Immunobiology最新文献

{"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":"Exploring the role of diosgenin in modulating RUNX1 and HIPK2 transcription to mitigate Primary Sjögren's Syndrome","authors":"Yiwei Pan ,&nbsp;Lunquan Wei ,&nbsp;Han Liu ,&nbsp;Fang Wang ,&nbsp;Minhua Wang ,&nbsp;Meijia Li ,&nbsp;Pengfei Cheng ,&nbsp;Xing Yan","doi":"10.1016/j.imbio.2025.152910","DOIUrl":"10.1016/j.imbio.2025.152910","url":null,"abstract":"<div><h3>Background</h3><div>Primary Sjögren's Syndrome (pSS) is a chronic autoimmune disease characterized by inflammation of the exocrine glands, resulting in symptoms like dry mouth and eyes. Despite existing symptomatic treatments, underlying immune dysregulation remains undefined. Diosgenin, a steroidal saponin derived from Mai Dong, shows potential in modulating immune responses, but its mechanism in pSS remains underexplored.</div></div><div><h3>Methods</h3><div>This study investigated the immunomodulatory effects of diosgenin on pSS using in vivo and in vitro approaches. In vivo, salivary flow rate measurement, histological analysis, quantitative real-time PCR (qRT-PCR), flow cytometry and Western blot were performed on NOD/ShiLtJ mice after treatment with diosgenin at various concentrations. In vitro, CD4⁺ T cells isolated from these mice were treated with diosgenin to assess T cell differentiation via flow cytometry, qRT-PCR, Enzyme-Linked Immunosorbent Assay (ELISA) and Western blot, where Homeodomain-Interacting Protein Kinase 2 (HIPK2) overexpression and Runt-associated transcription factor 1 (RUNX1) knockdown were manipulated.</div></div><div><h3>Results</h3><div>Diosgenin stabilized salivary flow rates, reduced lymphocytic infiltration and inflammatory cytokines levels, upregulated RUNX1 and downregulated HIPK2, which modified T cell dynamics by promoting regulatory T cells (Treg) and reducing T helper 17 (Th17) populations. However, HIPK2 overexpression reversed the effects of diosgenin on inhibiting Th17 differentiation and inflammatory cytokines levels and promoting RUNX1 level. Additionally, RUNX1 knockdown also offset the suppressive effects of diosgenin on Th17 differentiation, inflammatory cytokine levels, and HIPK2 expression.</div></div><div><h3>Conclusion</h3><div>Diosgenin effectively impacts immune responses in pSS, potentially through the modulation of RUNX1 and HIPK2 transcription factors, leading to a reduction in Th17-mediated inflammation.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152910"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137282","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":"A Tertiary lymphoid structures-based pathological score predicts survival and recurrence in colorectal Cancer patients","authors":"Marion Le Rochais ,&nbsp;Marie Morvan ,&nbsp;Servane Bouzeloc ,&nbsp;Jean-Baptiste Nousbaum ,&nbsp;Matthieu Guillard ,&nbsp;Pierre Le Noac'h ,&nbsp;Soizic Garaud ,&nbsp;Arnaud Uguen","doi":"10.1016/j.imbio.2025.152911","DOIUrl":"10.1016/j.imbio.2025.152911","url":null,"abstract":"<div><h3>Background &amp; Aim</h3><div>Colorectal cancer (CRC) is a major global health burden. The immune response within the tumor microenvironment (TME), especially the presence of tertiary lymphoid structures (TLS), plays a critical role in prognosis. However, current prognostic tools often overlook this immune component. This study aimed to characterize TLS in CRC and develop a TLS-score correlating with survival outcomes.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of 7895 TLS from 806 CRC patients using data from the Finistere Registry of Digestive Tumors. Hematoxylin-eosin-saffron (HES) staining and immunohistochemistry (IHC) were employed for TLS quantification to explore their relationship with survival and recurrence metrics.</div></div><div><h3>Results</h3><div>Patients with microsatellite instability (MSI) demonstrated higher TLS density and more mature TLS. Both TLS density and maturation showed significant correlations with overall survival (OS) and disease-free survival (DFS). Kaplan-Meier analysis revealed that increased TLS density and GC-like maturation correlated with improved OS and DFS. Our novel pathological TLS score, integrating density and maturation, effectively stratified patients by survival and recurrence risk, distinguishing high-risk individuals (score 0–1–2) with poorer outcomes from low-risk patients (score 3–4) with better prognosis (<em>p</em> &lt; 0.0001), particularly in stage II–III cases.</div></div><div><h3>Conclusion</h3><div>TLS density and maturation are robust prognostic markers in CRC. The proposed TLS score may aid pathologists in identifying patients at higher recurrence risk and poorer survival, guiding clinical decisions for monitoring and potential adjuvant therapies. Further validation of these findings is essential before clinical implementation.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152911"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098891","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":"Systemic lupus erythematosus as the paradigm for understanding the complex immune relationships and therapeutic opportunities for targeting complement in autoimmune diseases","authors":"V. Michael Holers","doi":"10.1016/j.imbio.2025.152915","DOIUrl":"10.1016/j.imbio.2025.152915","url":null,"abstract":"<div><div>Complement therapeutics have been increasingly tested and approved for human diseases, often in orphan diseases with strong and apparently causal genetic linkage or mutation-associated features. However, the complement system has been demonstrated to be activated in essentially all human inflammatory, ischemic and autoimmune diseases, suggesting the possibility of even wider therapeutic applications. The goal of this manuscript is to review some of the evidence supporting a wide role for complement in the specific treatment of autoimmune diseases, especially as recent approvals in autoantibody-driven diseases are opening the door to others of these indications. However, in part because of a dearth of complement biomarker data obtained during clinical trials, it is not known what findings would help to predict therapeutic success in other autoimmune diseases. To frame the discussion, it is relevant to point out that the disease systemic lupus erythematosus (SLE) has been among the most extensively studied autoimmune disease with regards to the varied roles of the complement system, and there are available both human phenotypic studies and murine model data. Because of that history, SLE will be focused upon herein, the many roles of complement in SLE will be reviewed, and informative comparisons to other autoimmune diseases will be made. In aggregate, experimental and phenotypic data suggest that each human autoimmune disease deserves careful attention to the possibility that a specific complement inhibitor targeting the most relevant complement convertase or component will be of benefit, and thus therapeutic approaches should be tested using informative biomarker-driven clinical trial strategies.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152915"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125178","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}

{"title":"Ureaplasma urealyticum GrpE protein elicits glycolysis-mediated inflammatory responses through TLR2 in macrophages","authors":"Jing Xie ,&nbsp;Nan Xie ,&nbsp;Chang Liu ,&nbsp;Zhemin Huang ,&nbsp;Min Du ,&nbsp;Hao Hu ,&nbsp;Kang Zheng ,&nbsp;Jiaofeng Peng ,&nbsp;Ranhui Li","doi":"10.1016/j.imbio.2025.152902","DOIUrl":"10.1016/j.imbio.2025.152902","url":null,"abstract":"<div><div>The pathogenesis of <em>Ureaplasma urealyticum</em> infection is linked to the host inflammatory response; however, the specific molecular mechanisms underlying this phenomenon have not been fully elucidated. GrpE is a chaperonin that accelerates ADP release and ATP binding to DnaK, thereby enhancing the chaperone function of the HSP70 system under stress. However, alternative activities such as pro-inflammatory responses remain poorly understood. In this study, we report that the <em>U. urealyticum</em> GrpE exerts as a cytokine-inducing virulence factor toward macrophages. Using gene-knockout mice and specific inhibitors, we found that GrpE-induced pro-inflammatory cytokine expression was mediated by the TLR2/STAT3 pathway. We also found that glycolysis was essential for this pro-inflammatory response. Mechanistically, GrpE treatment stimulated STAT3-dependent accumulation of citric acid and acetyl-CoA, promoting histone acetylation and potent pro-inflammatory responses. Our results indicate that glycolysis plays a role in the inflammatory response induced by GrpE through the TLR2/STAT3 pathway and contributes to the glycolysis-mediated inflammatory response, offering a fresh understanding of the development of <em>U. urealyticum</em> infection.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152902"},"PeriodicalIF":2.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860148","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}