دورية أكاديمية
أعرض في EDS

Epigenetic changes in inflammatory arthritis monocytes contribute to disease and can be targeted by JAK inhibition.

التفاصيل البيبلوغرافية
العنوان: Epigenetic changes in inflammatory arthritis monocytes contribute to disease and can be targeted by JAK inhibition.
المؤلفون: Peeters JGC; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Boltjes A; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Scholman RC; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Vervoort SJ; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Coffer PJ; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Mokry M; Laboratory of Experimental Cardiology, UMC Utrecht, Utrecht University, Utrecht, The Netherlands.; Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Vastert SJ; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.; Department of Pediatric Rheumatology and Immunology, Division of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University Utrecht, The Netherlands., van Wijk F; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., van Loosdregt J; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
المصدر: Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2023 Aug 01; Vol. 62 (8), pp. 2887-2897.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 100883501 Publication Model: Print Cited Medium: Internet ISSN: 1462-0332 (Electronic) Linking ISSN: 14620324 NLM ISO Abbreviation: Rheumatology (Oxford) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford, UK : Avenel, N.J. : Oxford University Press ; Distributed by Mercury International, c1999-
مواضيع طبية MeSH: Monocytes*/metabolism , Arthritis*/metabolism, Humans ; Epigenesis, Genetic ; Synovial Fluid/metabolism ; Phenotype
مستخلص: Objectives: How the local inflammatory environment regulates epigenetic changes in the context of inflammatory arthritis remains unclear. Here we assessed the transcriptional and active enhancer profile of monocytes derived from the inflamed joints of JIA patients, a model well-suited for studying inflammatory arthritis.
Methods: RNA sequencing and H3K27me3 chromatin immunoprecipitation sequencing (ChIP-seq) were used to analyse the transcriptional and epigenetic profile, respectively, of JIA synovial fluid-derived monocytes.
Results: Synovial-derived monocytes display an activated phenotype, which is regulated on the epigenetic level. IFN signalling-associated genes are increased and epigenetically altered in synovial monocytes, indicating a driving role for IFN in establishing the local inflammatory phenotype. Treatment of synovial monocytes with the Janus-associated kinase (JAK) inhibitor ruxolitinib, which inhibits IFN signalling, transformed the activated enhancer landscape and reduced disease-associated gene expression, thereby inhibiting the inflammatory phenotype.
Conclusion: This study provides novel insights into epigenetic regulation of inflammatory arthritis patient-derived monocytes and highlights the therapeutic potential of epigenetic modulation for the treatment of inflammatory rheumatic diseases.
(© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
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فهرسة مساهمة: Keywords: JIA; autoimmunity; epigenetics; monocytes; synovium
تواريخ الأحداث: Date Created: 20230110 Date Completed: 20230803 Latest Revision: 20230804
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10396381
DOI: 10.1093/rheumatology/kead001
PMID: 36625523
قاعدة البيانات: MEDLINE
الوصف
تدمد:1462-0332
DOI:10.1093/rheumatology/kead001