Cytokine最新文献

{"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":"2025-12-04","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":"Drug repurposing for cytokine storm: baricitinib, ciclesonide, and acalabrutinib modulate cytokine release in a translational in vitro lymphoblastoid cell line model","authors":"Luka Hiti,&nbsp;Tijana Markovič,&nbsp;Maša Kandušer,&nbsp;Irena Mlinarič-Raščan","doi":"10.1016/j.cyto.2025.157083","DOIUrl":"10.1016/j.cyto.2025.157083","url":null,"abstract":"<div><div>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 <em>in vitro</em> 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.</div><div>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.</div><div>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.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157083"},"PeriodicalIF":3.7,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145675966","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":"TREM-1: A potential prognostic marker in newborns with late-onset sepsis","authors":"Matheus Lucena Galhardo ,&nbsp;Maria Helena Baptista Nunes da Silva ,&nbsp;Fernanda Andrade Macaferri da Fonseca ,&nbsp;Fernanda de Toledo Gonçalves ,&nbsp;Isabela Firigato ,&nbsp;Isabela Silva-Avelar ,&nbsp;Caroline Borgato Guedes ,&nbsp;Jana Sicília Viotti de Oliveira ,&nbsp;Angela Midori Matuhara ,&nbsp;Werther Brunow de Carvalho ,&nbsp;Magda Carneiro-Sampaio ,&nbsp;Andreia Rangel-Santos ,&nbsp;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 &lt; 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}

{"title":"Natural killer cell-related gene signature predicts immune cell infiltration and improved survival in bladder cancer","authors":"Yinglong Huang ,&nbsp;Chen Gong ,&nbsp;Engui Yang ,&nbsp;Haichao Yuan ,&nbsp;Dihao Lv ,&nbsp;Chadanfeng Yang ,&nbsp;Wujie Chen ,&nbsp;Qingyu Wan ,&nbsp;Zhiyong Tan ,&nbsp;Haifeng Wang ,&nbsp;Mingxia Ding ,&nbsp;Senmao Li","doi":"10.1016/j.cyto.2025.157084","DOIUrl":"10.1016/j.cyto.2025.157084","url":null,"abstract":"<div><h3>Background</h3><div>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).</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157084"},"PeriodicalIF":3.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666439","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":"2025-12-01","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}

{"title":"Ontogeny of plasma cytokine and chemokine concentrations across the first four months of human life in a Papua new Guinean cohort","authors":"Athena N. Nguyen ,&nbsp;Thomas S. Kouyate ,&nbsp;Rebecca Ford ,&nbsp;Geraldine Masiria ,&nbsp;Joe Jude ,&nbsp;Alec L. Plotkin ,&nbsp;Oludare A. Odumade ,&nbsp;Joann Diray-Arce ,&nbsp;Olubukola T. Idoko ,&nbsp;Rym Ben-Othman ,&nbsp;on behalf of EPIC-HIPC consortium,&nbsp;Beate Kampmann ,&nbsp;Tobias R. Kollmann ,&nbsp;Peter Richmond ,&nbsp;Ofer Levy ,&nbsp;Anita H.J. van den Biggelaar ,&nbsp;William Pomat ,&nbsp;Kinga K. Smolen","doi":"10.1016/j.cyto.2025.157076","DOIUrl":"10.1016/j.cyto.2025.157076","url":null,"abstract":"<div><div>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; <em>n</em> = 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.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157076"},"PeriodicalIF":3.7,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145652896","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":"Adding pieces to the puzzle: IL-33 contribution to fibrogenesis in chronic lung allograft dysfunction","authors":"B. Perea ,&nbsp;C. Gambini ,&nbsp;I. Paggi ,&nbsp;S. Biancucci ,&nbsp;S. Cattelan ,&nbsp;M. Genovese ,&nbsp;M. d'Alessandro ,&nbsp;P. Cameli ,&nbsp;E. Bargagli ,&nbsp;A. Dilroba ,&nbsp;T. Pianigiani ,&nbsp;L. Bergantini","doi":"10.1016/j.cyto.2025.157080","DOIUrl":"10.1016/j.cyto.2025.157080","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157080"},"PeriodicalIF":3.7,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145652925","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":"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]","authors":"Xueqing Fang ,&nbsp;Congling Su ,&nbsp;Yan Luo ,&nbsp;Kai Pan ,&nbsp;Jian Lin ,&nbsp;Youliang Song ,&nbsp;Yize Huang ,&nbsp;Xiaochun Hu ,&nbsp;Zhiyong Shen","doi":"10.1016/j.cyto.2025.157077","DOIUrl":"10.1016/j.cyto.2025.157077","url":null,"abstract":"","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157077"},"PeriodicalIF":3.7,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627329","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":"Dysregulated inflammatory cytokines in MSM living with HIV who exhibited suboptimal immune reconstitution despite antiretroviral therapy (ART)","authors":"Heping Zhao ,&nbsp;Fenqi Da ,&nbsp;Dan Luo ,&nbsp;Anping Feng ,&nbsp;Hao Wu ,&nbsp;Yanshan Cai ,&nbsp;Xuemei Ling ,&nbsp;Huachun Zou ,&nbsp;Linghua Li","doi":"10.1016/j.cyto.2025.157074","DOIUrl":"10.1016/j.cyto.2025.157074","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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 &lt;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).</div></div><div><h3>Results</h3><div>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 (<em>r</em> = −0.34) and CD4+/CD8+ T cell ratio (<em>r</em> = −0.29), respectively.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157074"},"PeriodicalIF":3.7,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614949","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":"Association of toll-like receptors polymorphisms with atopy and asthma symptoms in Latin American children","authors":"Emília Maria Medeiros de Andrade Belitardo ,&nbsp;Cintia Rodrigues Marques ,&nbsp;Thiago Magalhães da Silva ,&nbsp;Eduardo Santos Silva ,&nbsp;Eric Roberto Guimarães Rocha Aguiar ,&nbsp;Mauricio Lima Barreto ,&nbsp;Neuza Maria Alcântara-Neves ,&nbsp;Camila Alexandrina Figueiredo","doi":"10.1016/j.cyto.2025.157073","DOIUrl":"10.1016/j.cyto.2025.157073","url":null,"abstract":"<div><h3>Background</h3><div>Polymorphisms in TLRs genes have been implicated in the physiopathological mechanisms of atopy and asthma.</div></div><div><h3>Objective</h3><div>The aim of this study was to assess the association between polymorphisms on <em>TLRs</em> and atopy/asthma in a highly admixture population of children from Salvador, Bahia, Brazil.</div></div><div><h3>Methods</h3><div>Cross-sectional study. We analyzed 192 SNPs in TLRs genes (<em>TLR1</em>-<em>TLR9</em>) in 1187 children aged 4–11 years living in the urban periphery of Brazil. Bivariate analyses were performed to evaluate the association between <em>TLRs</em> SNPs and asthma syptoms, skin prick test (SPT), and specific IgE to aeroallergens (sIgE). In addition, polytomous logistic regression was used to assess the association between <em>TLRs</em> SNPs and asthma phenotypes, adjusting for sex, age, helminth infection and individual ancestry. Lastly, logistic regression was used to assess gene-environment interactions between <em>TLRs</em> SNPs and different infections in the risk of asthma and atopy.</div></div><div><h3>Results</h3><div>For SPT positivity the most significant associations were identified for rs4833095 in in <em>TLR1</em> (OR: 1.42; 95 % CI: 1.17–1.71; <em>p</em> = 0.00002) and rs1039559 in <em>TLR6</em> (OR: 1.40; CI: 1.15–1.70; <em>p</em> = 0.0009). For sIgE to aeroallergens significant associations were observed for rs5743810 in <em>TLR6</em> (OR: 1.43; 95 % CI: 1.13–1.81 <em>p</em> = 0.004), rs3853839 in <em>TLR7</em> (OR: 1.38; 95 % CI: 1.08–1.76; <em>p</em> = 0.009), and the rs5744139 was the most significantly associated in <em>TLR5</em> gene (OR: 2.0, 95 % CI: 1.17–3.41; <em>p</em> = 0.007). For asthma symptoms significant positive associations were observed for the rs4833095 in <em>TLR1</em> (OR: 1.32; 95 % CI: 1.07–1.62; <em>p</em> = 0.009) and rs2241097 in <em>TLR5</em> (OR: 1.36; 95 % CI: 1.08–1.73; p = 0.009). Furthermore, rs4833095 (OR: 1.38, 95 % CI: 1.03–1.83; <em>p</em> = 0.028) in <em>TLR1</em> and rs2241097 (OR: 1.45; 95 % CI: 1.06–2.00; <em>p</em> = 0.020) in <em>TLR5</em> were positively associated with non-atopic asthma, while rs1039559 (OR: 1.45; 95 % CI: 1.06–2.00; <em>p</em> = 0.036) and rs6531673 (OR: 1.48; 95 % IC: 1.08–2.02; <em>p</em> = 0.014) in <em>TLR6</em> were associated with increased risk for atopic asthma. Gene-environment interaction analyses further revealed that specific infections (e.g., <em>Toxoplasma gondii, HSV, H. pylori, HAV, EBV,</em> and helminths<em>)</em> significantly modified these associations.</div></div><div><h3>Conclusion</h3><div>The results suggest functional significance of polymorphisms on <em>TLR1</em> subfamily, <em>TLR5</em> and <em>TLR6</em> on atopy and asthma, as well as pathogens involved in gene-environment interaction could also play a role in the immunopathological mechanism of atopy and asthma in the studied population.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157073"},"PeriodicalIF":3.7,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569452","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}