Autoimmunity最新文献_第3页

Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in Crohn's disease by integrating bioinformatics and machine learning. 通过整合生物信息学和机器学习，分析和验证克罗恩病的诊断生物标志物和免疫细胞浸润特征。

IF 3.3 4区医学

Autoimmunity Pub Date : 2024-12-01 Epub Date: 2024-10-30 DOI: 10.1080/08916934.2024.2422352

Xiao-Jun Ren, Man-Ling Zhang, Zhao-Hong Shi, Pei-Pei Zhu

{"title":"Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in Crohn's disease by integrating bioinformatics and machine learning.","authors":"Xiao-Jun Ren, Man-Ling Zhang, Zhao-Hong Shi, Pei-Pei Zhu","doi":"10.1080/08916934.2024.2422352","DOIUrl":"https://doi.org/10.1080/08916934.2024.2422352","url":null,"abstract":"Crohn's disease (CD) presents significant diagnostic and therapeutic challenges due to its unclear etiology, frequent relapses, and limited treatment options. Traditional monitoring often relies on invasive and costly gastrointestinal procedures. This study aimed to identify specific diagnostic markers for CD using advanced computational approaches. Four gene expression datasets from the Gene Expression Omnibus (GEO) were analyzed, identifying differentially expressed genes (DEGs) through gene set enrichment analysis in R. Key biomarkers were selected using machine learning algorithms, including LASSO logistic regression, SVM‑RFE, and Random Forest, and their accuracy was assessed using receiver operating characteristic (ROC) curves and nomogram models. Immune cell infiltration was analyzed using the CIBERSORT algorithm, which helped reveal associations between diagnostic markers and immune cell patterns in CD. From a training set of 605 CD samples and 82 normal controls, we identified eight significant biomarkers: LCN2, FOLH1, CXCL1, FPR1, S100P, IGFBP5, CHP2, and AQP9. The diagnostic model showed high predictive power (AUC=0.954) and performed well in external validation (AUC = 1). Immune cell infiltration analysis highlighted various immune cells involved in CD, with all diagnostic markers strongly linked to immune cell interactions. Our findings propose candidate hub genes and present a nomogram for CD diagnosis, providing potential diagnostic biomarkers for clinical applications in CD.","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2422352"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543384","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}

引用次数: 0

Identification the role of necroptosis in rheumatoid arthritis by WGCNA network. 通过 WGCNA 网络鉴定坏死在类风湿性关节炎中的作用。

IF 3.5 4区医学

Autoimmunity Pub Date : 2024-12-01 Epub Date: 2024-06-13 DOI: 10.1080/08916934.2024.2358069

Feige Nian, Yiwen Wang, Mingfeng Yang, Bin Zhang

{"title":"Identification the role of necroptosis in rheumatoid arthritis by WGCNA network.","authors":"Feige Nian, Yiwen Wang, Mingfeng Yang, Bin Zhang","doi":"10.1080/08916934.2024.2358069","DOIUrl":"https://doi.org/10.1080/08916934.2024.2358069","url":null,"abstract":"Rheumatoid arthritis (RA) is the predominant manifestation of inflammatory arthritis, distinguished by an increasing burden of morbidity and mortality. The intricate interplay of genes and signalling pathways involved in synovial inflammation in patients with RA remains inadequately comprehended. This study aimed to ascertain the role of necroptosis in RA, as along with their associations with immune cell infiltration. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were employed to identify central genes for RA. In this study, identified total of 28 differentially expressed genes (DEGs) were identified in RA. Utilising WGCNA, two co-expression modules were generated, with one module demonstrating the strongest correlation with RA. Through the integration of differential gene expression analysis, a total of 5 intersecting genes were discovered. These 5 hub genes, namely fused in sarcoma (FUS), transformer 2 beta homolog (TRA2B), eukaryotic translation elongation factor 2 (EEF2), cleavage and polyadenylation specific factor 6 (CPSF6) and signal transducer and activator of transcription 3 (STAT3) were found to possess significant diagnostic value as determined by receiver operating characteristic (ROC) curve analysis. The close association between the concentrations of various immune cells is anticipated to contribute to the diagnosis and treatment of RA. Furthermore, the infiltration of immune cells mentioned earlier is likely to exert a substantial influence on the initiation of this disease.","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2358069"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309930","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}

引用次数: 0

iTreg cells-secreted IL10 alleviates lupus nephritis through inactivating lncRNA HAR1A transcription to suppress SMARCD1-mediated iNOS activation. iTreg细胞分泌的IL10通过使lncRNA HAR1A转录失活来抑制SMARCD1介导的iNOS激活，从而缓解狼疮肾炎。

IF 3.3 4区医学

Autoimmunity Pub Date : 2024-12-01 Epub Date: 2024-11-05 DOI: 10.1080/08916934.2024.2423758

Ya Liu, Pei Li, Longkun Wang, Luojia Jiang, Zhengfu Li, Yu Mei, Weijuan Deng

{"title":"iTreg cells-secreted IL10 alleviates lupus nephritis through inactivating lncRNA HAR1A transcription to suppress SMARCD1-mediated iNOS activation.","authors":"Ya Liu, Pei Li, Longkun Wang, Luojia Jiang, Zhengfu Li, Yu Mei, Weijuan Deng","doi":"10.1080/08916934.2024.2423758","DOIUrl":"https://doi.org/10.1080/08916934.2024.2423758","url":null,"abstract":"Lupus nephritis (LN) is a highly prevalent complication of systemic lupus erythematosus (SLE). Long non-coding RNAs (lncRNAs) are essential modulators in multiple types of human diseases, including LN. In the current study, we searched on online GEO database to select out lncRNAs that were differentially expressed in blood samples of LN patients. Through further RT-qPCR analysis, we found that lncRNA Highly Accelerated Region 1 A (HAR1A) is most significantly upregulated in blood samples of LN patients. Functionally, we detected that overexpression of HAR1A could aggravate LPS-induced injury and inflammation. According to the results of bioinformatics analysis and mechanism experiments, we determined that HAR1A binds with miR-149-3p to upregulate SMARCD1 through competing endogenous RNA (ceRNA) mechanism. It has been proven that iNOS is an inflammation inducer. Here, we found that HAR1A/miR-149-3p/SMARCD1 upregulates iNOS expression through enhancing H3K27ac level in iNOS promoter. Previously, we proved that CD8+CD103+ iTreg cells could alleviate glomerular endothelial cell injury. Moreover, we demonstrated that CD8 + CD103+ iTreg cells-secreted IL-10 downregulated HAR1A expression by impeding NF-κB pathway activation. In conclusion, this study provides evidences revealing a novel molecular pathway blocked by CD8+CD103+ iTreg cells in LN.","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2423758"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581953","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}

引用次数: 0

Bioinformatics and systems-biology approach to identify common pathogenic mechanisms for COVID-19 and systemic lupus erythematosus. 通过生物信息学和系统生物学方法确定 COVID-19 和系统性红斑狼疮的共同致病机制。

IF 3.5 4区医学

Autoimmunity Pub Date : 2024-12-01 Epub Date: 2024-02-08 DOI: 10.1080/08916934.2024.2304826

Yinlan Wu, Yanhong Li, Yu Zhou, Xiufeng Bai, Yi Liu

{"title":"Bioinformatics and systems-biology approach to identify common pathogenic mechanisms for COVID-19 and systemic lupus erythematosus.","authors":"Yinlan Wu, Yanhong Li, Yu Zhou, Xiufeng Bai, Yi Liu","doi":"10.1080/08916934.2024.2304826","DOIUrl":"10.1080/08916934.2024.2304826","url":null,"abstract":"Background: The Coronavirus disease 2019 (COVID-19) pandemic has brought a heavy burden to the world, interestingly, it shares many clinical symptoms with systemic lupus erythematosus (SLE). It is unclear whether there is a similar pathological process between COVID-9 and SLE. In addition, we don't know how to treat SLE patients with COVID-19. In this study, we analyse the potential similar pathogenesis between SLE and COVID-19 and explore their possible drug regimens using bioinformatics and systems biology approaches.Methods: The common differentially expressed genes (DEGs) were extracted from the COVID-19 datasets and the SLE datasets for functional enrichment, pathway analysis and candidate drug analysis.Result: Based on the two transcriptome datasets between COVID-19 and SLE, 325 common DEGs were selected. Hub genes were identified by protein-protein interaction (PPI) analysis. few found a variety of similar functional changes between COVID-19 and SLE, which may be related to the pathogenesis of COVID-19. Besides, we explored the related regulatory networks. Then, through drug target matching, we found many candidate drugs for patients with COVID-19 only or COVID-19 combined with SLE.Conclusion: COVID-19 and SLE patients share many common hub genes, related pathways and regulatory networks. Based on these common targets, we found many potential drugs that could be used in treating patient with COVID-19 or COVID-19 combined with SLE.","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2304826"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139705973","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}

引用次数: 0

CD5L induces inflammation and survival in RA-FLS through ERK1/2 MAPK pathway. CD5L 通过 ERK1/2 MAPK 通路诱导 RA-FLS 的炎症和存活。

IF 3.5 4区医学

Autoimmunity Pub Date : 2024-12-01 Epub Date: 2024-02-29 DOI: 10.1080/08916934.2023.2201412

Huiqing Yang, Yan Luo, Xiaofei Lai

引用次数: 0

High throughput multiplex immunoassays stratify patients according to symptom burden across the anti-Ro positive systemic autoimmune rheumatic disease spectrum. 高通量多重免疫测定可根据抗 Ro 阳性系统性自身免疫性风湿病谱系的症状负荷对患者进行分层。

IF 3.3 4区医学

Autoimmunity Pub Date : 2024-12-01 Epub Date: 2024-11-28 DOI: 10.1080/08916934.2024.2433237

Sarah Dyball, Rudresh Shukla, Anastasia-Vasiliki Madenidou, Maya H Buch, Ian N Bruce, Ben Parker

{"title":"High throughput multiplex immunoassays stratify patients according to symptom burden across the anti-Ro positive systemic autoimmune rheumatic disease spectrum.","authors":"Sarah Dyball, Rudresh Shukla, Anastasia-Vasiliki Madenidou, Maya H Buch, Ian N Bruce, Ben Parker","doi":"10.1080/08916934.2024.2433237","DOIUrl":"https://doi.org/10.1080/08916934.2024.2433237","url":null,"abstract":"Anti-Ro/SS-A antibodies are prevalent across systemic autoimmune rheumatic diseases (SARDs) and may signify a distinctive phenotype. This study aimed to identify protein biomarkers associated with symptom burden and health-related quality of life (HR-QoL), and use protein-based stratification to identify clinically meaningful clusters and inflammatory pathways implicated. Anti-Ro positive SARD patients were enrolled in a 6-month pilot study. HR-QoL was determined using a patient-reported visual analogue scale, and symptom burden was assessed with the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI). Proximity extension immunoassays measured normalized protein expression (NPX) across 92 inflammatory proteins. Linear regression identified proteins linked to patient outcomes. Unsupervised hierarchical clustering of baseline NPX identified patient clusters. Functional protein association networks were visualized using String V.12.0. Diagnostic groups showed no differences in HR-QoL or physician global assessment (PhGA). Poor HR-QoL and high symptom burden correlated with downregulated inflammatory proteins, while PhGA correlated with upregulated proteins. Two distinct clusters were identified; Cluster 1, 'low expression cluster' exhibited higher symptom burden and more impaired HR-QoL, while Cluster 2, 'high expression cluster' correlated with a higher physician global assessment (PhGA). Key hub proteins included TGF-β1, CXCL-8, and CCL-2. This study identified patient clusters across the Ro-positive SARD, linking symptom burden to specific proteomic profiles. Unraveling novel protein networks associated with symptom burden and poor HR-QoL may identify therapeutic targets, which address patient-reported outcome measures (PROMs) across several disease indications.","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2433237"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738277","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}

引用次数: 0

HLA-transgenic mouse models to study autoimmune central nervous system diseases. 研究自身免疫性中枢神经系统疾病的 HLA 转基因小鼠模型。

IF 3.3 4区医学

Autoimmunity Pub Date : 2024-12-01 Epub Date: 2024-08-21 DOI: 10.1080/08916934.2024.2387414

Kyle R Pressley, Lance Schwegman, Maria Montes De Oca Arena, Carol Chase Huizar, Scott S Zamvil, Thomas G Forsthuber

{"title":"HLA-transgenic mouse models to study autoimmune central nervous system diseases.","authors":"Kyle R Pressley, Lance Schwegman, Maria Montes De Oca Arena, Carol Chase Huizar, Scott S Zamvil, Thomas G Forsthuber","doi":"10.1080/08916934.2024.2387414","DOIUrl":"10.1080/08916934.2024.2387414","url":null,"abstract":"It is known that certain human leukocyte antigen (HLA) genes are associated with autoimmune central nervous system (CNS) diseases, such as multiple sclerosis (MS), but their exact role in disease susceptibility and etiopathogenesis remains unclear. The best studied HLA-associated autoimmune CNS disease is MS, and thus will be the primary focus of this review. Other HLA-associated autoimmune CNS diseases, such as autoimmune encephalitis and neuromyelitis optica will be discussed. The lack of animal models to accurately capture the complex human autoimmune response remains a major challenge. HLA transgenic (tg) mice provide researchers with powerful tools to investigate the underlying mechanisms promoting susceptibility and progression of HLA-associated autoimmune CNS diseases, as well as for elucidating the myelin epitopes potentially targeted by T cells in autoimmune disease patients. We will discuss the potential role(s) of autoimmune disease-associated HLA alleles in autoimmune CNS diseases and highlight information provided by studies using HLA tg mice to investigate the underlying pathological mechanisms and opportunities to use these models for development of novel therapies.","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2387414"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Animal models of immune-mediated demyelinating polyneuropathies. 免疫介导的脱髓鞘性多发性神经病的动物模型。

IF 3.3 4区医学

Autoimmunity Pub Date : 2024-12-01 Epub Date: 2024-06-08 DOI: 10.1080/08916934.2024.2361745

Eroboghene E Ubogu

{"title":"Animal models of immune-mediated demyelinating polyneuropathies.","authors":"Eroboghene E Ubogu","doi":"10.1080/08916934.2024.2361745","DOIUrl":"10.1080/08916934.2024.2361745","url":null,"abstract":"Immune-mediated demyelinating polyneuropathies (IMDPs) are rare disorders in which dysregulated adaptive immune responses cause peripheral nerve demyelinating inflammation and axonal injury in susceptible individuals. Despite significant advances in understanding IMDP pathogenesis guided by patient data and representative mammalian models, specific therapies are lacking. Significant knowledge gaps in IMDP pathogenesis still exist, e.g. precise antigen(s) and mechanisms that initially trigger immune system activation and identification of large population disease susceptibility factors. The initial directional cues for antigen-specific effector or autoreactive leukocyte trafficking into peripheral nerves are also unknown. An overview of current animal models, with emphasis on the experimental autoimmune neuritis and spontaneous autoimmune peripheral polyneuropathy models, is provided. Insights on the initial directional cues for peripheral nerve tissue specific autoimmunity using a novel Major Histocompatibility Complex class II conditional knockout mouse strain are also discussed, suggesting an essential research tool to study cell- and time-dependent adaptive immunity in autoimmune diseases.","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2361745"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Osteocyte-derived exosomes regulate the DLX2/wnt pathway to alleviate osteoarthritis by mediating cartilage repair. 骨细胞源性外泌体调节 DLX2/wnt 通路，通过介导软骨修复缓解骨关节炎。

IF 3.3 4区医学

Autoimmunity Pub Date : 2024-12-01 Epub Date: 2024-07-01 DOI: 10.1080/08916934.2024.2364686

Wenjuan Xu, Yuanyuan Zhang, Lijuan Li, Liyan Pan, Li Lu, Shenshen Zhi, Wei Li

{"title":"Osteocyte-derived exosomes regulate the DLX2/wnt pathway to alleviate osteoarthritis by mediating cartilage repair.","authors":"Wenjuan Xu, Yuanyuan Zhang, Lijuan Li, Liyan Pan, Li Lu, Shenshen Zhi, Wei Li","doi":"10.1080/08916934.2024.2364686","DOIUrl":"10.1080/08916934.2024.2364686","url":null,"abstract":"Background: Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA.Objective: This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms.Methods: An injury cell model was established by treating chondrocytes with IL-1β. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 in vivo.Results: Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2.Conclusion: Osteocyte-derived exosomal DLX2 alleviated IL-1β-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2364686"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465883","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}

引用次数: 0

Subchronic intranasal lipopolysaccharide exposure induces pulmonary autoimmunity and glomerulonephritis in NZBWF1 mice. 亚慢性鼻内脂多糖暴露诱导 NZBWF1 小鼠肺部自身免疫和肾小球肾炎。

IF 3.3 4区医学

Autoimmunity Pub Date : 2024-12-01 Epub Date: 2024-07-08 DOI: 10.1080/08916934.2024.2370536

Lauren K Heine, Lichchavi D Rajasinghe, James G Wagner, Ryan P Lewandowski, Quan-Zhen Li, Alexa L Richardson, Ashleigh N Tindle, Jenan J Shareef, Jack R Harkema, James J Pestka

{"title":"Subchronic intranasal lipopolysaccharide exposure induces pulmonary autoimmunity and glomerulonephritis in NZBWF1 mice.","authors":"Lauren K Heine, Lichchavi D Rajasinghe, James G Wagner, Ryan P Lewandowski, Quan-Zhen Li, Alexa L Richardson, Ashleigh N Tindle, Jenan J Shareef, Jack R Harkema, James J Pestka","doi":"10.1080/08916934.2024.2370536","DOIUrl":"10.1080/08916934.2024.2370536","url":null,"abstract":"Lupus, a systemic autoimmune disease shaped by gene-environment interplay, often progresses to endstage renal failure. While subchronic systemic exposure to bacterial lipopolysaccharide (LPS) triggers autoimmunity and glomerulonephritis in lupus-prone mice, it is unknown if inhaling LPS, which is common in certain occupations, can similarly trigger lupus. Here we determined how subchronic intranasal (IN) LPS instillation influences autoimmunity and glomerulonephritis development in lupusprone NZBWF1 female mice. Briefly, mice were IN-instilled with vehicle or E. coli LPS (0.8 μg/g) twice weekly for 5 wk, followed by necropsy. For systemic comparison, additional cohorts of mice were injected with LPS intraperitoneally (IP) using identical doses/timing. Lungs were assessed for inflammatory and autoimmune responses and then related to systemic autoimmunity and glomerulonephritis. IN/LPS exposure induced in the lung: i) leukocyte infiltration, ii)mRNA signatures for cytokines, chemokines, IFN-regulated, and cell death-related genes, iii) ectopic lymphoid tissue formation, and iv)diverse IgM and IgG autoantibodies (AAbs). Pulmonary effects coincided with enlarged spleens, elevated plasma IgG AAbs, and inflamed IgG-containing kidney glomeruli. In contrast, IP/LPS treatment induced systemic autoimmunity and glomerulonephritis without pulmonary manifestations. Taken together, these preclinical findings suggest the lung could serve as a critical nexus for triggering autoimmunity by respirable LPS in genetically predisposed individuals.","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2370536"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0