Cytokine最新文献_第4页

Systemic immune inflammation index, systemic inflammatory response index and pan-immune inflammation value in the prediction of idiopathic late-onset fetal growth restriction 全身性免疫炎症指数、全身性炎症反应指数和泛免疫炎症在预测特发性迟发性胎儿生长受限中的价值

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-05 DOI: 10.1016/j.cyto.2025.157081

Murat Levent Dereli , Sadun Sucu , Dilara Sarıkaya Kurt , Ahmet Kurt , Fahri Burçin Fıratlıgil , Tuğba Ağbal , Ali Turhan Çağlar

Background

Fetal growth restriction (FGR) is a major pregnancy complication associated with stillbirth, perinatal morbidity, mortality and long-term consequences for the offspring. Therefore, its prediction, early detection and appropriate follow-up are essential components of prenatal care. In most cases, also referred to as late-onset idiopathic FGR (IL-FGR), symptoms appear after 34 weeks and the underlying pathology is unclear. Our aim was to investigate the relationship between altered inflammation and pathogenesis using inflammatory indices calculated from the complete blood count.

Methods

We conducted a retrospective case-control study in a large tertiary hospital between 2022 and 2023. Data from all participants at the time of screening for fetal aneuploidy and structural anomalies at 11–14 weeks were retrospectively reviewed and compared.

Results

A total of 106 eligible participants with IL-FGR and 106 women who experienced a healthy prenatal and perinatal period were included. Neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), pan-immune inflammation value (PIV) and SIRI/body-mass index (BMI) were significantly higher in the IL-FGR group (p < 0.001 for all). SIRI/BMI with a cut-off value of >76.3 × 10³ × kg/μL × m² (64 % sensitivity, 80 % specificity) showed the best discriminatory performance for IL-FGR prediction. Correlation analysis of gestational age-adjusted parameters with these indices showed a negative correlation with birthweight, suggesting that higher values of the inflammatory indices at the 11–14-week aneuploidy screening are associated with a greater likelihood of severe IL-FGR.

Conclusions

Our results suggest an association between high SII, SIRI, PIV and SIRI/BMI and an increased risk of future IL-FGR. SIRI/BMI may be an important component of regression models that could be used in the future as a screening tool for predicting FGR. However, our results require further validation by future studies to confirm the specific clinical implications of these indices.

胎儿生长受限（FGR）是一种主要的妊娠并发症，与死产、围产期发病率、死亡率和后代的长期后果有关。因此，其预测，早期发现和适当的随访是产前护理的重要组成部分。在大多数病例中，也被称为迟发性特发性FGR (IL-FGR)，症状在34周后出现，潜在病理尚不清楚。我们的目的是通过全血细胞计数计算炎症指数来研究炎症改变与发病机制之间的关系。方法于2022 - 2023年在某大型三级医院进行回顾性病例对照研究。所有参与者在11-14周进行胎儿非整倍体和结构异常筛查时的数据进行回顾性回顾和比较。结果共纳入106名IL-FGR患者和106名产前和围产期健康的妇女。中性粒细胞与淋巴细胞比率（NLR）、全身免疫炎症指数（SII）、全身炎症反应指数（SIRI）、泛免疫炎症值（PIV）和SIRI/体重指数（BMI）在IL-FGR组均显著升高（p < 0.001）。SIRI/BMI的临界值为76.3 × 103 × kg/μL × m2（敏感性64%，特异性80%），对IL-FGR的预测具有最佳的鉴别效果。孕龄调整参数与这些指标的相关性分析显示，这些指标与出生体重呈负相关，表明在11 - 14周非整倍体筛查时，炎症指标越高，发生严重IL-FGR的可能性越大。结论高SII、SIRI、PIV和SIRI/BMI与未来IL-FGR风险增加有关。SIRI/BMI可能是回归模型的一个重要组成部分，可以作为未来预测FGR的筛选工具。然而，我们的结果需要通过未来的研究进一步验证，以确认这些指标的具体临床意义。

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引用次数: 0

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 肿瘤坏死因子α启动子变异（G-308 a: rs1800629和C-857 T:rs1799724）与1型糖尿病有关：一项荟萃分析和试验序列分析

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-04 DOI: 10.1016/j.cyto.2025.157082

Shengnan Zhang, Zhenyu Li, Xiaodong Yang

Introduction

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.

Materials and methods

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.

Results

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.

Conclusions

Variations in the TNF-α promoter at positions G-308 A and C-857 T are linked to an increased risk of T1D.

肿瘤坏死因子-α (TNF-α)通过复杂的免疫和代谢途径与1型糖尿病相关，突出了其多方面的作用。遗传差异，特别是在TNF-α基因启动子区域，通过改变基因表达影响个体对1型糖尿病的易感性。许多研究已经在不同人群中检测了TNF-α多态性与1型糖尿病之间的联系，但结果不一致。本研究通过对现有研究的详细荟萃分析，探讨了TNF-α与1型糖尿病之间的关系。材料和方法本荟萃分析检测了TNF-α基因启动子区域的四个snp: G-238 A， G-308 A， C-587 T和T- 1031c。文献检索使用PubMed、ScienceDirect、b谷歌Scholar、Embase、Web of Science和Scopus进行。系统地回顾相关文献，并根据特定的纳入和排除标准选择符合条件的研究。分析使用综合元分析软件，版本4。结果24项病例对照研究适合探讨TNF-α多态性与T1D易感性之间的关系。遗传比较模型显示TNF-α G-308 A和C-857 T变异与T1D风险之间存在关联，敏感性分析证实了这些发现。试验序列分析进一步验证了TNF-α启动子变异（G-308 A和C-857 T）之间的遗传关系，并表明有足够的研究可用于结论性荟萃分析。相反，没有发现启动子多态性G-238 A和T-1031C与T1D发病有显著关联，TSA提示需要在不同人群中进一步研究。结论TNF-α启动子g - 308a和c - 857t位点的变异与T1D风险增加有关。

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引用次数: 0

Drug repurposing for cytokine storm: baricitinib, ciclesonide, and acalabrutinib modulate cytokine release in a translational in vitro lymphoblastoid cell line model 细胞因子风暴的药物再利用：巴西替尼、环来奈德和阿卡拉布替尼在体外淋巴母细胞样细胞系模型中调节细胞因子释放。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-03 DOI: 10.1016/j.cyto.2025.157083

Luka Hiti, Tijana Markovič, Maša Kandušer, Irena Mlinarič-Raščan

Cytokine storm, a life-threatening hyperinflammatory response seen in severe infections like COVID-19, autoimmune diseases, and certain therapies, remains difficult to treat due to limited approved therapeutics. To support preclinical drug development and repurposing in line with 3R principles, we present a novel in vitro model for screening of cytokine-modulating compounds. Herein, we demonstrate that lymphoblastoid cell lines (LCL cells), derived from healthy donors, provide a translationally relevant and phenotypically diverse platform for cytokine profiling and drug screening. Upon stimulation with PMA/ionomycin, LCL cells exhibited a robust secretion of pro-inflammatory (IL-6, IL-8, TNF-α) and anti-inflammatory (IL-10) cytokines, closely mirroring the cytokine profile of activated whole blood. Compared to established immune cell lines THP-1 and Jurkat, LCL cells showed broader cytokine responses and retained interindividual variability.

We validated the model for cytokine-modulating drug screening using two well-established immunosuppressants, dexamethasone and cyclosporin A. Dexamethasone reduced IL-6 by 21 %, IL-8 by 71 %, IL-12 by 68 %, TNF-α by 83 %, and increased IL-10 by 51 %. Cyclosporin A lowered IL-6 by 34 %, IL-8 by 69 %, IL-10 by 48 %, and TNF-α by 41 %. Subsequently, we tested a panel of clinically investigated COVID-19 therapies, selected based on a comprehensive literature review. Ciclesonide and acalabrutinib showed strong suppression of all measured cytokines by more than 60 %, while baricitinib, which has become a standard of care for severe COVID-19, reduced IL-6 by 70 %, IL-12 by 68 %, and TNF-α by 47 %, but had minimal effect on IL-8. Notably, LCL cells retained interindividual variability, as demonstrated by diverse cytokine as well as divergent NF-κB nuclear translocation responses, supporting the model's capacity to reveal real-world patient heterogeneity.

Collectively, our findings establish LCL cells as a reproducible, immunologically responsive, and patient-representative platform for cytokine storm research and high-content drug testing, providing both mechanistic insight and translational relevance.

细胞因子风暴是一种危及生命的高炎症反应，常见于COVID-19等严重感染、自身免疫性疾病和某些疗法中，由于批准的治疗方法有限，仍然难以治疗。为了支持临床前药物开发和再利用符合3R原则，我们提出了一种新的体外模型筛选细胞因子调节化合物。在此，我们证明来自健康供体的淋巴母细胞样细胞系（LCL细胞）为细胞因子分析和药物筛选提供了翻译相关和表型多样化的平台。在PMA/离子霉素刺激下，LCL细胞表现出强烈的促炎（IL-6、IL-8、TNF-α）和抗炎（IL-10）细胞因子的分泌，与活化的全血细胞因子谱密切相关。与已建立的免疫细胞系THP-1和Jurkat相比，LCL细胞表现出更广泛的细胞因子反应，并保留了个体间的可变性。我们使用两种成熟的免疫抑制剂地塞米松和环孢素a验证了细胞因子调节药物筛选模型，地塞米松使IL-6减少21%，IL-8减少71%，IL-12减少68%，TNF-α减少83%，IL-10增加51%。环孢素A降低IL-6 34%， IL-8 69%, IL-10 48%, TNF-α 41%。随后，我们测试了一组临床研究的COVID-19疗法，这些疗法是根据全面的文献综述选择的。环来奈德和阿卡拉布替尼对所有测量的细胞因子的抑制作用超过60%，而巴西替尼已成为严重COVID-19的标准治疗方案，可使IL-6降低70%，IL-12降低68%，TNF-α降低47%，但对IL-8的影响最小。值得注意的是，LCL细胞保留了个体间的可变性，不同的细胞因子和不同的NF-κB核易位反应证明了这一点，这支持了该模型揭示现实世界患者异质性的能力。总的来说，我们的研究结果建立了LCL细胞作为细胞因子风暴研究和高含量药物测试的可复制、免疫应答和患者代表平台，提供了机制见解和翻译相关性。

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引用次数: 0

TREM-1: A potential prognostic marker in newborns with late-onset sepsis TREM-1：迟发性脓毒症新生儿的潜在预后标志物。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-03 DOI: 10.1016/j.cyto.2025.157085

Matheus Lucena Galhardo , Maria Helena Baptista Nunes da Silva , Fernanda Andrade Macaferri da Fonseca , Fernanda de Toledo Gonçalves , Isabela Firigato , Isabela Silva-Avelar , Caroline Borgato Guedes , Jana Sicília Viotti de Oliveira , Angela Midori Matuhara , Werther Brunow de Carvalho , Magda Carneiro-Sampaio , Andreia Rangel-Santos , Patricia Palmeira

Background

Diagnosing late-onset neonatal sepsis (LOS) continues to be a complex task, highlighting the need for continued research to discover reliable biomarkers that can improve both diagnostic accuracy and prognostic evaluation. This experimental prospective cohort study aimed to assess the potential of TREM-1 as a diagnostic and prognostic marker for LOS.

Methods

This study included 121 newborns (NBs) distributed as follows: 84 blood samples from NBs with LOS, categorized into Gram-negative sepsis, Gram-positive sepsis, and culture-negative sepsis groups, along with 37 infection-free controls. sTREM-1 levels were measured using an immunoenzymatic assay on samples collected at diagnosis and on days 3 and 7 afterward, while TREM1 gene expression was assessed by RT-qPCR on the day of diagnosis.

Results

Despite not being a significant diagnostic tool, the univariate logistic regression indicated that high sTREM-1 levels were strongly associated with septic shock, in addition to thermal instability and male sex. The adjusted multivariate analysis confirmed that elevated sTREM-1 levels (OR = 3.85, p = 0.032), and male sex (OR = 5.67, p = 0.016) were significantly associated with septic shock. Gene expression analysis revealed reduced TREM1 gene expression in infected neonates relative to controls; however, patients who died showed significantly higher expression levels (p < 0.001), indicating its potential as a prognostic marker in neonatal sepsis.

Conclusion

sTREM-1 showed good accuracy as a predictor of severity in LOS. TREM1 high expression was associated with a worse prognosis in septic neonates. However, additional studies involving a larger number of individuals are necessary to validate the clinical utility of this biomarker in practice.

背景：诊断迟发性新生儿脓毒症（LOS）仍然是一项复杂的任务，强调需要继续研究发现可靠的生物标志物，以提高诊断准确性和预后评估。本实验前瞻性队列研究旨在评估TREM-1作为LOS诊断和预后标志物的潜力。方法：本研究纳入121例新生儿，分布如下：84例LOS新生儿血液样本，分为革兰氏阴性脓毒症组、革兰氏阳性脓毒症组和培养阴性脓毒症组，以及37例无感染对照组。在诊断时和诊断后第3天和第7天，采用免疫酶法检测TREM1水平，在诊断当天采用RT-qPCR评估TREM1基因表达。结果：尽管不是一个重要的诊断工具，单变量逻辑回归表明，除了热不稳定性和男性外，高sTREM-1水平与感染性休克密切相关。调整后的多因素分析证实，sTREM-1水平升高（OR = 3.85, p = 0.032）和男性（OR = 5.67, p = 0.016）与脓毒性休克显著相关。基因表达分析显示，与对照组相比，感染新生儿TREM1基因表达降低；然而，死亡患者的表达水平明显更高(p)。结论：sTREM-1作为LOS严重程度的预测因子具有良好的准确性。TREM1高表达与脓毒症新生儿预后较差相关。然而，需要更多的研究来验证这种生物标志物在实践中的临床应用。

{"title":"TREM-1: A potential prognostic marker in newborns with late-onset sepsis","authors":"Matheus Lucena Galhardo , Maria Helena Baptista Nunes da Silva , Fernanda Andrade Macaferri da Fonseca , Fernanda de Toledo Gonçalves , Isabela Firigato , Isabela Silva-Avelar , Caroline Borgato Guedes , Jana Sicília Viotti de Oliveira , Angela Midori Matuhara , Werther Brunow de Carvalho , Magda Carneiro-Sampaio , Andreia Rangel-Santos , Patricia Palmeira","doi":"10.1016/j.cyto.2025.157085","DOIUrl":"10.1016/j.cyto.2025.157085","url":null,"abstract":"<div><h3>Background</h3><div>Diagnosing late-onset neonatal sepsis (LOS) continues to be a complex task, highlighting the need for continued research to discover reliable biomarkers that can improve both diagnostic accuracy and prognostic evaluation. This experimental prospective cohort study aimed to assess the potential of TREM-1 as a diagnostic and prognostic marker for LOS.</div></div><div><h3>Methods</h3><div>This study included 121 newborns (NBs) distributed as follows: 84 blood samples from NBs with LOS, categorized into Gram-negative sepsis, Gram-positive sepsis, and culture-negative sepsis groups, along with 37 infection-free controls. sTREM-1 levels were measured using an immunoenzymatic assay on samples collected at diagnosis and on days 3 and 7 afterward, while <em>TREM1</em> gene expression was assessed by RT-qPCR on the day of diagnosis.</div></div><div><h3>Results</h3><div>Despite not being a significant diagnostic tool, the univariate logistic regression indicated that high sTREM-1 levels were strongly associated with septic shock, in addition to thermal instability and male sex. The adjusted multivariate analysis confirmed that elevated sTREM-1 levels (OR = 3.85, <em>p = 0.032</em>), and male sex (OR = 5.67, <em>p = 0.016</em>) were significantly associated with septic shock. Gene expression analysis revealed reduced <em>TREM1</em> gene expression in infected neonates relative to controls; however, patients who died showed significantly higher expression levels (<em>p < 0.001</em>), indicating its potential as a prognostic marker in neonatal sepsis.</div></div><div><h3>Conclusion</h3><div>sTREM-1 showed good accuracy as a predictor of severity in LOS. <em>TREM1</em> high expression was associated with a worse prognosis in septic neonates. However, additional studies involving a larger number of individuals are necessary to validate the clinical utility of this biomarker in practice.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157085"},"PeriodicalIF":3.7,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145675969","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

Natural killer cell-related gene signature predicts immune cell infiltration and improved survival in bladder cancer 自然杀伤细胞相关基因标记预测膀胱癌免疫细胞浸润和提高生存率。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-02 DOI: 10.1016/j.cyto.2025.157084

Yinglong Huang , Chen Gong , Engui Yang , Haichao Yuan , Dihao Lv , Chadanfeng Yang , Wujie Chen , Qingyu Wan , Zhiyong Tan , Haifeng Wang , Mingxia Ding , Senmao Li

Background

Natural killer (NK) cell-based therapies represent a promising immunotherapeutic approach for cancer treatment. This study aims to identify and evaluate the prognostic significance of NK cell-related genes in bladder cancer (BC).

Methods

Using RNA-seq data from The Cancer Genome Atlas (TCGA) BLCA cohort, an NK cell-related gene signature was constructed and validated via multivariate Cox regression. Functional enrichment analyses (GO and KEGG) were conducted to explore associated biological processes. Immune infiltration states were assessed using ESTIMATE and CIBERSORT algorithms. Immunohistochemistry (IHC) and multiplex immunofluorescence (mIF) were performed to validate key findings at the protein level.

Results

An eight-gene prognostic signature based on NK cell-related genes was established, enabling stratification of BC patients into high- and low-risk groups. Patients in the high-risk group exhibited significantly worse overall survival (OS) and progression-free survival (PFS). Multivariate analysis confirmed the signature's independence from other clinical variables. The signature was also correlated with distinct immune infiltration patterns, including CD8⁺ T cells, CD4⁺ activated memory T cells, follicular helper T cells, regulatory T cells, activated NK cells, activated dendritic cells, and M0/M2 macrophages. Notably, the key signature gene RAC3 was found to be highly expressed in a subset of tumors. This elevated RAC3 expression was associated with enhanced proliferation (increased Ki67) and reduced infiltration of CD8⁺ T cells and CD56⁺ NK cells, indicating an immunosuppressive microenvironment. Consistently, the TIDE score was significantly lower in the high-risk group, suggesting enhanced potential responsiveness to immunotherapy.

Conclusion

The NK cell-related gene signature serves as a robust prognostic biomarker and predictor of immunotherapeutic efficacy in BC. These findings provide new insights into BC biology and facilitate personalized immunotherapy strategies.

背景：自然杀伤（NK）细胞为基础的治疗是一种很有前途的癌症免疫治疗方法。本研究旨在鉴定和评价NK细胞相关基因在膀胱癌（BC）中的预后意义。方法：利用癌症基因组图谱（TCGA） BLCA队列的RNA-seq数据，构建NK细胞相关基因标记，并通过多变量Cox回归进行验证。通过功能富集分析（GO和KEGG）来探索相关的生物过程。使用ESTIMATE和CIBERSORT算法评估免疫浸润状态。通过免疫组织化学（IHC）和多重免疫荧光（mIF）在蛋白水平上验证关键发现。结果：建立了基于NK细胞相关基因的8基因预后标记，可以将BC患者分为高危组和低危组。高危组患者的总生存期（OS）和无进展生存期（PFS）明显较差。多变量分析证实了签名与其他临床变量的独立性。该特征还与不同的免疫浸润模式相关，包括CD8+ T细胞、CD4+活化记忆T细胞、滤泡辅助T细胞、调节性T细胞、活化NK细胞、活化树突状细胞和M0/M2巨噬细胞。值得注意的是，关键标志基因RAC3被发现在肿瘤亚群中高度表达。这种升高的RAC3表达与增殖增强（Ki67增加）和CD8+ T细胞和CD56+ NK细胞浸润减少有关，表明免疫抑制微环境。与此一致的是，高危组的TIDE评分明显较低，表明对免疫治疗的潜在反应性增强。结论：NK细胞相关基因标记可作为BC免疫治疗效果的可靠预后生物标志物和预测因子。这些发现为BC生物学提供了新的见解，并促进了个性化的免疫治疗策略。

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引用次数: 0

FOXC1 ameliorates the disease progression of psoriasis through transcriptional upregulation of SOCS3 FOXC1通过上调SOCS3的转录来改善银屑病的疾病进展。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-01 DOI: 10.1016/j.cyto.2025.157078

Ziyu Duan, Ke Sha, Lu Bian, Yujiao Sun

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.

牛皮癣是一种慢性炎症性皮肤病，叉头盒C1 （FOXC1）已被证明对炎症和氧化应激均有抑制作用。然而，FOXC1在银屑病中的确切作用和潜在机制尚未得到充分探讨和阐明。本研究采用咪喹莫特（IMQ）诱导小鼠实验性银屑病，并采用m5诱导角化细胞（HaCaT）检测FOXC1在银屑病中的作用。FOXC1在imq诱导的小鼠和m5处理的HaCat细胞中下调。过表达FOXC1后，imq诱导的小鼠牛皮癣样皮肤病变得到改善。具体而言，上调IMQ小鼠FOXC1可导致关键炎症细胞因子浓度降低，包括S100A8、S100A9、TNF-α、IL-1β、IL-6和IL-17 a，有效缓解炎症反应。此外，FOXC1过表达对银屑病小鼠皮损区氧化应激、ROS生成减少、MDA含量降低、SOD活性恢复有有益作用。在检测FOXC1对m5诱导的HaCaT细胞的影响时，也得到了类似的结果。进一步的研究表明，细胞因子信号传导3的抑制因子（SOCS3）可能参与了这一过程。在HaCaT细胞中发现FOXC1转录上调SOCS3的表达。在m5诱导的HaCaT细胞中，SOCS3的抑制逆转了FOXC1过表达的保护作用，上调了S100A8和S100A9的表达，提高了ROS水平。因此，我们的研究结果表明FOXC1的上调可以改善牛皮癣的疾病进展。

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引用次数: 0

Ontogeny of plasma cytokine and chemokine concentrations across the first four months of human life in a Papua new Guinean cohort 巴布亚新几内亚一群人生命最初四个月血浆细胞因子和趋化因子浓度的个体发生

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-11-30 DOI: 10.1016/j.cyto.2025.157076

Athena N. Nguyen , Thomas S. Kouyate , Rebecca Ford , Geraldine Masiria , Joe Jude , Alec L. Plotkin , Oludare A. Odumade , Joann Diray-Arce , Olubukola T. Idoko , Rym Ben-Othman , on behalf of EPIC-HIPC consortium, Beate Kampmann , Tobias R. Kollmann , Peter Richmond , Ofer Levy , Anita H.J. van den Biggelaar , William Pomat , Kinga K. Smolen

Dynamic molecular changes in early life follow a robust ontogeny as the infant immune system adapts to the demands of its new environment. Studies of plasma immunomodulatory cytokines and chemokines have previously demonstrated ontogenetic patterns of immune development across the first week of life. However, how plasma cytokine and chemokines concentrations evolve over the first 4 months of life remains unknown. In this study, we examined plasma cytokine and chemokine concentrations in a longitudinal cohort of infants in Papua New Guinea (Oceania; n = 87) across the first four months of life. Using a multiplex assay, concentration of 41 cytokines and chemokines in peripheral blood plasma samples collected at Day of Life (DOL) 0 (i.e., birth), −7, −30, and − 128 were measured. Several cytokines and chemokines that shape cellular immunity demonstrated a statistically significant increase in concentration over the first four months of life, including CXCL10 (5.5-fold), IFNγ (8.8-fold), and IL-2 (1.7-fold). In contrast, other cytokines and chemokines significantly diminished with age, including CCL2 (0.12-fold), CXCL8 (0.35-fold), IL-6 (0.38-fold), and TGFα (0.43-fold). Plasma cytokine and chemokine concentrations appeared to be minimally affected by demographic factors such as birth season, gestational age, sex, or maternal age. The patterns and directionality of these observations largely mirrored those reported in previous cohorts, suggesting universal patterns of plasma cytokine and chemokine trajectories in early life. Overall, understanding early life trajectories of plasma cytokines and chemokines provides insight into human immune development and supports future studies analyzing cytokine trajectories in relation to health and disease.

随着婴儿免疫系统适应新环境的需要，生命早期动态分子变化遵循稳健的个体发育。血浆免疫调节细胞因子和趋化因子的研究先前已经证明了生命第一周免疫发育的个体发生模式。然而，血浆细胞因子和趋化因子浓度在生命的前4个月如何演变仍然未知。在这项研究中，我们检测了巴布亚新几内亚（大洋洲；n = 87）婴儿出生后4个月的血浆细胞因子和趋化因子浓度。采用多重测定法，测定在出生日（DOL） 0（即出生）、-7、-30和- 128采集的外周血血浆样品中41种细胞因子和趋化因子的浓度。影响细胞免疫的几种细胞因子和趋化因子在出生后的前四个月的浓度有统计学意义上的显著增加，包括CXCL10（5.5倍）、IFNγ（8.8倍）和IL-2（1.7倍）。相比之下，其他细胞因子和趋化因子随着年龄的增长而显著减少，包括CCL2（0.12倍）、CXCL8（0.35倍）、IL-6（0.38倍）和TGFα（0.43倍）。血浆细胞因子和趋化因子浓度似乎不受出生季节、胎龄、性别或母亲年龄等人口统计学因素的影响。这些观察结果的模式和方向性在很大程度上反映了之前的队列报道，表明早期生命中血浆细胞因子和趋化因子轨迹的普遍模式。总的来说，了解血浆细胞因子和趋化因子的早期生命轨迹有助于了解人类免疫发育，并支持未来研究分析与健康和疾病相关的细胞因子轨迹。

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引用次数: 0

Adding pieces to the puzzle: IL-33 contribution to fibrogenesis in chronic lung allograft dysfunction 增加拼图：IL-33在慢性同种异体肺移植功能障碍中的纤维化贡献。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-11-30 DOI: 10.1016/j.cyto.2025.157080

B. Perea , C. Gambini , I. Paggi , S. Biancucci , S. Cattelan , M. Genovese , M. d'Alessandro , P. Cameli , E. Bargagli , A. Dilroba , T. Pianigiani , L. Bergantini

Interleukin-33 (IL-33) is a pleiotropic, chromatin-binding cytokine primarily expressed by non-hematopoietic cells, including endothelial cells, fibroblasts and bronchial epithelial cells. It participates in various respiratory diseases, such as acute and chronic inflammatory diseases, viral infections, lung cancer and COPD, and is known to mediate asthma and allergic conditions. IL-33 plays a dual and context-dependent role, contributing to tissue homeostasis and immune regulation under physiological conditions, while promoting inflammation and fibrosis in pathological contexts. Its signalling is mediated by the ST2 receptor, which exists in two forms: the membrane-bound ST2L that activates immune responses, and the soluble decoy receptor sST2 that negatively regulates IL-33 activity. Over the past decade, medical research has cast a spotlight on the widespread contribution of IL-33 biology not only to inflammation but also to the development of fibrosis and lung transplant rejection. A comprehensive overview of the interactions between rejection following lung transplant and IL-33 signalling is lacking. In this review, we summarize the most recent literature regarding the IL-33 in relation to chronic lung allograft dysfunction (CLAD) and acute rejection. We also discuss the potential contribution of microbial and environmental stimuli in shaping IL-33-driven type 2 and autophagic responses in the lung transplant microenvironment. Recent findings regarding therapeutic implications of IL-33 were also reported.

白细胞介素-33 （IL-33）是一种多效性的染色质结合细胞因子，主要由非造血细胞表达，包括内皮细胞、成纤维细胞和支气管上皮细胞。它参与各种呼吸系统疾病，如急慢性炎症性疾病、病毒感染、肺癌和慢性阻塞性肺病，并介导哮喘和过敏性疾病。IL-33具有双重和情境依赖性作用，在生理条件下参与组织稳态和免疫调节，而在病理条件下促进炎症和纤维化。其信号传导由ST2受体介导，其存在两种形式：激活免疫应答的膜结合ST2L和负性调节IL-33活性的可溶性诱饵受体sST2。在过去的十年里，医学研究已经把焦点放在IL-33生物学的广泛贡献上，不仅在炎症中，而且在纤维化和肺移植排斥反应的发展中。对肺移植后排斥反应与IL-33信号传导之间的相互作用缺乏全面的概述。在这篇综述中，我们总结了最近关于IL-33与慢性同种异体肺移植功能障碍（CLAD）和急性排斥反应的关系的文献。我们还讨论了微生物和环境刺激在肺移植微环境中形成il -33驱动的2型和自噬反应中的潜在贡献。最近关于IL-33治疗意义的发现也被报道。

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引用次数: 0

Corrigendum to “Risk factors associated with short-term mortality in patients with candidemia and the predictive value of serum cytokine level” [Cytokine 185 (2025) 156803] 念珠菌病患者短期死亡率的相关危险因素及血清细胞因子水平的预测价值[细胞因子185(2025)156803]的勘误表。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-11-28 DOI: 10.1016/j.cyto.2025.157077

Xueqing Fang , Congling Su , Yan Luo , Kai Pan , Jian Lin , Youliang Song , Yize Huang , Xiaochun Hu , Zhiyong Shen

引用次数: 0

Dysregulated inflammatory cytokines in MSM living with HIV who exhibited suboptimal immune reconstitution despite antiretroviral therapy (ART) 感染艾滋病病毒的男男性行为者在接受抗逆转录病毒治疗后仍表现出不理想的免疫重建

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-11-25 DOI: 10.1016/j.cyto.2025.157074

Heping Zhao , Fenqi Da , Dan Luo , Anping Feng , Hao Wu , Yanshan Cai , Xuemei Ling , Huachun Zou , Linghua Li

Introduction

The relationship between serum cytokine levels and immunologic non-response in people living with HIV (PLWH) receiving antiretroviral therapy (ART) remains inadequately characterized. This study aimed to comprehensively characterize the serum cytokine profiles of men who have sex with men (MSM) living with HIV who exhibited different immunologic responses to ART.

Methods

We recruited MSM living with HIV and HIV-uninfected MSM (healthy controls, HC) in Guangzhou between June 1 to October 31, 2021. MSM living with HIV were classified as poor immunological responders (PIR, CD4+ T cell count <350 cells/μL) and good immunological responders (GIR, ≥ 350 cells/μL) after more than 24 months of ART. Blood samples were collected, and serum cytokines were quantified using Olink multiplex proximity extension assay (PEA).

Results

A total of 134 MSM were enrolled, including 44 HC, 52 GIR, and 38 PIR. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed significant difference in the PI3K-AKT signaling pathways between GIR and PIR. Six candidate cytokine markers (PD-L1, FGF-19, CD244, CD8α, 4E-BP1, and CASP-8) were identified by least absolute shrinkage and selection operator (LASSO) regression for the construction of diagnostic models. The corresponding area under the curve (AUC) based on these six candidate markers was 0.844 (95 %CI: 0.647–1.000) in the support vector machine (SVM) model. Notably, PD-L1 and FGF-19 were identified as the top2 important cytokines for distinguishing between GIR and PIR based on LASSO regression, random forest (RF), and SVM analyses. Furthermore, PD-L1 and FGF-19 levels were negatively correlated with CD4+ T cell count (r = −0.34) and CD4+/CD8+ T cell ratio (r = −0.29), respectively.

Conclusions

Distinct serum cytokine profiles were observed among PLWH with divergent immunologic responses, offering novel insights into the pathogenesis of immunologic non-response and identifying serum cytokines as promising therapeutic targets.

在接受抗逆转录病毒治疗（ART）的HIV感染者（PLWH）中，血清细胞因子水平与免疫无反应之间的关系仍然没有充分的表征。本研究旨在全面表征对ART表现出不同免疫反应的男男性行为者（MSM）的血清细胞因子谱。方法于2021年6月1日至10月31日在广州招募HIV感染者和未感染HIV的MSM（健康对照，HC）。艾滋病毒感染者在接受抗逆转录病毒治疗24个月以上后，分为不良免疫应答（PIR， CD4+ T细胞计数≥350细胞/μL）和良好免疫应答（GIR，≥350细胞/μL）。采集血样，用Olink多重邻近延伸法（PEA）定量测定血清细胞因子。结果共纳入134例MSM，其中HC 44例，GIR 52例，PIR 38例。京都基因与基因组百科（KEGG）通路富集分析显示，GIR和PIR之间PI3K-AKT信号通路存在显著差异。6种候选细胞因子标志物（PD-L1、FGF-19、CD244、CD8α、4E-BP1和CASP-8）通过最小绝对收缩和选择算子（LASSO）回归确定，用于构建诊断模型。在支持向量机（SVM）模型中，这6个候选标记对应的曲线下面积（AUC）为0.844 （95% CI: 0.647-1.000）。值得注意的是，基于LASSO回归、随机森林（RF）和SVM分析，PD-L1和FGF-19被确定为区分GIR和PIR的前2个重要细胞因子。此外，PD-L1和FGF-19水平分别与CD4+ T细胞计数（r = - 0.34）和CD4+/CD8+ T细胞比值（r = - 0.29）呈负相关。结论在不同免疫应答的PLWH中观察到不同的血清细胞因子谱，为免疫无应答的发病机制提供了新的见解，并确定血清细胞因子是有希望的治疗靶点。

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引用次数: 0