Cytokine最新文献

{"title":"IRF4 exacerbates pulmonary inflammation in bronchopulmonary dysplasia mice model by regulating macrophage polarization and phagocytosis","authors":"Mengxu Yi ,&nbsp;Ying Zhu ,&nbsp;Mingyan Wang,&nbsp;Xingyu Mo,&nbsp;Yan Lu,&nbsp;Yu Qiao,&nbsp;Hongyan Lu","doi":"10.1016/j.cyto.2025.157069","DOIUrl":"10.1016/j.cyto.2025.157069","url":null,"abstract":"<div><div>This study investigates the critical function of interferon regulatory factor 4 (IRF4) during bronchopulmonary dysplasia (BPD) progression by regulating alveolar macrophages (AMs) polarization and phagocytic function. We developed IRF4 knockout mice using CRISPR/Cas9 technology and established an animal model for neonatal bronchopulmonary dysplasia (BPD) by hyperoxia exposure. Lung tissue pathology was analyzed by Hematoxylin and eosin staining (HE). The concentrations of TNF-α, IL-1β, IL-10, and TGF-β were ascertained by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to investigate M1/M2 macrophage polarization in bronchoalveolar lavage fluid (BALF) and lung tissue, while Western blotting and quantitative real-time PCR (qRT-PCR) were employed to detect IRF4, iNOS, and Arg-1 protein and mRNA expression. At cellular level, we silenced IRF4 in murine alveolar macrophage cell lines using IRF4 siRNA to investigate its effect on inflammatory cytokine secretion, polarization, and phagocytic function. To assess the effect of IRF4 on alveolar macrophage phagocytosis after hyperoxia, we utilized flow cytometry to ascertain the mean fluorescence intensity of engulfed fluorescent microspheres and fluorescence microscopy to quantify phagocytic cells. Hyperoxia-exposed mice showed markedly upregulated IRF4 expression, increased M1 macrophage and iNOS levels, and decreased M2 macrophages and Arg-1 expression. This cytokine shift was characterized by a marked upregulation of inflammatory factors such as TNF-α and IL-1β, accompanied by a notable decline in anti-inflammatory factors encompassing IL-10 and TGF-β, indicating an imbalance towards a pro-inflammatory state. IRF4 knockout or siRNA-mediated silencing attenuated the inflammatory response, promoting M2 macrophage differentiation while suppressing M1 differentiation. Phagocytic assays showed that hyperoxia impaired the phagocytic activity of AMs, while transfection of IRF4 siRNA restored the phagocytic activity of macrophage. IRF4 functions as a crucial regulator in the progression of hyperoxia-induced bronchopulmonary dysplasia, exerting its effects by influencing the polarization state and phagocytic function of alveolar macrophages. Deletion of IRF4 promotes an M2-dominant anti-inflammatory response, attenuates hyperoxia-induced inflammation, and increases the phagocytosis capacity of macrophages.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157069"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145464700","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 cytokines in immune cell-mediated multiple myeloma and the identification of therapeutic targets","authors":"Chao Wang,&nbsp;Yi Cai,&nbsp;Jie Jie","doi":"10.1016/j.cyto.2025.157075","DOIUrl":"10.1016/j.cyto.2025.157075","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple Myeloma (MM) disrupts immune function and causes multisystem damage. Despite treatment advances, the pathogenesis of relapse and resistance remain unclear. This study assesses the causal relationships between immune cell subtypes and MM using Mendelian randomization (MR), explores the mediating role of cytokines, and identifies potential therapeutic targets.</div></div><div><h3>Methods</h3><div>We employed a two-step MR approach to analyze mediating effects. Sensitivity analyses and Bayesian Weighted Mendelian Randomization (BWMR) were utilized to ensure the accuracy of results and to mitigate pleiotropy and heterogeneity. Additionally, Summary-data-based MR (SMR) was used to identify potential drug targets.</div></div><div><h3>Results</h3><div>The findings indicate causal effects of 20 immune cell subtypes and three cytokines on MM. SLAM mediated 9.16 % of the effect of CD4⁺ cells on MM. SMR analysis identified CD4⁺ and naive CD4⁺ cells as potential therapeutic targets for MM.</div></div><div><h3>Conclusions</h3><div>Through two-step MR and SMR analysis, this study reveals the mediating role of SLAM in the impact of CD4⁺ immune cells on MM and identifies two immune cell drug targets. Inhibiting the <em>KIT</em> gene may enhance the antitumor function of CD4⁺ T cells, offering new insights and potential strategies for immunotherapy of MM. These findings provide a theoretical basis for understanding the pathophysiology of MM and for developing novel immune-targeted therapies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157075"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561906","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":"2026-01-01","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":"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":"2026-01-01","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":"Dissecting the effect of blood colony-stimulating factors and receptors on Alzheimer's disease: the role of myeloid traits and inflammation","authors":"Xingzhi Guo ,&nbsp;Peng Tang ,&nbsp;Junchi He ,&nbsp;Rui Li","doi":"10.1016/j.cyto.2025.157072","DOIUrl":"10.1016/j.cyto.2025.157072","url":null,"abstract":"<div><h3>Background</h3><div>Research has suggested a potential link between colony-stimulating factors (CSFs) and Alzheimer's disease (AD), but the findings have been inconsistent, and the causal relationship remains uncertain.</div></div><div><h3>Methods</h3><div>We performed a Mendelian Randomization (MR) analysis to explore the association between blood levels of CSFs and their receptors with AD and its biomarkers. The study utilized summary-level data on blood levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, and their receptors from deCODE. Data on AD were sourced from the International Genomics of Alzheimer's Project (IGAP), UK Biobank (UKB), and FinnGen, while cerebrospinal fluid p-Tau and β-amyloid levels were from the largest GWAS currently available. Additional summary-level data on amyloid PET imaging and AD progression from ADNI and the Knight-ADRC were also included.</div></div><div><h3>Results</h3><div>Genetically predicted one standard deviation increase in blood G-CSF was associated with a higher risk of AD across three datasets (IGAP: OR = 1.35, 95 %CI = 1.15–1.57, <em>P</em> &lt; 0.001; IGAP+UKB: OR = 1.27, 95 %CI = 1.12–1.43, P &lt; 0.001; FinnGen: OR = 1.43, 95 %CI = 1.26–1.61, <em>P</em> &lt; 0.001), but not AD progression. Elevated blood G-CSF levels were inversely related to β-amyloid levels (β = −0.14, 95 %CI = -0.19 to −0.09, P &lt; 0.001) and positively associated with p-Tau levels (β = 0.08, 95 %CI = 0.03 to 0.14, <em>P</em> = 0.001) in cerebrospinal fluid. Furthermore, genetically predicted blood G-CSF levels were positively associated with amyloid PET imaging in the brain (β = 0.10, 95 % CI: 0.06 to 0.14, <em>P</em> &lt; 0.001). However, no significant associations were found between blood levels of other CSFs, and their receptors and AD risk. In contrast, there was little evidence supporting the impact of AD on CSFs levels. The multivariable MR analysis showed that the association between G-CSF and AD, along with its biomarkers, disappeared after adjusting for C-reactive protein levels, but not for neutrophil count.</div></div><div><h3>Conclusion</h3><div>These findings indicate a harmful role of G-CSF in the development of AD, primarily driven by inflammatory responses rather than neutrophil counts. Therefore, interventions targeting AD through CSFs, especially G-CSF, should be cautiously approached.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157072"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511339","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":"2026-01-01","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":"Characterizing the mechanisms underpinning interleukin-15Rα-mediated protection against sepsis and candidiasis","authors":"Jin Yang ,&nbsp;Banglao Xu ,&nbsp;Ju Cao ,&nbsp;Yuhan Liu ,&nbsp;Ling Tang ,&nbsp;Ping Zhao ,&nbsp;Sen Li ,&nbsp;Xin Li ,&nbsp;Jiayu Liu ,&nbsp;Renlin Yu ,&nbsp;Yin Tang ,&nbsp;Wang Tan ,&nbsp;Hao Ding ,&nbsp;Jin Li ,&nbsp;Yao Liu","doi":"10.1016/j.cyto.2025.157026","DOIUrl":"10.1016/j.cyto.2025.157026","url":null,"abstract":"<div><div>The interleukin (IL)-15Rα receptor has crucial, protective roles in sepsis and candidiasis via binding to its ligand, IL-15. However, the underlying mechanisms remain largely unexplored. In our study, we first confirmed the protective effects of IL-15 using clinical samples from patients with sepsis and candidiasis, and also in animal models with those conditions. We therapeutically administered IL-15 to IL-15Rα-deficient mice to elucidate the roles of IL-15Rα in sepsis and candidiasis treatment. Bacterial and fungal infections expedite mortality, caused organ damage, elevated the microbial burden in organs, and impaired macrophage recruitment, and subsequent microbial killing capacity. Notably, these adverse effects were alleviated via recombinant IL-15 supplementation, but this did not improve compromised conditions in IL-15Rα-deficient mice with sepsis. We show that IL-15Rα is required for protection against both bacterial and fungal sepsis, suggesting that this receptor could become a potential target for treating clinical sepsis and may hold significant clinical therapeutic value.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157026"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084751","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":"Role of macrophages reprogramming in pathogenesis of gestational diabetes mellitus","authors":"K.L. Milan,&nbsp;R. Adhi Shree,&nbsp;N. Nandana,&nbsp;R. Leela,&nbsp;K.M. Ramkumar","doi":"10.1016/j.cyto.2025.157041","DOIUrl":"10.1016/j.cyto.2025.157041","url":null,"abstract":"<div><div>Gestational diabetes mellitus (GDM) is a pregnancy-associated condition resulting from glucose intolerance affecting approximately 14 % of pregnant women worldwide and contributing to both maternal and neonatal complications. Macrophages, essential components of the innate immune system, exist in three main polarization states: M0 (resting), M1 (pro-inflammatory), and M2 (anti-inflammatory). In normal pregnancy, a proper balance between M1 and M2 phenotypes is critical for successful placentation and fetal development. Although this classification provides a useful framework, emerging evidence indicates that macrophages exist along a dynamic continuum of activation states with overlapping functional characteristics rather than discrete polarization categories. Recent studies further reveal that macrophage behavior in pregnancy involves context-dependent and plastic responses that cannot be fully captured by the M1/M2 paradigm alone. However, in GDM, hyperglycaemia significantly influences macrophage reprogramming toward a pro-inflammatory phenotype. The manuscript examines how dysregulated macrophage polarization contributes to insulin resistance, placental dysfunction, and adverse pregnancy outcomes. Emerging evidence suggests that hyperglycaemia induces trained immunity in macrophages, characterized by persistent expression of pro-inflammatory genes. In the GDM placenta, research indicates an altered M1/M2 ratio, though findings vary regarding specific polarization patterns. This review highlights promising therapeutic strategies targeting macrophage repolarization from M1 toward M2 phenotypes, including pharmacological approaches, RNA-based therapies, and <em>ex vivo</em> macrophage manipulation. Understanding macrophage reprogramming in GDM presents novel opportunities for interventions that may improve maternal-fetal outcomes and long-term metabolic health.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157041"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205069","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":"Therapeutic potential of IFIT2 in human diseases","authors":"Ewura-Esi Manful ,&nbsp;Francis Adu-Amankwaah ,&nbsp;Abhilasha Madhvi ,&nbsp;Kayla Bubb ,&nbsp;Ray-Dean Pietersen ,&nbsp;Bienyameen Baker","doi":"10.1016/j.cyto.2025.157049","DOIUrl":"10.1016/j.cyto.2025.157049","url":null,"abstract":"<div><div>The interferon-induced protein with tetratricopeptide repeats 2 (IFIT2) is a crucial member of the interferon-stimulated gene (ISG) family, widely acknowledged for its antiviral activity. IFIT2 functions primarily through AU-rich RNA binding, aiding in viral suppression by inhibiting protein translation and promoting apoptosis via mitochondrial pathways. While traditionally known for its role in antiviral defence, emerging research highlights its broader significance in cancer, bacterial and fungal infections, autoimmune diseases, neurological disorders, and metabolic and cardiovascular conditions. Notably, IFIT2 is the only IFIT family member with established tumour suppressor properties, demonstrating anti-proliferative effects in multiple cancers, including lung, renal, colorectal, breast, and gallbladder cancers.</div><div>Beyond oncology, IFIT2 has been implicated in the host response to <em>Mycobacterium tuberculosis</em>, <em>Plasmodium</em> spp., <em>Candida albicans</em>, and <em>Treponema pallidum</em>, where it modulates immune responses and infection outcomes. It is upregulated in several autoimmune diseases such as systemic lupus erythematosus, Sjögren's syndrome, and multiple sclerosis, suggesting its potential as a diagnostic and therapeutic biomarker. Furthermore, transcriptomic analyses have linked IFIT2 to disease progression and treatment response in conditions like diabetic ulcers, gestational diabetes, ischaemic cardiomyopathy, schizophrenia, and Alzheimer's disease.</div><div>This review thoroughly examines the molecular structure, regulatory mechanisms, and diverse roles of IFIT2 in human diseases. It addresses its interaction with key immune pathways, its ability to modulate apoptosis and inflammation, and its potential as a prognostic marker and therapeutic target. Although its mechanistic functions in numerous diseases remain only partly understood, IFIT2 emerges as a versatile immune effector with considerable translational promise. Further investigation into its biological roles will be crucial for utilising its therapeutic potential across infectious, inflammatory, metabolic, and neoplastic diseases.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157049"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218245","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":"Regulation of TREG/TH17 balance by NK cells pretreated with ESTRIOL and bacterial cells in multiple sclerosis","authors":"Irina Nekrasova ,&nbsp;Natalia Glebezdina ,&nbsp;Irina Maslennikova ,&nbsp;Irina Danchenko ,&nbsp;Sergei Shirshev","doi":"10.1016/j.cyto.2025.157038","DOIUrl":"10.1016/j.cyto.2025.157038","url":null,"abstract":"<div><div>We studied the influence of the pregnancy hormone estriol (E₃) and bacterial strains on the ability of NK cells to modulate levels of T regulatory (Treg) and IL-17-producing (Th17) lymphocytes from patients with multiple sclerosis (MS) and healthy donors. NK cell phenotype and cytokine production in co-cultures with CD4⁺ lymphocytes was also investigated after incubation with the hormone and bacterial cells. Treatment of NK cells with these factors stimulated Treg formation and inhibited Th17 development. Within 24 h, NK cell cytotoxicity and production of IL-2 and IFN-γ were inhibited, while IL-10 secretion increased. This was accompanied by a rise in IL-6 and TNF-α. After three days, NK cells showed increased IL-10 and decreased IL-17 expression. Notably, cells from MS patients were more sensitive to this regulatory influence than those from healthy donors.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157038"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218248","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}