Inflammation Research最新文献

{"title":"The impact for causal associations between common diseases and inflammatory bowel disease: a disease-wide bidirectional Mendelian randomization study.","authors":"Yuxuan Sun, Zixin Liang, Zehua Ou, Lei Gao, Yong-Fei Wang, Jinqiu Yuan, Guangjun Yu, Rui Sun","doi":"10.1007/s00011-026-02304-8","DOIUrl":"10.1007/s00011-026-02304-8","url":null,"abstract":"<p><strong>Objectives: </strong>Observational studies on associations between various diseases and inflammatory bowel disease (IBD) are often limited by confounding and reverse causation. We aimed to assess potential causal relationships between a wide range of diseases and IBD, including Crohn's disease (CD) and ulcerative colitis (UC).</p><p><strong>Methods: </strong>We performed a comprehensive bidirectional Mendelian randomization (MR) analysis of 104 common diseases and IBD traits using the generalized summary-data-based MR (GSMR) approach. Genome-wide association study (GWAS) summary statistics for diseases were obtained from the MRC Integrative Epidemiology Unit, and IBD data from the International IBD Genetics Consortium. Summary-data-based MR (SMR) integrating GWAS and expression quantitative trait locus data was applied to identify pleiotropic genes associated with IBD.</p><p><strong>Results: </strong>MR analyses identified 38, 34, and 52 exposures significantly associated with IBD, UC, and CD, respectively. Childhood- and adult-onset asthma showed distinct causal effects on UC and CD. Reverse MR indicated associations between IBD traits and 15 diseases, including multiple sclerosis. SMR identified RGS14 and CARD9 as pleiotropic genes linked to IBD, suggesting shared genetic mechanisms with asthma and multiple sclerosis.</p><p><strong>Conclusions: </strong>These findings provide evidence for causal links and shared immune-related genetic mechanisms underlying IBD, highlighting potential targets for future research.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMJ-associated transcriptomic remodeling correlates with disease severity in juvenile dermatomyositis.","authors":"Cristina Sanfilippo, Paola Castrogiovanni, Rosa Imbesi, Paolo Fagone, Grazia Scuderi, Giuseppe Grosso, Giuseppe Musumeci, Daniele Tibullo, Michele Vecchio, Michelino Di Rosa","doi":"10.1007/s00011-026-02338-y","DOIUrl":"10.1007/s00011-026-02338-y","url":null,"abstract":"<p><strong>Background: </strong>Juvenile dermatomyositis (JDM) is a rare systemic autoimmune disease primarily affecting children, with a female predominance. While muscle fiber inflammation has been extensively investigated, the contribution of the neuromuscular junction (NMJ) and its cellular microenvironment to JDM pathogenesis remains poorly understood. This study aimed to characterize NMJ-related gene expression patterns in JDM to identify potential pathogenic mechanisms and candidate biomarkers.</p><p><strong>Methods: </strong>An integrated transcriptomic analysis was conducted using two publicly available microarray datasets comprising 40 JDM patients and 22 healthy controls. Twenty-one genes representing five major NMJ functional categories were analyzed: cholinergic transmission, nicotinic acetylcholine receptors, extracellular matrix components, glial markers, and postsynaptic signaling molecules. Differential expression, discriminatory performance, correlation, clustering, and tissue deconvolution analyses were performed.</p><p><strong>Results: </strong>Eighteen of the 21 NMJ-related genes were significantly differentially expressed in JDM (FDR-adjusted p < 0.05). Among these, MBP showed the most pronounced dysregulation and high discriminatory performance (AUC = 0.976, p = 6.10 × 10^-16), with marked downregulation associated with increased muscle weakness. Other genes also demonstrated strong discriminatory performance, including AGRN (AUC = 0.941), NID1 (AUC = 0.932), CHRNA1 (AUC = 0.927), NRXN3 (AUC = 0.916), and RYR1 (AUC = 0.913). Correlation analyses revealed disruption of physiological co-expression patterns and the emergence of disease-specific interactions, including altered associations between glial markers and cholinergic components. CHRNA1 expression correlated with both muscle and skin disease activity scores, whereas GFAP expression was associated with disease duration. Clustering analysis indicated a reorganization of NMJ-related gene networks in JDM. Tissue deconvolution suggested that CHRNA1 expression may reflect a shift from inflammatory cell infiltration toward preservation of muscle cell identity.</p><p><strong>Conclusions: </strong>These findings reveal widespread NMJ-associated transcriptomic remodeling in JDM, involving synaptic, cholinergic, and neuroglial components. The identification of candidate transcriptional biomarkers, particularly MBP and CHRNA1, which show association with disease activity, may warrant further evaluation as potential monitoring tools in independent cohorts. Overall, this study supports a role for NMJ-associated transcriptomic remodeling in JDM pathophysiology and suggests new avenues for mechanistic investigation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897172","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":"Synthetic viral RNA mimetics induce neuronal loss through microglial phagocytosis.","authors":"Katryna Pampuscenko, Silvija Jankeviciute, Danielius Umbrasas, Vilmante Borutaite","doi":"10.1007/s00011-026-02357-9","DOIUrl":"10.1007/s00011-026-02357-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Microglial Toll-like receptor (TLR) 3 and 7 signalling is induced during active viral inflammation and emerging evidence suggests that it may persist in post-infectious state due to continued presence of free viral RNA. In addition, TLR3 and TLR7 can recognize self-derived RNA, leading to sustained microglial activation. TLR3 and TLR7 activation have also been implicated in neurodegenerative processes in major neurodegenerative disorders. However, the link between chronic TLR3- and TLR7-mediated neuroinflammation and progressive neuronal damage remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Neuronal-glial co-cultures and pure microglial cell cultures isolated from Wistar rat brain tissue were treated with synthetic TLR3 and TLR7 receptor activators-poly(I:C) and loxoribine. Neuronal density and viability were evaluated by double nuclear staining with Hoechst 33342 and propidium iodide. Microglial cell number and area were assessed by isolectin-IB&lt;sub&gt;4&lt;/sub&gt; labelling. Phosphatidylserine exposure on neuronal membranes was detected by Annexin V-Cy3 labelling. Evaluation of microglia activation (Iba-1 and CD68 expression), caspase-3 activation, synaptic density (synapsin-1/PSD-95 colocalization), neuronal (NeuN-positive cells) detection inside microglia were carried out by immunostaining. Levels of TNF-α, lactadherin and galectin-3 in cell culture medium were quantified by ELISA, while nitric oxide production was determined using Griess assay. Microglial phagocytic activity was assessed by measuring the uptake of phosphatidylserine-coated microparticles.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In this study, we show that poly(I:C) and loxoribine induced loss of viable neurons without any increase in apoptosis (chromatin condensation/caspase-3 negative) or necrosis (propidium iodide negative) in neuronal-glial co-cultures. Neuronal loss was associated with alterations in microglial number and morphology, as well as enhanced production of pro-inflammatory factors and upregulated Iba-1 and CD68 expression. In co-cultures, poly(I:C) and loxoribine induced phosphatidylserine exposure on neuronal plasma membranes acting as 'eat-me' signal and opsonin lactadherin and galectin-3 production promoting phosphatidylserine recognition. NeuN-positive neurons exhibiting normal chromatin distribution were found inside of microglial cells, indicating their removal through phagocytic uptake. Under exposure to poly(I:C) and loxoribine, microglial cells showed enhanced phagocytic activity, evidenced by increased uptake of phosphatidylserine-covered polystyrene beads. Moreover, poly(I:C) and loxoribine were shown to induce microglia-dependent synaptic loss, indicating that TLR3 and TLR7 associated neuroinflammation contributes to both synaptic and neuronal pathology.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Overall, our data suggest that synthetic TLR3 and TLR7 ligands poly(I:C) and loxoribine cause microglia-mediated neuronal and synaptic loss in n","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897263","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":"TET2 aggravates podocyte mitotic catastrophe and renal injury in diabetic nephropathy via m5C-dependent downregulation of Wee1 and activation of CDK1-cyclinB1 signaling.","authors":"Jie Feng, Hongjuan Dong, Yi Yang, Liyi Xie, Wanhong Lu, Yurui Guo, Ranran Kong","doi":"10.1007/s00011-026-02346-y","DOIUrl":"10.1007/s00011-026-02346-y","url":null,"abstract":"<p><p>Podocyte injury and loss in diabetic nephropathy (DN) are driven by mitotic catastrophe (MC), a disastrous cell death caused by aberrant cell cycle re-entry. Ten-eleven translocation 2 (TET2), a 5-methylcytosine (m5C) RNA demethylase, was upregulated in DN and regulated cell proliferation. Here, we explored whether TET2 mediates podocyte MC in DN using Adriamycin (ADM) and high glucose (HG) in vitro, and both STZ-induced and db/db diabetic mouse models in vivo. TET2 was upregulated in human diseased kidneys and injured podocytes, and its expression correlated with disease severity and podocyte loss. EdU staining and flow cytometry verified that ADM/HG facilitated cell proliferation and G2/M phase transition via elevated CDK1-cyclin B1 phosphorylation; meanwhile, ADM/HG increased reactive oxygen species and malondialdehyde levels. TET2 overexpression further enhanced ADM/HG-induced podocyte MC and oxidative stress, whereas TET2 knockdown had the opposite effect. Mechanistically, TET2 reduced Wee1 mRNA stability in an m5C-dependent manner, leading to CDK1-cyclin B1 activation. Rescue experiments confirmed that Wee1 reintroduction rescued TET2-driven MC and oxidative stress, while Wee1 silencing abolished the protection from TET2 knockdown. In vivo, TET2 depletion or Wee1 overexpression alleviated podocyte MC, renal injury, and apoptotic podocytes in both diabetic models. Collectively, TET2 promotes podocyte MC and aggravates DN via TET2-mediated m5C demethylation that suppresses Wee1 expression and activates CDK1-cyclin B1, suggesting that this axis may represent a candidate pathway in the context of DN.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897298","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 DLL4 in Neutrophil Aging and Impaired Clearance in Sepsis.","authors":"Hui Jin, Saoirse Holland, Alok Jha, Monowar Aziz, Ping Wang","doi":"10.1007/s00011-026-02315-5","DOIUrl":"10.1007/s00011-026-02315-5","url":null,"abstract":"<p><p>Sepsis remains a major cause of mortality, largely due to acute lung injury (ALI) driven by excessive neutrophil mediated inflammation. We recently identified a pathogenic subset of DLL4⁺ neutrophils that expands in inflamed lungs and promotes ALI, yet the underlying mechanisms remain unclear. Here, we investigated how DLL4⁺ neutrophils modulate alveolar macrophage (AM) function to exacerbate lung injury. AMs were treated with DLL4⁺ neutrophils or recombinant DLL4 (rmDLL4), and macrophage polarization was assessed by flow cytometry. Conditioned medium was subsequently applied to bone marrow-derived neutrophils (BMDNs) to evaluate neutrophil aging and CD47 expression (don't eat me signal on neutrophils). We showed that DLL4⁺ neutrophils activate the Notch1 signaling pathway in AMs, promoting toward a proinflammatory M1 phenotype. M1 cells markedly upregulate leukotriene B4 (LTB4) production through 5-lipoxygenase activation (5-LOX), inducing the accumulation of aged neutrophils (CXCR4^hiCD62L^low). These aged neutrophils markedly increase CD47 expression, leading to impaired macrophage mediated phagocytosis and amplified lung inflammation. Importantly, we developed a novel DLL4-Notch1 inhibitory peptide (NDI) that reprograms AMs toward an anti-inflammatory M2 phenotype, reduces LTB4 release and aged neutrophils, lowers CD47 expression in a murine model of sepsis. Together, we identify DLL4⁺ neutrophils as key orchestrators of macrophage dysregulation in sepsis-induced ALI and demonstrate NDI may represent a potential therapeutic candidate in sepsis-induced ALI.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887415","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":"Immunometabolic regulation and tissue-resident immunity in autoimmune uveitis: from genetic susceptibility to the gut-spleen-eye axis.","authors":"Liping Lin, Jingqi Zhang, Xuejun Xie","doi":"10.1007/s00011-026-02350-2","DOIUrl":"10.1007/s00011-026-02350-2","url":null,"abstract":"<p><strong>Objective and design: </strong>This narrative review synthesizes current evidence on the immunopathogenesis of autoimmune uveitis(AU), with particular emphasis on genetic susceptibility, immunometabolic dysregulation, tissue-resident immunity, and the proposed gut-spleen-eye immunometabolic axis.</p><p><strong>Material and subjects: </strong>Published genetic, clinical, experimental, and in vitro studies addressing immune-mediated uveitis and related mechanistic pathways were summarized.</p><p><strong>Treatment: </strong>Not applicable.</p><p><strong>Methods: </strong>We summarized evidence on subtype-associated genetic factors, Th17-centered immunometabolic reprogramming, retinal microglial and myeloid responses, innate-adaptive immune interactions, and gut-derived metabolic regulation, with attention to evidence level and translational relevance.</p><p><strong>Results: </strong>Genetic susceptibility showed the clearest subtype specificity, including HLA-B27/ERAP1-associated acute anterior uveitis, IL23R-C1orf141-associated Vogt-Koyanagi-Harada disease, HLA-B51-ERAP1-associated Behçet disease, and NOD2-associated Blau syndrome. Experimental and clinical evidence further links Th17 dysregulation to AU, whereas most pathway-specific metabolic, microglial, macrophage, retinal vascular, and gut-derived mechanisms remain supported mainly by experimental autoimmune uveitis or in vitro studies. The proposed HDCA-red pulp macrophage-oleic acid pathway may integrate systemic metabolic and immune regulation, but its relevance to defined human AU subtypes remains uncertain.</p><p><strong>Conclusions: </strong>AU is mechanistically heterogeneous, and current evidence supports phenotype-stratified validation of candidate pathways before translation into targeted therapeutic strategies.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792550","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":"Toxoplasma gondii infection reduces CD59 expression through downregulation of JAK2/STAT3 signaling axis to enhance decidual NK cell cytotoxicity via the RAS/MAPK pathway.","authors":"Shuyan Wang, Luyun Huo, Yan Zou, Ruohan Yang, Xiao Wang, Haixia Zhang, Liqin Ren, Jing Yang, Jie Li, Xuemei Hu, Yushan Ren","doi":"10.1007/s00011-026-02344-0","DOIUrl":"10.1007/s00011-026-02344-0","url":null,"abstract":"<p><strong>Objective and design: </strong>Toxoplasma gondii (T. gondii) infection disrupts pregnancy by modulating decidual natural killer (dNK) cells function. This study investigates how T. gondii regulates CD59 expression in dNK cells and its impact on pregnancy outcomes.</p><p><strong>Material or subjects: </strong>T. gondii-infected wild-type (WT) C57BL/6 and cd59a^-/- pregnant mice, as well as human primary dNK cells, were used.</p><p><strong>Treatment: </strong>The pregnant mice were challenged intraperitoneally with T. gondii tachyzoites. Decidual immune cells and dNK cells were also infected with T. gondii in vitro.</p><p><strong>Methods: </strong>Adverse outcomes were observed after T. gondii infection. Protein expression and transcriptional activity were evaluated using flow cytometry, Western blot, chromatin immunoprecipitation (ChIP)-PCR and dual-luciferase reporter assays. dNK cytotoxicity was measured by lactate dehydrogenase (LDH) release.</p><p><strong>Results: </strong>T. gondii downregulated CD59 expression both in vivo and in vitro. In dNK cells, T. gondii suppressed the JAK2/STAT3 pathway, reducing p-STAT3 binding to the cd59 promoter. CD59 downregulation subsequently activated the Ras/MAPK pathway, leading to elevated IFN-γ and perforin production and enhanced cytotoxicity. Lack of cd59a exacerbated adverse pregnancy outcomes caused by T. gondii infection.</p><p><strong>Conclusions: </strong>T. gondii suppresses CD59 in dNK cells via JAK2/STAT3 inhibition, which enhances dNK cell cytotoxicity through Ras/MAPK activation, contributing to poor pregnancy outcomes.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792546","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":"LncRNA SNHG14 drives alveolar inflammation in bronchopulmonary dysplasia via DNMT3a-mediated epigenetic silencing of miR-214-3p.","authors":"Hui Hong, Xiaoxia Li, Jing Li, Yuhang Liu, Zhiqun Zhang","doi":"10.1007/s00011-026-02345-z","DOIUrl":"10.1007/s00011-026-02345-z","url":null,"abstract":"<p><strong>Objective and design: </strong>This experimental study investigated whether lncRNA SNHG14 contributes to hyperoxia-associated bronchopulmonary dysplasia (BPD) through DNMT3a-mediated epigenetic regulation of miR-214-3p and evaluated TfR-modified exosome-mimetic nanovesicles as an siRNA delivery platform.</p><p><strong>Material or subjects: </strong>Hyperoxia-exposed murine alveolar epithelial type II cells and neonatal C57BL/6J mice were used.</p><p><strong>Treatment: </strong>Cells and neonatal mice were exposed to 85% O2 or normoxia. In vivo groups included normoxia, BPD, BPD + blank EMNVs, BPD + free siSNHG14, BPD + TfR-EMNVs-siSNHG14, and BPD + TfR-EMNVs-siSNHG14 + miR-214-3p antagomir.</p><p><strong>Methods: </strong>Transcriptomic, miRNA, methylation, pull-down, RIP, ChIP-qPCR, luciferase, biodistribution, histological, biochemical, and exploratory innate immune assays were performed.</p><p><strong>Results: </strong>SNHG14 was upregulated after hyperoxia. SNHG14 silencing reduced epithelial injury, apoptosis, inflammation, and EMT-related changes, and was associated with decreased DNMT3a enrichment and methylation at the examined miR-214-3p promoter region. TfR-EMNVs-siSNHG14 improved siRNA delivery and lung-preferential fluorescence accumulation without overt short-term liver, kidney, or interferon-response toxicity.</p><p><strong>Conclusions: </strong>The SNHG14/DNMT3a/miR-214-3p axis may contribute to experimental BPD-like alveolar injury, and TfR-EMNVs-siSNHG14 warrants further pharmacokinetic, safety, and clinical-sample validation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792573","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":"Distinct miRNA expression patterns in circulating eosinophil subtypes and their subtype-derived exosomes in allergic asthma.","authors":"Egle Vasyle, Andrius Januskevicius, Airidas Rimkunas, Jolita Palacionyte, Skaidrius Miliauskas, Kestutis Malakauskas","doi":"10.1007/s00011-026-02348-w","DOIUrl":"https://doi.org/10.1007/s00011-026-02348-w","url":null,"abstract":"<p><strong>Background: </strong>Lung-resident (rEos) and inflammatory (iEos) eosinophil subtypes were initially characterized in mouse models of asthma and have been proposed to contribute differentially to inflammation and remodeling in human allergic asthma (AA). While microRNAs (miRNAs) and their transfer through exosomes may play important regulatory roles in immune signaling in asthma, miRNA profiles specific to eosinophil subtypes remain uncharacterized. This study aimed to identify distinct miRNA expression patterns in circulating eosinophil subtypes and subtype-derived exosomes from AA patients.</p><p><strong>Methods: </strong>Peripheral blood iEos and rEos were isolated from 22 AA patients and 21 healthy subjects (HS). Next-generation sequencing (NGS) was used to identify differentially expressed miRNAs, and 16 candidates were subsequently selected for validation by quantitative polymerase chain reaction (qPCR) in eosinophil subtypes and in subtype-derived exosomes.</p><p><strong>Results: </strong>NGS revealed 62 differentially expressed miRNAs in AA iEos and 35 in AA rEos compared with corresponding HS eosinophil subtypes. qPCR confirmed differential expression for 14 of 16 selected miRNAs in eosinophils or their exosomes between AA and HS. miRNA expressions distinguished AA from HS; furthermore, iEos and rEos showed distinct miRNA patterns within the AA group. Notably, AA rEos-derived exosomes showed greater miRNA enrichment than iEos-derived exosomes, implying active exosomal communication. Finally, validated miRNA patterns suggest a predominance of regulatory functions in rEos, whereas iEos displayed a profile consistent with pro-inflammatory activation.</p><p><strong>Conclusions: </strong>This study provides molecular evidence that eosinophil subtypes are functionally specialized in AA. The differential miRNA patterns of rEos and iEos highlight their complementary regulatory and pro-inflammatory roles and suggest that eosinophil-derived miRNAs merit further investigation as potential biomarkers or modulators of airway inflammation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPR132 antagonists alleviate atherosclerosis by suppressing M1 polarization and subsequent VSMCs proliferation and migration as revealed by transcriptomic profiling.","authors":"Yin Feng, Zheng Cao, Fan Zhang, Xinwei Zhou, Lilliane Aol, Li Su, Liqun He","doi":"10.1007/s00011-026-02342-2","DOIUrl":"https://doi.org/10.1007/s00011-026-02342-2","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis (AS) is a chronic inflammatory disorder with substantial global prevalence, wherein macrophage polarization and vascular smooth muscle cells (VSMCs) phenotypic switching are critical pathogenic events. Although G protein-coupled receptor 132 (GPR132) is markedly expressed in macrophages, its specific role and mechanism in AS-associated macrophage polarization remain incompletely understood.</p><p><strong>Methods: </strong>Pharmacological antagonism of GPR132 was evaluated in high-fat diet-fed ApoE^-/- mice. Integrated single-cell RNA sequencing and transcriptome analyses from GEO datasets were performed to profile GPR132 expression in murine and human atherosclerotic plaques. In vitro, GPR132 overexpression and knockout macrophages were generated to assess M1/M2 polarization markers, and an indirect co‑culture system with VSMCs was established. Mechanistic investigations employed RNA‑sequencing and Western blotting, with pathway inhibition using SB203580 or GPR132 antagonists.</p><p><strong>Results: </strong>GPR132 antagonism attenuated atherosclerotic lesion progression and reduced pro‑inflammatory cytokine secretion without altering lipid profiles. GPR132 was enriched in pro‑inflammatory (M1‑like) macrophage subpopulations within plaques, which also upregulated VSMC‑promoting growth factors. GPR132 overexpression promoted M1 macrophage polarization and suppressed IL‑4‑induced M2 macrophage polarization, whereas knockout enhanced M2 and attenuated M1. Conditioned medium from GPR132‑overexpressing macrophages significantly enhanced VSMCs proliferation and migration. Mechanistically, GPR132 drove M1 macrophage polarization primarily through activation of the p38/MAPK signaling pathway, an effect reversible by SB203580 or GPR132 antagonists.</p><p><strong>Conclusions: </strong>GPR132 promotes pro‑inflammatory macrophage polarization via p38/MAPK signaling, and its antagonism mitigates atherosclerotic progression by suppressing inflammatory microenvironments and VSMCs proliferation/migration, highlighting GPR132 as a potential therapeutic target for AS.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}