Autoimmunity最新文献

{"title":"Identification of macrophage-related molecular subgroups and risk signature in colorectal cancer based on a bioinformatics analysis.","authors":"Qi Liu, Li Liao","doi":"10.1080/08916934.2024.2321908","DOIUrl":"10.1080/08916934.2024.2321908","url":null,"abstract":"<p><p>Macrophages play a crucial role in tumor initiation and progression, while macrophage-associated gene signature in colorectal cancer (CRC) patients has not been investigated. Our study aimed to identify macrophage-related molecular subgroups and develop a macrophage-related risk model to predict CRC prognosis. The mRNA expression profile and clinical information of CRC patients were obtained from TCGA and GEO databases. CRC patients from TCGA were divided into high and low macrophage subgroups based on the median macrophage score. The ESTIMATE and CIBERSORT algorithms were used to assess immune cell infiltration between subgroups. GSVA and GSEA analyses were performed to investigate differences in enriched pathways between subgroups. Univariate and LASSO Cox regression were used to build a prognostic risk model, which was further validated in the GSE39582 dataset. A high macrophage score subgroup was associated with poor prognosis, highly activated immune-related pathways and an immune-active microenvironment. A total of 547 differentially expressed macrophage-related genes (DEMRGs) were identified, among which seven genes (including RIMKLB, UST, PCOLCE2, ZNF829, TMEM59L, CILP2, DTNA) were identified by COX regression analyses and used to build a risk score model. The risk model shows good predictive and diagnostic values for CRC patients in both TCGA and GSE39852 datasets. Furthermore, multivariate Cox regression analysis showed that the risk score was an independent risk factor for overall survival in CRC patients. Our findings provided a novel insight into macrophage heterogeneity and its immunological role in CRC. This risk score model may serve as an effective prognostic tool and contribute to personalised clinical management of CRC patients.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2321908"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093306","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":"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":"<p><p>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.</p>","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}

{"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":"<p><strong>Background: </strong>Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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 <i>in vivo</i>.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","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}

{"title":"The association of 25(OH)D, interleukin-4, interleukin-5, and interleukin-13 levels with the burden of soil-transmitted helminth infection in stunted children aged 24-59 months.","authors":"Riyadi Adrizain, Monika Verena Nagari, Djatnika Setiabudi, Afiat Berbudi, Budi Setiabudiawan","doi":"10.1080/08916934.2024.2330394","DOIUrl":"10.1080/08916934.2024.2330394","url":null,"abstract":"<p><p>Soil-transmitted helminth (STH) among children aged 24-59 months is one cause of chronic infection that could lead to stunting. The association of 25(OH)D and immune responses during chronic infection in stunted populations has not yet been well established. An association study of case-control data was conducted in Bandung district from October 2019 to January 2023. Sociodemographic factors, stool samples, and serum levels of 25(OH)D, interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) were assessed. Statistical analysis was performed to evaluate the prevalence and association of 25(OH)D, IL-4, IL-5, and IL-13 with the burden of STH infection in stunted children. In total, 401 stunted children were recruited. A higher burden of STH infection was found for lower levels of IL-5 (<i>r</i> = -0.477; <i>p</i> = 0.004) and IL-13 (<i>r</i> = -0.433; <i>p</i> = 0.028). Thus, 25(OH)D, IL-4, IL-5, and IL-13 play a role in the burden of STH infection.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2330394"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142657","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":"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":"<p><p>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.</p>","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}

{"title":"Genome-wide identification of cell type-specific susceptibility genes for Juvenile dermatomyositis through the analysis of N⁶-methyladenosine-associated SNPs.","authors":"Huan Zhang, Kedi Fan, Zhentao Zhang, Yufan Guo, Xingbo Mo","doi":"10.1080/08916934.2024.2419117","DOIUrl":"10.1080/08916934.2024.2419117","url":null,"abstract":"<p><p>Genome-wide association studies (GWASs) have pinpointed genetic loci associated with juvenile dermatomyositis (JDM). Functional genes within the GWAS loci may be cell type-specific, but their identity remains largely unknown. N⁶-methyladenosine (m⁶A) plays a pivotal role in regulating various cellular processes and is linked to autoimmune diseases. This study aimed to underscore the potential functional genes within the GWAS loci through the analysis of m⁶A-associated SNPs (m⁶A-SNPs), specifically within relevant cell types. JDM-associated m⁶A-SNPs were identified from the GWAS summary dataset. The correlation between m⁶A-SNPs and gene expression was assessed through bulk tissue and single-cell eQTL analyses. To further investigate the relationship between gene expression and JDM, Mendelian randomization analysis was employed. Additionally, differential expression analyses were conducted on bulk tissues, as well as single-cell transcriptomic data comprising 6 JDM patients and 11 juvenile controls (99,396 cells). Seven m⁶A-SNPs associated with JDM were identified. Bulk tissue analysis revealed differential expression of <i>HLA-DPA1</i>, <i>HLA-DPB1</i>, <i>MICB</i>, <i>HLA-A</i>, <i>HLA-F</i>, <i>HLA-DQB2</i>, <i>HLA-DRB5</i>, <i>TAP2</i>, <i>PSMB9</i>, <i>MICA</i>, <i>AIF1</i>, and <i>DDX39B</i> influenced by m⁶A-SNPs, all showing associations with JDM in both differential expression and Mendelian randomization analyses. In single-cell analysis, the six m⁶A-SNPs within the HLA locus acted as cell-type-specific eQTLs, correlating with the expression of <i>HLA-A</i>, <i>HLA-B</i>, <i>HLA-C</i>, <i>HLA-DPB1</i>, <i>HLA-DQA1</i>, <i>HLA-DQB1</i> and <i>HLA-DRB1</i> in myeloid, T or B cells. Notably, these genes displayed abnormal expression in T, B, and myeloid cells of JDM patients. The present study identified m⁶A-SNPs within JDM susceptibility genes, shedding light on the intricate interplay between m⁶A-SNPs, gene expression, and JDM.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2419117"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493756","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":"Animal models of lupus nephritis: the past, present and a future outlook.","authors":"Divya Katikaneni, Laurence Morel, Yogesh Scindia","doi":"10.1080/08916934.2024.2319203","DOIUrl":"10.1080/08916934.2024.2319203","url":null,"abstract":"<p><p>Lupus nephritis (LN) is the most severe end-organ pathology in Systemic Lupus Erythematosus (SLE). Research has enhanced our understanding of immune effectors and inflammatory pathways in LN. However, even with the best available therapy, the rate of complete remission for proliferative LN remains below 50%. A deeper understanding of the resistance or susceptibility of renal cells to injury during the progression of SLE is critical for identifying new targets and developing effective long-term therapies. The complex and heterogeneous nature of LN, combined with the limitations of clinical research, make it challenging to investigate the aetiology of this disease directly in patients. Hence, multiple murine models resembling SLE-driven nephritis are utilised to dissect LN's cellular and genetic mechanisms, identify therapeutic targets, and screen novel compounds. This review discusses commonly used spontaneous and inducible mouse models that have provided insights into pathogenic mechanisms and long-term maintenance therapies in LN.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2319203"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10981450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140108985","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}

{"title":"The role of gut microbiota in different murine models of systemic lupus erythematosus.","authors":"Ran Lu, Xin M Luo","doi":"10.1080/08916934.2024.2378876","DOIUrl":"10.1080/08916934.2024.2378876","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune system dysfunction that can lead to serious health issues and mortality. Recent investigations highlight the role of gut microbiota alterations in modulating inflammation and disease severity in SLE. This review specifically summaries the variations in gut microbiota composition across various murine models of lupus. By focusing on these differences, we aim to elucidate the intricate relationship between gut microbiota dysbiosis and the development and progression of SLE in preclinical settings.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2378876"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625847","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":"<i>FOXO3</i> as a potential diagnostic biomarker for autophagy in rheumatoid arthritis: A bioinformatics study.","authors":"Qian Deng, Zining Peng, Fanyu Meng, Wangxin Zeng, Mengyuan Zhu, Nian Liu, Weitian Yan, Jiangyun Peng","doi":"10.1080/08916934.2024.2423759","DOIUrl":"10.1080/08916934.2024.2423759","url":null,"abstract":"<p><p>This study aimed to identify genes associated with autophagy and potential diagnostic biomarkers by comparing the gene expression profiles of synovial tissues in patients with rheumatoid arthritis (RA) and healthy individuals, aiming to offer new insights for clinical treatment strategies. We used publicly available datasets to analyze differentially expressed genes (DEGs) between the synovial tissue of RA patients and healthy individuals. Then, we intersected these DEGs with autophagy-related genes to identify autophagy genes in the synovial tissue of RA patients. We further analyzed the biological processes and functions of these genes. Furthermore, we used machine learning to identify characteristic autophagy genes in RA synovial tissue. Finally, we examined the differential expression of these characteristic genes in the blood of RA patients using an external dataset. Our study identified <i>FOXO3</i> as a potential biomarker for diagnosing RA. <i>FOXO3</i> gene expression was downregulated in both the synovial tissue and blood of RA patients, suggesting its involvement in multiple biological processes such as local inflammation, oxidative stress, metabolic processes, and immune responses. Our findings suggest that <i>FOXO3</i> may be a novel biomarker for the clinical diagnosis of RA and may play a crucial role in the pathogenesis of RA. The study provides new insights into the molecular mechanisms of RA and potential new therapeutic targets.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2423759"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575142","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":"Animal models of neuropsychiatric systemic lupus erythematosus: deciphering the complexity and guiding therapeutic development.","authors":"Baruh Polis, Carla M Cuda, Chaim Putterman","doi":"10.1080/08916934.2024.2330387","DOIUrl":"10.1080/08916934.2024.2330387","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) poses formidable challenges due to its multifaceted etiology while impacting multiple tissues and organs and displaying diverse clinical manifestations. Genetic and environmental factors contribute to SLE complexity, with relatively limited approved therapeutic options. Murine models offer insights into SLE pathogenesis but do not always replicate the nuances of human disease. This review critically evaluates spontaneous and induced animal models, emphasizing their validity and relevance to neuropsychiatric SLE (NPSLE). While these models undoubtedly contribute to understanding disease pathophysiology, discrepancies persist in mimicking some NPSLE intricacies. The lack of literature addressing this issue impedes therapeutic progress. We underscore the urgent need for refining models that truly reflect NPSLE complexities to enhance translational fidelity. We encourage a comprehensive, creative translational approach for targeted SLE interventions, balancing scientific progress with ethical considerations to eventually improve the management of NPSLE patients. A thorough grasp of these issues informs researchers in designing experiments, interpreting results, and exploring alternatives to advance NPSLE research.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2330387"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331540","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}