Cytokine最新文献

{"title":"Association of the soluble form of the endothelial Tie2 receptor with organ failure and mortality in patients with sepsis and ARDS","authors":"Nicolas J. Wegmann ,&nbsp;Dorothea M. Heuberger ,&nbsp;Gabor Kadler ,&nbsp;Benjamin Seeliger ,&nbsp;Thorben Pape ,&nbsp;Klaus Stahl ,&nbsp;Mattia M. Müller ,&nbsp;Sascha David","doi":"10.1016/j.cyto.2025.157062","DOIUrl":"10.1016/j.cyto.2025.157062","url":null,"abstract":"<div><h3>Introduction</h3><div>Tie2 is an endothelial surface receptor critically involved in angiogenesis, cell-integrity, and survival. During inflammatory disorders such as sepsis and ARDS, the receptor is shed from the endothelial surface, contributing to a reduction of its protective downstream signaling ultimately contributing to endothelial permeability and thereby capillary leakage. This study investigates the association of the soluble form of Tie2 (sTie2), with multiorgan failure, requirement of dialysis and mortality.</div></div><div><h3>Methodology</h3><div>We conducted a biomarker study using serum samples from sepsis and/or ARDS patients admitted to the medical intensive care unit (ICU) of Hannover Medical School. sTie2 was quantified by Multiplex Luminex Assay in serum samples collected on the day of ICU admission. Correlations between sTie2 levels and baseline SOFA-score, duration of vasopressor therapy, and duration of mechanical ventilation were evaluated using Pearson's correlation coefficient. The Wilcoxon rank-sum test was employed to compare sTie2 levels between individuals with and without renal replacement therapy, as well as between survivors and non-survivors. Cox regression models were applied to assess the independent association of sTie2 with 28-day mortality.</div></div><div><h3>Results</h3><div>sTie2 levels showed an inverse correlation with the SOFA-score (<em>R</em> = −0.2, <em>p</em> = 0.003) and were lower in patients requiring renal replacement therapy (17.4 [12.25–22.48] vs. 21.35 [14.91–29.08] ng/ml, p = 0.003) and in non-survivors (14.54 [10.96–15.02] vs. 21.01 [15–28.12] ng/ml, <em>p</em> &lt; 0.001). No correlation was found between sTie2 and the number of days requiring vasopressor therapy or mechanical ventilation. Using multivariable cox regression, sTie2 was independently associated with mortality at 28-days (sTie2, log(ng/ml) – HR 0.35, 95% CI 0.21–0.57, <em>p</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>In this study of severely ill ICU patients, sTie2 was inversely related to severity of disease and to outcome. If the decrease in sTie2 is adaptive or maladaptive remains unclear but future investigations are required analysing the exact pathophysiological role of sTie2 to evaluate the biomarker as a potential target for the treatment of capillary leakage in patients with sepsis and/or ARDS.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157062"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375630","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":"Inhibiting TGF-β signaling pathway for disease therapy: challenges and opportunities","authors":"XiaoYan Gao ,&nbsp;XiuDan Li ,&nbsp;CongYing Zhang ,&nbsp;Jing Zhou ,&nbsp;Kai Gu ,&nbsp;XiaoQiang Liu ,&nbsp;ChunYing Bai","doi":"10.1016/j.cyto.2025.157048","DOIUrl":"10.1016/j.cyto.2025.157048","url":null,"abstract":"<div><div>Transforming growth factor (TGF)-β is a multifunctional cytokine expressed in nearly all human tissues and cell types. The TGF-β signaling pathway is essential for embryonic development, cell and tissue differentiation, and tissue homeostasis in adults. Aberrant regulation of this pathway is closely associated with various diseases, indicating that the TGF-β signaling pathway represents a promising target for therapeutic intervention. Notably, diseases linked to the disruption of the TGF-β signaling pathway include cancer, vascular disorders, wound healing complications, tissue fibrosis, and autoimmune diseases. The development and optimization of selective inhibitors targeting TGF-β could provide viable therapeutic options for the clinical treatment of these conditions. Consequently, targeting the cytokine TGF-β and its signaling pathway may offer a novel and promising treatment strategy for related diseases. This review summarizes recent studies on the role of TGF-β in the pathogenesis and treatment of associated diseases.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157048"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218246","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":"PAX9 and Col1A1 may regulate the progression of colon cancer through interactions with the TGF-β1/Smad pathway","authors":"Chao huang,&nbsp;Bingjun Liang,&nbsp;Weizeng Shen","doi":"10.1016/j.cyto.2025.157051","DOIUrl":"10.1016/j.cyto.2025.157051","url":null,"abstract":"<div><h3>Objective</h3><div>Transforming growth factor-β1 (TGF-β1) is widely involved in the progression of advanced cancer through the downstream Smad pathway, but the underlying mechanisms are still not fully understood. This project aimed to explore the relationship between key molecules of the TGF-β1/Smad pathway and the progression of colon cancer, as well as its upstream and downstream regulatory mechanisms.</div></div><div><h3>Methods</h3><div>Clinical data and related gene expression data of patients with colon cancer were retrieved from clinical databases and genomic libraries such as TCGA-COAD, GEO, and ENCODE. The expression levels of key molecules of the TGF-β1/Smad pathway (TGF-β1, TGF-β1 receptor, and SMAD2/3/4) in colon cancer/paracancerous tissue samples and their relationships with prognosis were analyzed. R packages and RStudio were used to analyze genes that were differentially expressed between colon cancer and normal tissues and the promoter regions bound by Smad2/3. JASPAR and GO/KEGG enrichment were used to predict upstream transcription factors and downstream regulatory genes of the TGF-β1/Smad pathway.</div></div><div><h3>Results</h3><div>A total of 459 patients with colon cancer were included in this study. Different TGF-β1 expression levels significantly affected the overall survival (OS) and disease-free survival (DFS) of patients with colon cancer (<em>P</em> &lt; 0.05). The expression of TGF-β1/Smad pathway molecules was significantly associated with the specific stage of cancer. A total of 954 genes had Smad2/3 binding sites in their promoter regions. The expression of the main transcription factor, paired box 9 (PAX9), that regulates the Smad2/3 pathway was generally higher in colon cancer tissues than in normal tissues. The expression of the transcription factor vitamin D (1,25- dihydroxyvitamin D3) receptor (VDR) was significantly different among different cancer types, especially in colon cancer, where its expression was significantly higher than that in normal tissues. Col1A1 expression was strongly correlated with that of TGF-β1 (<em>R</em> = 0.79, <em>P</em> &lt; 0.001). High expression of COL1A1 tended to reduce overall survival (<em>P</em> = 0.072), and the high-expression group had a 1.6 times lower risk of DFS than the low-expression group did (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>The TGF-β1/Smad pathway may regulate the progression and prognosis of colon cancer in conjunction with multiple upstream and downstream target genes (including PAX9, VDR, and Col1A1) and is related to cancer stage.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157051"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297852","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":"Rationalized combinatorial targeting of immune co-receptors leads to tumor regression","authors":"Saleha Nisar ,&nbsp;Prashant Chauhan ,&nbsp;Ashok Patidar ,&nbsp;Neelam Bodhale ,&nbsp;Uddipan Sarma ,&nbsp;Kalpana Pai ,&nbsp;Bhaskar Saha","doi":"10.1016/j.cyto.2025.157030","DOIUrl":"10.1016/j.cyto.2025.157030","url":null,"abstract":"<div><div>Different co-stimulatory and co-inhibitory molecules influence the dynamicity of an immune response. As their expression levels may collectively decide the amplitude and quality of an anti-tumor immune response, we proposed that the expression of these molecules would be dynamically modulated during a progressive tumor growth and that the study of their expression levels would guide fixing a combinatorial target for anti-tumor immunotherapy. Based on the kinetics of expression of 33 immune molecules within the tumor and draining lymph nodes during RM-1-induced progressive prostate tumor model in C57BL/6 mice, a three-phase combinatorial anti-tumor immunotherapy was designed. Phase- specific treatments with combinations of blocking antibodies against co-inhibitory receptors and agonistic antibodies against stimulatory receptors resulted in significant tumor regression and cytokines' expression, suggesting a strategic personalized anti-tumor immunotherapy with enhanced therapeutic efficacy, reduced toxicity and the risk of treatment failures.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157030"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-33 links inflammation and bone remodeling in experimental spondyloarthritis and human joint biopsies","authors":"Susana Aideé González-Chávez ,&nbsp;Mario Loya-Rivera ,&nbsp;Soumya Nair ,&nbsp;Rodrigo Prieto-Carrasco ,&nbsp;Eduardo Chaparro-Barrera ,&nbsp;Daniel Alberto Ruizesparza-Hinojos ,&nbsp;Sourav Roy ,&nbsp;César Pacheco-Tena","doi":"10.1016/j.cyto.2025.157031","DOIUrl":"10.1016/j.cyto.2025.157031","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the pathogenic role of IL-33 in spondyloarthritis (SpA) by analyzing its expression in both murine and human joint tissues and functionally assessing its impact on fibroblasts. The study evaluated synovial and entheseal biopsies from patients with SpA to explore the potential contribution of IL-33 to joint inflammation and tissue remodeling.</div></div><div><h3>Methods</h3><div>A spontaneous arthritis model (SpAD) in DBA/1 mice was used to assess IL-33 expression via histology, immunohistochemistry, transcriptomics, RT-qPCR, and western blot. Sacroiliac and tarsal biopsies from patients with SpA were also analyzed. Differential gene expression was checked, and pathway enrichment was performed using Ingenuity Pathway Analysis. Primary fibroblasts were isolated from the joints of the mice's front and rear limbs, transfected with siRNA targeting <em>Il33</em>, and evaluated by RT-qPCR and western blot for inflammatory (<em>Tnf</em>, <em>Nfkb</em>) and osteogenic (<em>Wnt2</em>, <em>Bmp2</em>) markers. Cell viability was assessed via MTT assay.</div></div><div><h3>Results</h3><div>IL-33 expression was elevated in murine and human SpA joints, with strong cartilage and subchondral bone localization. Transcriptomic data indicated upregulation of IL-33 signaling and enrichment of proinflammatory and fibrotic pathways. Silencing of <em>Il33</em> in fibroblasts significantly reduced IL-33 protein levels and decreased <em>Tnf</em> and <em>Wnt2</em> expression at both mRNA and protein levels, while <em>Bmp2</em> reduction was observed only at the transcript level.</div></div><div><h3>Conclusion</h3><div>IL-33 contributes to joint inflammation and may regulate osteogenic pathways implicated in pathological bone formation. These findings support IL-33 as a potential dual-action therapeutic target in SpA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157031"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079308","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":"Interferon tau in ruminant reproduction: Mechanisms of maternal recognition of pregnancy and implications for fertility enhancement","authors":"Iqra Batool ,&nbsp;Rehana Kausar ,&nbsp;Muhammad Shahbaz Qamar","doi":"10.1016/j.cyto.2025.157035","DOIUrl":"10.1016/j.cyto.2025.157035","url":null,"abstract":"<div><div>Low conception rates and early embryonic loss remain major constraints to reproductive efficiency in ruminants, particularly during the peri-implantation period. Maternal recognition of pregnancy (MRP) is largely mediated by interferon tau (IFNT), a ruminant-specific type I interferon secreted by the elongating conceptus. Initially recognized for its anti-luteolytic action through suppression of endometrial prostaglandin F2α, (PGF2α). IFNT is now known to exert systemic effects beyond the uterus. It induces interferon-stimulated genes in endometrial and peripheral immune cells, shaping an immune environment conducive to embryo tolerance. By modulating nuclear factor kappa B, signal transducer and activator of transcription 1, and interferon regulatory factors, IFNT downregulates pro-inflammatory cytokines such as tumor necrosis factor alpha and interferon gamma, while enhancing anti-inflammatory mediators including interleukin-10 and interleukin-4. This shift promotes a T-helper 2-dominant immune profile favorable for maternal–fetal tolerance. In addition, IFNT safeguards corpus luteum function by mitigating PGF2α-induced luteolysis and preserving vascular integrity. This occurs through downregulation of pro-regression genes such as transforming growth factor beta 1, endothelin 1, thrombospondin 1/2, and serpin family E member 1, alongside upregulation of angiogenic mediators such as platelet-derived growth factor subunit B. These actions stabilize the luteal microenvironment and ensure sustained progesterone secretion. This review highlights IFNT's pivotal role in MRP, emphasizing its endocrine and paracrine actions on luteal maintenance, ISG induction, and immune modulation. It also explores IFNT's potential as a biomarker for early pregnancy detection and its applications in reproductive biotechnology, with bovine data supported by ovine, murine, and human models for translational insights.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157035"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102496","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":"Neuregulin 4 attenuates osteoarthritis by decreasing macrophage M1 polarization through PI3K/AKT signaling","authors":"Chao Wang ,&nbsp;Jinjian Zheng ,&nbsp;Chengxin Li ,&nbsp;Puyi Sheng ,&nbsp;Linli Zheng","doi":"10.1016/j.cyto.2025.157036","DOIUrl":"10.1016/j.cyto.2025.157036","url":null,"abstract":"<div><div>Altered polarization of synovial macrophages has been identified as a key pathogenic factor in sustaining synovial inflammation and driving osteoarthritis(OA) progression.Neuregulin 4 (Nrg4) is widely involved in inflammatory diseases, such as hepatic inflammation, Crohn's disease, and atherosclerosis.In this study, we aimed to investigate the effects of Nrg4 on macrophages and synovitis and to elucidate the underlying mechanisms in the development of OA.We first evaluated the expression of Nrg4 and ErbB4 in OA patients and mouse model. The adeno-associated virus 5 vector carrying the Nrg4 gene (AAV5-Nrg4) was injected into the knee joints to overexpress Nrg4 in two OA models.In vitro, RAW264.7 macrophages and mouse bone marrow-derived macrophages (BMDMs) were cultured, induced to M1 macrophages, and then treated with Nrg4. RNA interference (RNAi) technique was used to inhibit the expression of the Nrg4 receptor ErbB4.The results demonstrated that Nrg4-ErbB4 signaling was decreased during OA. In vitro experiments showed that Nrg4 treatment significantly inhibited the M1 polarization of RAW264.7 cells and BMDMs and down-regulated the expression of pro-inflammatory genes.RNA sequencing (RNA-seq) analysis and related experiments revealed that Nrg4 regulated macrophage polarization mainly by inhibiting the PI3K/AKT signaling pathway.Intra-articular injection of AAV5-Nrg4 effectively alleviated joint damage and synovitis in collagenase-induced OA (CIOA) and destabilization of the medial meniscus(DMM)-induced OA models.</div><div>Nrg4-mediated suppression of M1 macrophage polarization in vivo was evidenced by attenuated iNOS concomitant with upregulated CD206 expression.In conclusion, our findings demonstrated that targeting Nrg4-ErbB4 axis may be a promising way to treat OA by reducing M1 macrophage polarization in synovial tissues.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157036"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102514","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":"Decreased serum VEGF, NRG1, and Neuropilin-1 levels in male patients with treatment-resistant schizophrenia: implications for VEGF as a protective factor","authors":"Lingshu Luan ,&nbsp;Liuyang Lu ,&nbsp;Li Xu ,&nbsp;Wanming Chen ,&nbsp;Qing Tian ,&nbsp;Xiaobin Zhang ,&nbsp;Haidong Yang","doi":"10.1016/j.cyto.2025.157056","DOIUrl":"10.1016/j.cyto.2025.157056","url":null,"abstract":"<div><h3>Background</h3><div>Vascular endothelial growth factor (VEGF), Neuregulin-1 (NRG1), and Neuropilin-1 are important neurotrophic factors involved in neurodevelopment, synaptic plasticity, and neuroprotection processes implicated in schizophrenia pathophysiology. This study aimed to investigate the expression patterns of these markers and their clinical implications in male patients with treatment-resistant schizophrenia (TRS) and chronically medicated schizophrenia (CMS).</div></div><div><h3>Methods</h3><div>In this cross-sectional study, serum levels of VEGF, NRG1β1, neuropilin-1, S100B, and S100A8 were measured using the Luminex liquid suspension chip technology in 31 TRS patients, 47 CMS patients, and 47 healthy controls. Psychiatric symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).</div></div><div><h3>Results</h3><div>VEGF levels were significantly lower in TRS versus controls (<em>P</em> &lt; 0.001), with no significant difference between TRS-CMS (<em>P</em> = 0.053) or CMS-controls (<em>P</em> = 0.051). NRG1β1 was significantly reduced in both TRS (<em>P</em> = 0.003) and CMS (P &lt; 0.001) groups compared to controls. Neuropilin-1 decreased significantly only in the TRS group versus controls (<em>P</em> = 0.029). No significant difference was observed in S100B and S100A8 levels across all groups (all <em>P</em> &gt; 0.05). Correlation analysis revealed a negative association between NRG1β1 levels and positive scores (<em>r</em> = −0.355, <em>P</em> = 0.014), and a significant positive correlation between VEGF levels and language function (<em>r</em> = 0.313, <em>P</em> = 0.032) in CMS patients. Additionally, VEGF demonstrated potential protective properties in TRS patients (B = -1.098, RR = 0.333, 95 %CI: 0.131–0.849, <em>P</em> = 0.021).</div></div><div><h3>Conclusion</h3><div>VEGF may serve as a protective factor against TRS, with its reduction possibly contributing to treatment resistance. The positive correlation between VEGF and language function suggests its role in cognitive processes, highlighting its potential as a biomarker in schizophrenia treatment.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157056"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290541","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":"Diagnostic potential of immune serum proteins in Osteosaropenia identified via proximity extension assay","authors":"Seok Woo Hong ,&nbsp;Jeong-Hwa Baek ,&nbsp;Kyung Jae Yoon ,&nbsp;Jeong-Hyun Kang","doi":"10.1016/j.cyto.2025.157054","DOIUrl":"10.1016/j.cyto.2025.157054","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcopenia, characterized by coexistence of osteoporosis and sarcopenia, is influenced by immunological dysfunction and systemic inflammation, however their specific roles remain unclear. This study aimed to investigate inflammation-related serum profiles in osteosarcopenia using the Proximity Extension Assay (PEA).</div></div><div><h3>Methods</h3><div>Overall, 50 participants with a history of falls and fractures were recruited and classified into three groups, controls, sarcopenia, and osteosarcopenia. Oseteosarcopenia was diagnosed in individuals with both functional sarcopenia and osteoporosis. Functional sarcopenia was diagnosed according to the Korean Working Group on Sarcopenia guidelines. Osteoporosis was defined as a T-score of the areal bone mineral density (aBMD) of the femoral neck ≤ −2.5. Serum inflammatory protein levels were quantified using the Olink® PEA inflammation panel, targeting 92 proteins.</div></div><div><h3>Results</h3><div>Twenty inflammation-related proteins were identified as differentially expressed proteins (DEPs), and 33 proteins showed significant correlations with clinical measures of muscle function or aBMD of the total hip, femoral neck or lumbar spine. Weighted Gene Co-Expression Network Analysis (WGCNA) identified 27 proteins with significant module membership and contribution to group separation. Notably, four proteins, including SLAMF1, OPG, FGF-23, and CSF-1 were DEPs, significant in WGCNA, and correlated with clinical variables. Principal component analysis and heatmap analyses revealed osteosacropenia as a distinct entity, differing from sarcopenia and controls. Bioinformatics suggested that T cell modulation and tumor necrosis factor binding capacity play significant roles in osteosarcopenia development.</div></div><div><h3>Conclusions</h3><div>Osteosarcopenia exhibited unique immune-related profiles distinct from those of sarcopenia and controls, emphasizing the potential role of inflammation and adaptive immunity in its pathogenesis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157054"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290578","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 dual role of IL-2 in systemic lupus erythematosus: balancing pro-inflammatory and anti-inflammatory effects","authors":"Hao Li ,&nbsp;Xiang Lin ,&nbsp;Jing He","doi":"10.1016/j.cyto.2025.157032","DOIUrl":"10.1016/j.cyto.2025.157032","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by chronic inflammation and immune dysregulation. Interleukin-2 (IL-2), a central cytokine in T-cell biology, plays a paradoxical role in SLE pathogenesis. On one hand, it promotes effector T cell and natural killer (NK) cell activity, thereby amplifying inflammation; on the other, it supports the expansion and function of regulatory T cells (Tregs), which are essential for maintaining immune tolerance. This dual functionality makes IL-2 a driver of autoimmunity and a potential immunotherapeutic target. This review outlines the molecular mechanisms underlying IL-2's pro- and anti-inflammatory roles in SLE, highlights the regulatory factors that shape its functional balance, such as receptor affinity, dosing, exposure duration, and the immune microenvironment, and discusses recent progress in low-dose IL-2therapy and engineered IL-2 variants. A comprehensive understanding of IL-2 signaling dynamics is essential for the designing development of precision therapies designed to restore immune homeostasis in SLE.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157032"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090928","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}