{"title":"单核细胞/巨噬细胞来源的NLRP3通过nod样受体途径促进强直性脊柱炎的发生和进展。","authors":"Jiarui Chen, Chengqian Huang, Tianyou Chen, Sitan Feng, Jiang Xue, Zhongxian Zhou, Shengsheng Huang, Tuo Liang, Rongqing He, Boli Qin, Xiaopeng Qin, Sen Mo, Chenxing Zhou, Shaofeng Wu, Wendi Wei, Hao Li, Zhaojun Lu, Yingying Qin, Shian Liao, Liyi Chen, Xinli Zhan, Chong Liu","doi":"10.1007/s10875-025-01961-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease primarily affecting the axial skeleton. Despite significant advances, its pathogenic mechanisms remain unclear, posing challenges to early diagnosis and effective treatment. This study aims to elucidate the pathogenic pathways of AS and explore potential therapeutic strategies.</p><p><strong>Methods: </strong>Blood routine test results from AS and non-AS patients were collected, and t-tests and logistic regression analyses were performed on blood cell count parameters. Key findings from the blood tests were validated using GEO transcriptomic datasets. Single-cell data from GEO were then used to conduct in-depth analyses of immune cell subsets and their functions. To validate findings, single-cell sequencing was performed on bone marrow samples collected from AS and fracture control patients, followed by pathway analysis through GSEA. Finally, upstream regulatory mechanisms and potential therapeutic agents were investigated.</p><p><strong>Results: </strong>This study identified a classical monocyte-macrophage-inflammatory macrophage differentiation trajectory in AS, demonstrating that monocytes/macrophages play a critical role in AS pathogenesis via the NOD-like receptor signaling pathway, primarily mediated by NLRP3. Several regulatory factors, including hsa-miR-3682-3p, AR, IRF4, MYB, RUNX1, and TAL1, were found to modulate NLRP3 expression. Additionally, various chemical compounds, anticancer drugs, and cinnamaldehyde were identified as potential therapeutic agents targeting NLRP3.</p><p><strong>Conclusion: </strong>In AS, the classical monocyte-macrophage-inflammatory macrophage differentiation pathway is enhanced, with monocyte/macrophage-derived NLRP3 driving disease progression via the NOD-like receptor signaling pathway. Regulatory factors and potential therapeutic agents targeting NLRP3 were identified, offering new insights into AS pathogenesis and therapeutic strategies.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":"169"},"PeriodicalIF":4.1000,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12689755/pdf/","citationCount":"0","resultStr":"{\"title\":\"Monocyte/macrophage-derived NLRP3 Promotes the Onset and Progression of Ankylosing Spondylitis Via the NOD-like Receptor Pathway.\",\"authors\":\"Jiarui Chen, Chengqian Huang, Tianyou Chen, Sitan Feng, Jiang Xue, Zhongxian Zhou, Shengsheng Huang, Tuo Liang, Rongqing He, Boli Qin, Xiaopeng Qin, Sen Mo, Chenxing Zhou, Shaofeng Wu, Wendi Wei, Hao Li, Zhaojun Lu, Yingying Qin, Shian Liao, Liyi Chen, Xinli Zhan, Chong Liu\",\"doi\":\"10.1007/s10875-025-01961-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease primarily affecting the axial skeleton. Despite significant advances, its pathogenic mechanisms remain unclear, posing challenges to early diagnosis and effective treatment. This study aims to elucidate the pathogenic pathways of AS and explore potential therapeutic strategies.</p><p><strong>Methods: </strong>Blood routine test results from AS and non-AS patients were collected, and t-tests and logistic regression analyses were performed on blood cell count parameters. Key findings from the blood tests were validated using GEO transcriptomic datasets. Single-cell data from GEO were then used to conduct in-depth analyses of immune cell subsets and their functions. To validate findings, single-cell sequencing was performed on bone marrow samples collected from AS and fracture control patients, followed by pathway analysis through GSEA. Finally, upstream regulatory mechanisms and potential therapeutic agents were investigated.</p><p><strong>Results: </strong>This study identified a classical monocyte-macrophage-inflammatory macrophage differentiation trajectory in AS, demonstrating that monocytes/macrophages play a critical role in AS pathogenesis via the NOD-like receptor signaling pathway, primarily mediated by NLRP3. Several regulatory factors, including hsa-miR-3682-3p, AR, IRF4, MYB, RUNX1, and TAL1, were found to modulate NLRP3 expression. Additionally, various chemical compounds, anticancer drugs, and cinnamaldehyde were identified as potential therapeutic agents targeting NLRP3.</p><p><strong>Conclusion: </strong>In AS, the classical monocyte-macrophage-inflammatory macrophage differentiation pathway is enhanced, with monocyte/macrophage-derived NLRP3 driving disease progression via the NOD-like receptor signaling pathway. Regulatory factors and potential therapeutic agents targeting NLRP3 were identified, offering new insights into AS pathogenesis and therapeutic strategies.</p>\",\"PeriodicalId\":15531,\"journal\":{\"name\":\"Journal of Clinical Immunology\",\"volume\":\" \",\"pages\":\"169\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-11-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12689755/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10875-025-01961-4\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10875-025-01961-4","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Monocyte/macrophage-derived NLRP3 Promotes the Onset and Progression of Ankylosing Spondylitis Via the NOD-like Receptor Pathway.
Background and objectives: Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease primarily affecting the axial skeleton. Despite significant advances, its pathogenic mechanisms remain unclear, posing challenges to early diagnosis and effective treatment. This study aims to elucidate the pathogenic pathways of AS and explore potential therapeutic strategies.
Methods: Blood routine test results from AS and non-AS patients were collected, and t-tests and logistic regression analyses were performed on blood cell count parameters. Key findings from the blood tests were validated using GEO transcriptomic datasets. Single-cell data from GEO were then used to conduct in-depth analyses of immune cell subsets and their functions. To validate findings, single-cell sequencing was performed on bone marrow samples collected from AS and fracture control patients, followed by pathway analysis through GSEA. Finally, upstream regulatory mechanisms and potential therapeutic agents were investigated.
Results: This study identified a classical monocyte-macrophage-inflammatory macrophage differentiation trajectory in AS, demonstrating that monocytes/macrophages play a critical role in AS pathogenesis via the NOD-like receptor signaling pathway, primarily mediated by NLRP3. Several regulatory factors, including hsa-miR-3682-3p, AR, IRF4, MYB, RUNX1, and TAL1, were found to modulate NLRP3 expression. Additionally, various chemical compounds, anticancer drugs, and cinnamaldehyde were identified as potential therapeutic agents targeting NLRP3.
Conclusion: In AS, the classical monocyte-macrophage-inflammatory macrophage differentiation pathway is enhanced, with monocyte/macrophage-derived NLRP3 driving disease progression via the NOD-like receptor signaling pathway. Regulatory factors and potential therapeutic agents targeting NLRP3 were identified, offering new insights into AS pathogenesis and therapeutic strategies.
期刊介绍：
The Journal of Clinical Immunology publishes impactful papers in the realm of human immunology, delving into the diagnosis, pathogenesis, prognosis, or treatment of human diseases. The journal places particular emphasis on primary immunodeficiencies and related diseases, encompassing inborn errors of immunity in a broad sense, their underlying genotypes, and diverse phenotypes. These phenotypes include infection, malignancy, allergy, auto-inflammation, and autoimmunity. We welcome a broad spectrum of studies in this domain, spanning genetic discovery, clinical description, immunologic assessment, diagnostic approaches, prognosis evaluation, and treatment interventions. Case reports are considered if they are genuinely original and accompanied by a concise review of the relevant medical literature, illustrating how the novel case study advances the field. The instructions to authors provide detailed guidance on the four categories of papers accepted by the journal.
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