Immunobiology最新文献

{"title":"USP14 promotes osteoarthritis progression by deubiquitinating FZD8 to activate the Wnt/β-catenin signaling pathway","authors":"Xiaochao Chen,&nbsp;Tiancheng Ma,&nbsp;Yongfeng Chen,&nbsp;Qiang Sun,&nbsp;Huayi Wang,&nbsp;Yuanrui Wang","doi":"10.1016/j.imbio.2025.152905","DOIUrl":"10.1016/j.imbio.2025.152905","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA) is a chronic degenerative disease and associated with multiple pathogenic factors, such as old age, heredity, obesity, mechanical damage and inflammatory gene mutation. In this study, we aimed to explore the functions of ubiquitin specific peptidase 14 (USP14) in OA development.</div></div><div><h3>Methods</h3><div>The <em>in vitro</em> model of OA was constructed by stimulating chondrocytes with IL-1β. qRT-PCR and western blot assays were used for gene expression. MTT assay and EdU assay were manipulated to evaluate cell proliferation. Flow cytometry analysis was conducted for cell apoptosis. ELISA kits were utilized to determine the concentrations of inflammatory cytokines. Co-immunoprecipitation (Co-IP) assay and GST pull-down assay were manipulated to estimate the interaction between USP14 and Frizzled 8 (FZD8). Ubiquitination assay was used to evaluate the deubiquitination of FZD8.</div></div><div><h3>Results</h3><div>USP14 was highly expression in OA cartilage tissues and IL-1β-triggered chondrocytes. USP14 silencing aggravated the proliferation and repressed the apoptosis, inflammation and extracellular matrix (ECM) degradation of IL-1β-treated chondrocytes. USP14 could interact with FZD8 and regulate FZD8 expression through FZD8 deubiquitination. Moreover, FZD8 overexpression alleviated the effects of UPS14 silencing on IL-1β-treated chondrocyte proliferation, apoptosis, inflammation and ECM degradation. Additionally, USP14 knockdown inhibited Wnt/β-catenin signal pathway via the deubiquitination of FZD8.</div></div><div><h3>Conclusion</h3><div>USP14 repressed IL-1β-treated chondrocyte proliferation and promoted apoptosis, inflammation and ECM degradation by regulating FZD8 expression and Wnt/β-catenin signal pathway.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152905"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CH25H/25-HC promotes pulmonary fibrosis via AMPK/STAT6 pathway-dependent M2 macrophage polarization in COPD","authors":"Ying Li,&nbsp;Guangzhi Xiao,&nbsp;Xianghui Fu,&nbsp;Xing Luo,&nbsp;Fengfan Yang,&nbsp;Yadan Li,&nbsp;Zhaohui Zheng","doi":"10.1016/j.imbio.2025.152908","DOIUrl":"10.1016/j.imbio.2025.152908","url":null,"abstract":"<div><h3>Objective</h3><div>Chronic obstructive pulmonary disease (COPD) is intricately linked to pulmonary fibrosis, yet the underlying mechanisms remain unclear. This study investigates whether CH25H/25-hydroxycholesterol (25-HC) promotes pulmonary fibrosis in COPD by modulating AMPK/STAT6-dependent M2 macrophage polarization.</div></div><div><h3>Methods</h3><div>Using GEO datasets and a cigarette smoke-induced COPD mouse model, we analyzed CH25H expression and fibrotic pathology. CH25H was silenced via adeno-associated virus (AAV)-delivered shRNA. Histopathology, flow cytometry, qPCR, and Western blotting assessed fibrosis, macrophage polarization (M1/M2), and AMPK/STAT6 pathway activity. Bone marrow-derived macrophages (BMDMs) were employed to validate polarization mechanisms. The role of the AMPK/STAT6 pathway was investigated using the specific activator.</div></div><div><h3>Results</h3><div>Analysis of the GEO database and experimental verification showed significantly increased CH25H expression in both lung tissues and macrophages from COPD mice. CH25H knockdown alleviated alveolar damage, airway remodeling, and pulmonary fibrosis in COPD mice, evidenced by reduced expression of fibrosis-related proteins, improved lung function, and attenuated inflammatory responses. Moreover, CH25H knockdown inhibited M2 macrophage polarization and decreased the proportion of M2-type macrophages. Importantly, decreased levels of 25-HC following CH25H knockdown were asso ciated with suppressed activation of the AMPK/STAT6 pathway. Rescue experiments demonstrated that the protective effects of CH25H knockdown could be reversed by adding the AMPKα activator GSK621.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that CH25H/25-HC exacerbates COPD-associated pulmonary fibrosis by promoting AMPK/STAT6-dependent M2 macrophage polarization. Targeting CH25H may represent a novel therapeutic strategy for mitigating fibrosis in COPD.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152908"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA and TCR repertoire analysis identify markers of virus-specific T cells","authors":"Byung-Kwan Jeong ,&nbsp;Young-Ae Kim ,&nbsp;Jung-Wook Park ,&nbsp;Baknoon Ham ,&nbsp;Jihyeong Kim ,&nbsp;Gyungyub Gong ,&nbsp;Chae Lyul Lim ,&nbsp;Hee Jin Lee","doi":"10.1016/j.imbio.2025.152904","DOIUrl":"10.1016/j.imbio.2025.152904","url":null,"abstract":"<div><div>Adoptive cell therapy (ACT) is a promising method for treating cancer and viral infections. Identifying antigen-specific T cells (ASTs) is critical to ACT. We investigated biomarkers for identifying ASTs. Peripheral blood mononuclear cells from healthy donors underwent staining with carboxyfluorescein succinimidyl ester (CFSE) to detect proliferating ASTs. Following exposure to CMV pp65 peptide and interleukin-2 for T-cell expansion, CD3⁺/CD8⁺ T cells were isolated at varying time points, revealing distinct populations. TCR repertoire analysis unveiled nine major clones in CFSE⁻/CD3⁺/CD8⁺ T cells on day 7, constituting 93.9 % of total cells. Contrarily, CFSE⁺/CD3⁺/CD8⁺ T cells exhibited minimal overlap with major TCR clones. Combined single-cell RNA-seq analyses highlighted upregulated genes associated with cell cycle proliferation and T-cell cytotoxicity. Engineered T cells expressing dominant clones effectively engaged CMV pp65 peptide, triggering T-cell activation and interferon-γ production. A set of seven upregulated genes in CFSE⁻/CD3⁺/CD8⁺ T cells on day 7, indicative of proliferating ASTs, was used to identify antigen-specific CD3⁺/CD8⁺ T cells on days 2–3, exhibiting 93.52 % accuracy. These markers predicted CFSE⁻/CD3⁺/CD8⁺ T cells with dominant TCR clones following exposure to EBV peptide with 74.59 % accuracy. In conclusion, we identified new markers facilitating the early isolation of viral antigen-responsive T cells.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152904"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpretable Machine Learning reveals the Role of PANoptosis in the Diagnosis and Subtyping of NAFLD","authors":"Feng Tian ,&nbsp;Yuqi Zhao ,&nbsp;Xinyang He ,&nbsp;Yu Zhang ,&nbsp;Minxuan Hu ,&nbsp;Yiwei Liang ,&nbsp;Ziyou Tian ,&nbsp;Yaxian Gao ,&nbsp;Yongwei Wang","doi":"10.1016/j.imbio.2025.152909","DOIUrl":"10.1016/j.imbio.2025.152909","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) is a global health challenge characterized by complex pathogenesis and limited therapeutic options. Emerging evidence highlights PANoptosis—a coordinated interplay of pyroptosis, apoptosis, and necroptosis—as a critical driver of metabolic and immune dysregulation in NAFLD. Here, we integrated multiple datasets and interpretable machine learning to unravel the role of PANoptosis in NAFLD diagnosis, subtyping, and immune microenvironment remodeling. By intersecting differentially expressed genes and PANoptosis-related genes, we identified 9 hub genes (e.g., TRADD, CASP6, TNFRSF1A and TNFAIP3) and constructed a robust diagnostic model (AUC = 0.976) validated via SHAP analysis and nomogram. Unsupervised consensus clustering stratified NAFLD patients into two PANoptosis-driven subtypes (C1/C2 and CA/CB), revealing distinct immune cell infiltration patterns and pathway activation. Single-cell sequencing further localized hub genes to immune cells and revealed their cell communication, implicating their roles in the progression of NAFLD. Molecular docking studies identified fostamatinib and minocycline as potential therapeutic candidates, while pan-cancer analysis revealed that TNFRSF1A overexpression is associated with poor prognosis across multiple cancer types. This study enhances the understanding of PANoptosis as a crucial diagnostic and therapeutic target in NAFLD, providing novel insights into immune-mediated pathogenesis and paving the way for treatment strategies.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152909"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HMGB1 regulates the activation of dendritic cells and CD4+ T cell responses through the modulation of autophagy in bleomycin-induced pulmonary fibrosis","authors":"Xiuhua Liu ,&nbsp;Xinghui Song ,&nbsp;Guangting Li ,&nbsp;Yuping Zhang ,&nbsp;Nina Liu ,&nbsp;Kaijiang Tang ,&nbsp;Hongyan Du ,&nbsp;Ligang Jie","doi":"10.1016/j.imbio.2025.152906","DOIUrl":"10.1016/j.imbio.2025.152906","url":null,"abstract":"<div><h3>Background</h3><div>The role of HMGB1 in inflammation and autophagy has garnered increasing attention; however, its impact on the activation of dendritic cells (DCs) and autophagy remains unclear. This study aims to explore the effects of HMGB1 on DC activation, autophagy, and its influence on CD4+ T cell responses in a bleomycin-induced pulmonary fibrosis (PF) mouse model.</div></div><div><h3>Methods</h3><div>Thirty mice were randomly divided into control and model groups. The model group was established by intratracheal injection of bleomycin to induce PF. Flow cytometry was used to detect DC surface markers, and western blot was employed to assess the expression of autophagy-related protein LC3. Lung DCs and peripheral blood CD14+ monocytes were sorted using magnetic beads and differentiated into M0-DCs, which were then subjected to HMGB1 stimulation experiments to assess activation and cytokine secretion. HMGB1-stimulated or untreated M0-DCs were co-cultured with CFSE-labeled naive CD4+ T cells to evaluate T cell proliferation and differentiation. The effects of HMGB1 on DCs activation, cytokine secretion, and autophagy-related protein expression were assessed after treatment with autophagy regulators.</div></div><div><h3>Results</h3><div>The model group showed significantly elevated levels of HMGB1 in serum and lung tissues, accompanied by upregulated activation markers of DCs and increased expression of autophagy-related protein LC3. HMGB1 stimulation significantly enhanced the activation of M0-DCs and the secretion of pro-inflammatory cytokines, promoting the proliferation of CD4+ T cells and their differentiation into Th1 and Th17 subsets. Rapamycin, which enhances autophagy, potentiated HMGB1-mediated DC activation, while 3-MA, which inhibits autophagy, suppressed the effects of HMGB1, further influencing CD4+ T cell differentiation.</div></div><div><h3>Conclusion</h3><div>HMGB1 modulates DC autophagy, thereby affecting their activation and immune responses of CD4+ T cells in bleomycin-induced PF. Targeting HMGB1 and the autophagy pathway may provide new strategies for the treatment of PF.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152906"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in CD8+CD45RA+CCR7− T cells as a potential biomarker for primary Sjögren's syndrome","authors":"Jie Pan ,&nbsp;Rongqiang Wu ,&nbsp;Liuyang He ,&nbsp;Yu Bai ,&nbsp;Jun Ding ,&nbsp;Yan Wang ,&nbsp;Shu Fan ,&nbsp;Zhengyu Zhang ,&nbsp;Ping Zhang ,&nbsp;Chunjian Qi","doi":"10.1016/j.imbio.2025.152914","DOIUrl":"10.1016/j.imbio.2025.152914","url":null,"abstract":"<div><div>In this study, we found that the CD8⁺CD45RA⁺CCR7⁻ T cell subpopulation was increased in the peripheral blood of patients with primary Sjögren's syndrome (pSS) compared with healthy donors. Moreover, both CD8⁺TIM-3⁺ T cells and CD8⁺CD45RA⁺CCR7⁻ T cells were positively correlated with serum anti-SSA antibody concentrations in patients. In animal experiments, prolonged administration of β-glucan (whole glucan particle [WGP]) effectively reduced the onset and progression of pSS. Compared with the control group, the WGP-treated group showed a significant reduction in the proportions of CD4⁺PD-1⁺ T cells, CD4⁺TIM-3⁺ T cells, CD8⁺PD-1⁺ T cells, CD8⁺TIM-3⁺ T cells, and CD8⁺CD45RA⁺CCR7⁻ T cells in the spleens and peripheral blood of non-obese diabetic mice. Notably, β-glucan exhibited therapeutic efficacy comparable to that of hydroxychloroquine sulfate, a conventional treatment for pSS. These findings suggest that the CD8⁺CD45RA⁺CCR7⁻ T cell subpopulation may represent a promising new therapeutic target for the disease.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152914"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QRICH1, as a key effector of endoplasmic reticulum stress, enhances HBV in promoting HMGB1 translocation and secretion in hepatocytes","authors":"Ying Feng ,&nbsp;Yucai Geng ,&nbsp;Zhixiang Liu ,&nbsp;Lin Lu,&nbsp;Chen Cai,&nbsp;Chenke Ding,&nbsp;Shuyu Dong,&nbsp;Bo Gao","doi":"10.1016/j.imbio.2025.152913","DOIUrl":"10.1016/j.imbio.2025.152913","url":null,"abstract":"<div><h3>Background</h3><div>Extracellular high mobility group box 1 (HMGB1) serves as a damage-associated molecular pattern (DAMP) and leads to diverse biological effects, including the aggravation of HBV-related liver diseases. However, mechanisms underlying HMGB1 secretion in HBV-induced hepatic injury and fibrosis remain unclear. Glutamine-rich 1 (QRICH1) is known as a critical effector of endoplasmic reticulum (ER) stress and is elevated in liver diseases. Whether QRICH1 participates in HBV-induced hepatic fibrosis warrants further investigation. Here, we explore the mechanism of HMGB1 secretion during HBV-induced hepatic fibrosis and the effect of QRICH1 on the process.</div></div><div><h3>Methods</h3><div><em>In vivo</em> experiments were conducted using a chronic recombinant cccDNA (rcccDNA) mouse model. Clinical specimens were obtained from Zhongshan Hospital, Fudan University. The levels of QRICH1 and HMGB1 were determined via immunohistochemistry. Liver collagen deposition was determined by Sirius red and Masson's trichrome staining. The serum levels of HMGB1 and indicators of liver injury were detected via ELISA. HMGB1 cyto-translocation was analyzed by Western blotting and quantitative real-time PCR (qRT-PCR).</div></div><div><h3>Results</h3><div>Our findings demonstrated that ER stress promoted HBV-induced hepatic fibrosis in a mouse model. QRICH1 expression and HMGB1 secretion were elevated and positively correlated in rcccDNA mice with ER stress activation and chronic hepatitis B (CHB) patients with severe fibrosis. HBV modulated Sirtuin6 (SIRT6) expression, affecting HMGB1 cyto-translocation via acetylation regulation. Furthermore, QRICH1 enhanced HBV-induced HMGB1 translocation and secretion by regulating HMGB1 transcription.</div></div><div><h3>Conclusion</h3><div>HBV promotes HMGB1 acetylation and cyto-translocation by modulating SIRT6 expression. QRICH1 enhances HBV-induced HMGB1 translocation and secretion by regulating HMGB1 transcription.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152913"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel diagnostic biomarkers regulating macrophages autophagy in ischemic cardiomyopathy: An analysis integrating bulk RNA sequencing with single-cell RNA sequencing","authors":"Weiluan Cen ,&nbsp;Yajin Pan ,&nbsp;Yaohan Tang ,&nbsp;Jianing Yu ,&nbsp;Yixuan Xuan ,&nbsp;Jingyu Huang ,&nbsp;Shanshan Wei ,&nbsp;Jianfeng Zhang","doi":"10.1016/j.imbio.2025.152907","DOIUrl":"10.1016/j.imbio.2025.152907","url":null,"abstract":"<div><div>Macrophage autophagy plays a pivotal role in ischemia cardiomyopathy (ICM). However, the underlying mechanisms and macrophage autophagy-related biomarkers in ICM have not been elucidated. Therefore, this study was designed to explore novel macrophage autophagy-related biomarkers for ICM. The autophagy-related genes were downloaded from the Human Autophagy Modulator and intersected with the differentially expressed genes (DEGs) of GSE46224 identified with “limma” package in R to obtain the autophagy-related DEGs. Immune infiltration analysis showed that macrophages were the dominant immune cells in ICM tissue. Then the macrophage autophagy-related DEGs were identified using the weighted gene co-expression network analysis (WGCNA). A total of six hub genes were obtained from the PPI network. All of the hub genes showed specific diagnostic significance with AUCs higher than 0.7, as also validated in the external dataset GSE116250. RT-qPCR was conducted to detect the mRNA expression levels of hub genes in vivo ICM rat model. Single-cell RNA sequencing analysis was also performed to investigate gene expression profiles. Our study explored the macrophage autophagy-related biomarkers and their relative pathways in ICM, provided novel diagnostic biomarkers for ICM, and gave new insight into the progression mechanism of ICM.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152907"},"PeriodicalIF":2.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinical significance of Peripheral Blood-related Inflammatory Markers in patients with AECOPD","authors":"Dehu Li ,&nbsp;Lanlan Liu ,&nbsp;Jiaxi Lv ,&nbsp;Xianzhi Xiong","doi":"10.1016/j.imbio.2025.152903","DOIUrl":"10.1016/j.imbio.2025.152903","url":null,"abstract":"<div><h3>Objective</h3><div>Peripheral blood-related inflammatory markers, including systemic immune inflammation index (SII), inflammatory response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), have received increasing clinical attention over the years. This study aims to investigate the clinical significance of peripheral blood-related inflammatory markers in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We hope that this study will provide guidance for clinical individualized treatment and management of AECOPD patients.</div></div><div><h3>Methods</h3><div>A total of 254 patients with AECOPD admitted between January 2021 and December 2022 were enrolled in this study and categorized into mild and moderate-to-severe groups. Univariate analysis, Spearman correlation analysis, and receiver operating characteristic curve (ROC) were performed to study the clinical value of peripheral blood-related inflammatory markers. Then, the relationship between the peripheral blood-related inflammatory markers and the risk of readmission owing to acute exacerbation during the first year after discharge was further studied through survival analysis and multivariate Cox regression.</div></div><div><h3>Results</h3><div>The levels of peripheral blood-related inflammatory markers in patients with moderate-to-severe AECOPD were significantly higher than patients in the mild group, and the levels of peripheral blood-related inflammatory markers are positively correlated with the severity of disease. The highest diagnostic accuracy for moderate-to-severe AECOPD was achieved by combining five indexes, with a cut-off value of 0.38 and an AUC of 0.837 (95 % CI: 0.789–0.885). Higher levels of peripheral blood-related inflammatory markers may indicate a higher risk of readmission within one year of hospital discharge in patients with AECOPD, and SII (HR = 3.478, <em>P</em> &lt; 0.001) was an independent risk factor. Besides, higher levels of peripheral blood-related inflammatory markers also suggest impaired pulmonary ventilation function and enlarged right ventricular diameter.</div></div><div><h3>Conclusions</h3><div>Peripheral blood-related inflammatory markers (SII, SIRI, NLR, PLR, MLR) can serve as a reference for identifying patients with moderate-to-severe AECOPD. Patients with higher levels of peripheral blood-related inflammatory markers are more susceptible to experiencing acute exacerbation and readmission events within one year after hospital discharge. Peripheral blood-related inflammatory markers can assist clinicians in evaluating the condition and predicting the risk of readmission in patients with AECOPD more scientifically and objectively.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152903"},"PeriodicalIF":2.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker identification for rheumatoid arthritis with inadequate response to DMARD and TNF therapies using multidimensional analyses","authors":"Leyuan Li ,&nbsp;Hui Guo ,&nbsp;Weijin Zhang ,&nbsp;Xi Xiang ,&nbsp;Jun Chi ,&nbsp;Mengmeng Zhang ,&nbsp;Jiali Chen ,&nbsp;Zhimin Wang ,&nbsp;Liping Dai","doi":"10.1016/j.imbio.2025.152901","DOIUrl":"10.1016/j.imbio.2025.152901","url":null,"abstract":"<div><h3>Purpose</h3><div>Rheumatoid arthritis (RA) is an immune system disorder disease accompanied with severe joint damage. However, the molecular mechanism of RA with insensitive to medicine remains insufficient. Thus, this study aims to identify the biomarkers of RA patients with inadequate responses (IR) toward disease-modifying antirheumatic drug (DMARD) and antitumor necrosis factor (TNF) therapies, using multidimensional analyses.</div></div><div><h3>Methods</h3><div>Gene expression data GSE45291 originating from clinics were downloaded from the Gene Expression Omnibus public database (GEO). Differentially expressed genes (DEGs) closely associated with DMARD&amp;TNF-IR RA were identified using the Limma R package. Weighted gene co-expression network analysis (WGCNA) was carried out to identify critical genes. The CIBERSORT algorithm and single sample Gene Set Enrichment Analysis (ssGSEA) were employed for immune infiltration analysis and functional enrichment analysis, respectively. Lastly, mRNA expression levels of the identified hub genes in inflammatory conditions of collagen-induced arthritis (CIA) rats and lipopolysaccharide (LPS)-induced RAW264.7 cells were further observed using RT-qPCR.</div></div><div><h3>Results</h3><div>In this work, a total of 17 genes were identified as hub genes. Of these, the expression levels of UHMK1, ELK4, APOC2, and SFT2D1 were significantly lowered in inflammatory conditions. GSEA indicated B cells with the immune-related genes play an essential role in the course of DMARD&amp;TNF-IR RA. Notable differences in immune cell proportions (activated. Dendritic. cell, CD56 bright. Natural. killer. Cell, gamma. Delta. T. cell, MDSC, macrophage) were observed between normal and disease groups, suggesting immune involvement.</div></div><div><h3>Conclusion</h3><div>The findings of this study provide additional understanding of the detection of DMARD&amp;TNF-IR RA.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152901"},"PeriodicalIF":2.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}