j.cyto.2026.157119

Isabela Valim Sarmento , Julia Sthefany Zordan Nunes , Bruna Caetano Pimenta , Carlos Henrique Dettmann Fantecelle de Castro , Suwellen Sardinha Dias de Azevedo , Célio Geraldo Freire-de-Lima , Debora Decote Ricardo de Lima , Isabela Ribeiro Rodrigues , Anna Clara Gregório Có , Jaqueline Pegoretti Goulart , Eric Arrivabene Tavares , Edson Delatorre , Rodrigo Ribeiro Rodrigues , Luciana Polaco Covre , Daniel Cláudio Oliveira Gomes

{"title":"Cytokine profiling in oropouche fever highlights dissociation between systemic immunity and viral load","authors":"Isabela Valim Sarmento , Julia Sthefany Zordan Nunes , Bruna Caetano Pimenta , Carlos Henrique Dettmann Fantecelle de Castro , Suwellen Sardinha Dias de Azevedo , Célio Geraldo Freire-de-Lima , Debora Decote Ricardo de Lima , Isabela Ribeiro Rodrigues , Anna Clara Gregório Có , Jaqueline Pegoretti Goulart , Eric Arrivabene Tavares , Edson Delatorre , Rodrigo Ribeiro Rodrigues , Luciana Polaco Covre , Daniel Cláudio Oliveira Gomes","doi":"10.1016/j.cyto.2026.157119","DOIUrl":"10.1016/j.cyto.2026.157119","url":null,"abstract":"<div><div>Oropouche virus (OROV), a member of the <em>Peribunyaviridae</em> family, is an emerging arthropod-borne virus that has recently expanded across Brazilian states, establishing new transmission hotspots beyond the Amazon Basin. OROV infection causes an acute febrile illness with symptoms similar to those of other arboviruses. However, recent reports of fatal cases and vertical transmission leading to congenital anomalies have highlighted OROV as an emerging public health concern. In this study, we conducted an in-depth analysis of cytokine networks during acute Oropouche fever in patients with confirmed OROV infection. Using commercial cytokine panels, we quantified circulating inflammatory cytokines and chemokines and evaluated their correlations with viral load (inferred from cycle threshold values). OROV-infected patients exhibited a distinctive cytokine profile, with significant elevations in pro-inflammatory mediators including IL-18, monocyte chemoattractant protein-1, and tendency to increase IFN-α2, whereas IL-33 and TNF-α were reduced compared with healthy controls. Network analysis revealed tightly interconnected cytokines interactions during disease progression. Notably, inflammatory mediator levels did not correlate with viral load, indicating that systemic cytokine responses operate independently of viral replication kinetics. These findings reveal a unique inflammatory signature in OROV infection, suggesting specific pathogenic mechanisms important for understanding disease progression and developing therapeutic strategies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157119"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016816","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}

引用次数: 0

Elevated plasma Ang2/Tie2 ratio as a diagnostic and prognostic biomarker for sepsis in leukemia patients 血浆Ang2/Tie2比值升高作为白血病患者脓毒症的诊断和预后生物标志物

IF 3.7 3区医学

Cytokine Pub Date : 2026-03-01 Epub Date: 2026-01-13 DOI: 10.1016/j.cyto.2026.157118

Shu Yang , Rui Wang , Hao Li , Xingyong Chen , Jingbo Zhai , Mingdong Huang , Tianbin Chen , Meijuan Huang , Longguang Jiang

{"title":"Elevated plasma Ang2/Tie2 ratio as a diagnostic and prognostic biomarker for sepsis in leukemia patients","authors":"Shu Yang , Rui Wang , Hao Li , Xingyong Chen , Jingbo Zhai , Mingdong Huang , Tianbin Chen , Meijuan Huang , Longguang Jiang","doi":"10.1016/j.cyto.2026.157118","DOIUrl":"10.1016/j.cyto.2026.157118","url":null,"abstract":"<div><div>Dysregulation of the Ang-Tie pathway drives vascular leakage in sepsis. This study investigates plasma Ang-Tie axis components as sepsis biomarkers in leukemia through a retrospective cohort of 77 patients (36 with sepsis, 41 without sepsis). Septic patients exhibited significantly lower Ang1 (log<sub>10</sub>: 2.685 vs 3.143 pg/mL) and Tie2 (log<sub>10</sub>: 2.300 vs 2.800 pg/mL), but higher Ang2 (3.258 vs 2.841 pg/mL) than controls (<em>P</em> < 0.01). Critically, elevated Ang2/Ang1 (1.185 vs 0.917) and Ang2/Tie2 ratios (1.381 vs 0.995) strongly correlated with sepsis susceptibility. The Ang2/Tie2 ratio demonstrated superior diagnostic accuracy (AUC = 0.860, sensitivity = 86.1%, specificity = 80.5%) compared to routine biomarkers (D-dimer, procalcitonin). Strikingly, an Ang2/Tie2 ratio > 1.121 (Youden index) predicted a 3.5-fold increased mortality risk (95% CI: 1.51–8.25), independent of the leukemia subtype or treatment phase. These findings position the Ang2/Tie2 ratio as a dual diagnostic and pro gnostic biomarker for sepsis in leukemia patients, offering a mechanistic link between endothelial injury and poor outcomes. Our work bridges vascular biology and hematologic oncology, providing actionable insights for early intervention and targeted therapies to mitigate vascular leakage in high-risk populations</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157118"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974563","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}

引用次数: 0

Macrophage-mediated CXCL2 regulation of EPC homing promotes the progression of atherosclerosis 巨噬细胞介导的CXCL2调控EPC归巢促进动脉粥样硬化的进展。

IF 3.7 3区医学

Cytokine Pub Date : 2026-03-01 Epub Date: 2026-01-18 DOI: 10.1016/j.cyto.2026.157114

Jingting Mai , Runlu Sun , Wenhao Liu , Xinyu Hu, Ying Yang, Yangxin Chen, Jingfeng Wang

{"title":"Macrophage-mediated CXCL2 regulation of EPC homing promotes the progression of atherosclerosis","authors":"Jingting Mai , Runlu Sun , Wenhao Liu , Xinyu Hu, Ying Yang, Yangxin Chen, Jingfeng Wang","doi":"10.1016/j.cyto.2026.157114","DOIUrl":"10.1016/j.cyto.2026.157114","url":null,"abstract":"<div><div>Atherosclerosis is a chronic inflammatory disease driven by pathological angiogenesis and plaque instability. Herein, we investigated the role of macrophage-derived CXCL2 in mediating endothelial progenitor cell (EPC) homing during atherosclerosis progression. Using ApoE−/− mice on a high-fat diet and in vitro co-culture models, we found that infused EPCs exacerbated plaque burden, neovascularization, and matrix degradation. Macrophages were essential for EPC recruitment to plaques. Ox-LDL-stimulated macrophages enhanced EPC angiogenic functions, with transcriptome sequencing identifying CXCL2 as a key upregulated mediator. Functional experiments confirmed CXCL2's critical role. In vivo silencing of CXCL2 attenuated EPC homing, reduced plaque size and lipid accumulation, decreased neovascularization, and stabilized the plaque matrix. Our findings demonstrate that macrophages promote pathological angiogenesis and plaque progression via CXCL2, suggesting that targeting this chemokine could be a novel therapeutic strategy for stabilizing atherosclerotic plaques.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157114"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002744","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}

引用次数: 0

Molecular crosstalk between lncRNA H19, miR-29a, and JAK2/STAT3 signaling in alopecia areata: a preliminary study 斑秃中lncRNA H19、miR-29a和JAK2/STAT3信号传导之间的分子串扰：初步研究

IF 3.7 3区医学

Cytokine Pub Date : 2026-03-01 Epub Date: 2026-01-27 DOI: 10.1016/j.cyto.2026.157121

Aya A. Abd Elghany , Mostafa M. Kamel Eyada , Shymaa A. Maher , Noha M. Abd El-Fadeal , Lina M. Atef

{"title":"Molecular crosstalk between lncRNA H19, miR-29a, and JAK2/STAT3 signaling in alopecia areata: a preliminary study","authors":"Aya A. Abd Elghany , Mostafa M. Kamel Eyada , Shymaa A. Maher , Noha M. Abd El-Fadeal , Lina M. Atef","doi":"10.1016/j.cyto.2026.157121","DOIUrl":"10.1016/j.cyto.2026.157121","url":null,"abstract":"<div><h3>Background</h3><div>Alopecia areata (AA) is a common autoimmune disease which causes non-scarring patches of hair loss and has a 2% lifetime risk. Its chronic, recurrent nature makes treatment difficult. Potential roles of the JAK/STAT pathway, long non-coding RNAs (lncRNAs), & microRNAs (miRNAs) are highlighted by recent discoveries on the pathophysiology of alopecia areata (AA).</div></div><div><h3>Method</h3><div>This case-control study aimed to assess the role of lncRNA H19, miR-29a, and the JAK2/STAT3 pathway in alopecia areata (AA). We enrolled 29 patients and 30 healthy controls, collected venous blood from all participants, and quantified the expression of the target genes using real-time PCR.</div></div><div><h3>Results</h3><div>Both miR-29a and lncRNA H19 expression were found to be statistically significantly higher in alopecia areata (AA) patients than in the controls (<em>p</em> < 0.05). However, analysis revealed no significant change in the expression of either JAK2 or STAT3 in patients compared to controls.</div></div><div><h3>Conclusion</h3><div>This study identifies elevated levels of miR-29a and lncRNA H19 in the blood of alopecia areata patients, suggesting their potential role in disease pathophysiology. In contrast, the absence of significant change in JAK2/STAT3 mRNA points to a mechanism independent of transcriptional upregulation for this pathway. To validate these findings, larger, multi-center studies are needed to confirm these peripheral biomarkers in lesional scalp tissue and define the functional lncRNA H19/miR-29a mechanism.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157121"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074540","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}

引用次数: 0

The interleukin-1 receptor antagonist gene VNTR polymorphism confers a genetic contribution to the risk of immune thrombocytopenia purpura: A systematic review and meta-analysis 白细胞介素-1受体拮抗剂基因VNTR多态性与免疫性血小板减少性紫癜的遗传风险有关：一项系统综述和荟萃分析。

IF 3.7 3区医学

Cytokine Pub Date : 2026-03-01 Epub Date: 2026-01-12 DOI: 10.1016/j.cyto.2026.157112

Huifang Wei , Yuyang Xie , Qingyang Huai , Zixiao Hua , Xinyu Yang , Lingxi Chen , Youyi Kong , Wen Xue , Caiming Zhao , Shangshang Gao , Xiaoqin Yang

{"title":"The interleukin-1 receptor antagonist gene VNTR polymorphism confers a genetic contribution to the risk of immune thrombocytopenia purpura: A systematic review and meta-analysis","authors":"Huifang Wei , Yuyang Xie , Qingyang Huai , Zixiao Hua , Xinyu Yang , Lingxi Chen , Youyi Kong , Wen Xue , Caiming Zhao , Shangshang Gao , Xiaoqin Yang","doi":"10.1016/j.cyto.2026.157112","DOIUrl":"10.1016/j.cyto.2026.157112","url":null,"abstract":"<div><div>The purpose of this systematic review and meta-analysis was to summarize the existing evidence of the <em>IL1RN</em> variable number (usually two to six) of tandem repeat (VNTR) polymorphism in modulating the susceptibility to immune thrombocytopenia purpura (ITP), with the aim of clarifying its potential as a genetic marker for disease risk stratification. An extensive literature review was performed utilizing the Cochrane Library, NCBI PubMed, and Clarivate Web of Science databases, covering publications up to October 11, 2025. R language was employed to perform pooled estimation and present the results. The odds ratios and corresponding 95% confidence intervals were estimated to assess the strength of the effect. A total of 12 case-control studies comprising 770 ITP cases and 1424 controls were integrated for further synthetic analyses. Summary estimates in all genetic models suggested that the individuals carrying the variant with two repeats are more susceptible to this hematologic disorder. When stratified by geographic region, only the pooled estimates for Latin American and North African countries were statistically significant. No significant publication bias was evident. In conclusion, this meta-analysis indicated that the <em>IL1RN</em> VNTR polymorphism was significantly associated with ITP susceptibility, particularly in Latin American and North African populations.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157112"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964552","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}

引用次数: 0

Inflammatory imbalance in ambulance patients is associated with sepsis and septic shock 救护车病人的炎症失衡与败血症和感染性休克有关。

IF 3.7 3区医学

Cytokine Pub Date : 2026-03-01 Epub Date: 2026-01-10 DOI: 10.1016/j.cyto.2026.157107

Kedeye Tuerxun , Lisa Kurland , Eva Särndahl , Ulrika Wallgren , Daniel Eklund , Robert Kruse , X-HiDE Consortium

{"title":"Inflammatory imbalance in ambulance patients is associated with sepsis and septic shock","authors":"Kedeye Tuerxun , Lisa Kurland , Eva Särndahl , Ulrika Wallgren , Daniel Eklund , Robert Kruse , X-HiDE Consortium","doi":"10.1016/j.cyto.2026.157107","DOIUrl":"10.1016/j.cyto.2026.157107","url":null,"abstract":"<div><div>The host immune response in sepsis involves both pro- and anti-inflammatory mechanisms, with monocytes playing a central role in the process. We have previously identified an in vitro response profile of endotoxin (LPS) tolerant primary human monocytes, consisting of eight cytokines/chemokines as well as a set of five transcription factors. In the current study, we evaluated differences in expression levels of these investigated molecular markers across different patient groups (patients with or without infection, and with or without sepsis), and their association with clinical outcomes (septic shock and in-hospital mortality), among 809 ambulance patients. The results showed that patients with sepsis displayed the lowest <em>HLA-DRA</em> expression levels together with the lowest TNF/IL-10 ratio, while most other cytokine/chemokines and gene expressions were elevated. Higher levels of HGF, CCL8, CCL2, TNF and IL-10, as well as upregulation of <em>HIF1A</em> and <em>NFKBIA</em> were seen in septic patients with septic shock. The data suggests that the investigated immunological markers linked to immunosuppressed monocyte responses are associated with patients with sepsis and septic shock.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157107"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951106","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}

引用次数: 0

IL-6 trans-signaling activates the TGF-β pathway via soluble factors in difficult-to-treat rheumatoid arthritis joint fluid IL-6反式信号通过可溶性因子激活难治性类风湿关节炎关节液中TGF-β通路

IF 3.7 3区医学

Cytokine Pub Date : 2026-03-01 Epub Date: 2026-01-10 DOI: 10.1016/j.cyto.2026.157113

Yang Bei-bei , Liu Ji-zan , Rui Hong-bing , Xue Juan , Xiao Hua

{"title":"IL-6 trans-signaling activates the TGF-β pathway via soluble factors in difficult-to-treat rheumatoid arthritis joint fluid","authors":"Yang Bei-bei , Liu Ji-zan , Rui Hong-bing , Xue Juan , Xiao Hua","doi":"10.1016/j.cyto.2026.157113","DOIUrl":"10.1016/j.cyto.2026.157113","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the impact of joint fluid (JF) from difficult-to-treat (D2T)rheumatoid arthritis (RA) patients on joint inflammation.</div></div><div><h3>Methods</h3><div>We compared the clinical characteristics of D2T RA and non-D2T RA patients. Joint fluid samples from patients with various forms of chronic arthritis were analyzed. The activation of IL-6/STAT3 and TGF-β/SMAD3 pathways in normal Fibroblast-like synoviocytes (FLS) after exposure to D2T RA joint fluid was also evaluated, along with the effects of pathway inhibitors on cell proliferation, apoptosis, invasion, and migration.</div></div><div><h3>Results</h3><div>D2T RA joint fluid showed elevated levels of IL-6 and TGF-β1 compared to non-D2T RA, osteoarthritis, and ankylosing spondylitis samples. The IL-6/STAT3 pathway was directly activated in normal FLS upon exposure to D2T RA joint fluid, while the TGF-β/SMAD3 pathway was indirectly activated through IL-6 trans-signaling, resulting in increased proliferation, migration, invasion, and anti-apoptotic properties of FLS. The use of SMAD3 Inhibitory Selective 3 (SIS3) to block the TGF-β/SMAD3 pathway partially mitigated the effects of D2T RA joint fluid. Tocilizumab and the soluble glycoprotein 130 Fc fusion protein (sgp130Fc) successfully inhibited IL-6–associated pSMAD3 activation, highlighting a mediating role of IL-6.</div></div><div><h3>Conclusion</h3><div>The joint fluid milieu may contribute to persistent synovial activation in D2T RA, and highlights IL-6 trans-signaling as a potential therapeutic target in this context. In addition, timely aspiration of joint fluid from patients with D2T RA may help modulate the local inflammatory microenvironment and could represent a supportive strategy in disease management.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157113"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145923710","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}

引用次数: 0

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