دورية أكاديمية
Coordinated immune dysregulation in juvenile dermatomyositis revealed by single-cell genomics.
| العنوان: | Coordinated immune dysregulation in juvenile dermatomyositis revealed by single-cell genomics. |
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| المؤلفون: | Rabadam G; UC Berkeley-UC San Francisco Graduate Program in Bioengineering, and.; Department of Pharmaceutical Chemistry, UCSF, San Francisco, California, USA., Wibrand C; Aarhus University, Aarhus, Denmark.; Division of Pediatric Rheumatology, Department of Pediatrics., Flynn E; CoLabs., Hartoularos GC; Graduate Program in Biological and Medical Informatics.; Division of Rheumatology, Department of Medicine.; Institute for Human Genetics., Sun Y; Division of Rheumatology, Department of Medicine., Madubata C; Division of Pediatric Rheumatology, Department of Pediatrics.; CoLabs., Fragiadakis GK; CoLabs.; Division of Rheumatology, Department of Medicine., Ye CJ; Division of Rheumatology, Department of Medicine.; Institute for Human Genetics.; Department of Epidemiology and Biostatistics, and.; Bakar Computational Health Sciences Institute, UCSF, San Francisco, California, USA.; Chan Zuckerberg Biohub, San Francisco, California, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, California, USA., Kim S; Division of Pediatric Rheumatology, Department of Pediatrics., Gartner ZJ; Department of Pharmaceutical Chemistry, UCSF, San Francisco, California, USA.; Chan Zuckerberg Biohub, San Francisco, California, USA., Sirota M; Bakar Computational Health Sciences Institute, UCSF, San Francisco, California, USA.; Department of Pediatrics, UCSF, San Francisco, California, USA., Neely J; Division of Pediatric Rheumatology, Department of Pediatrics. |
| المصدر: | JCI insight [JCI Insight] 2024 May 14; Vol. 9 (12). Date of Electronic Publication: 2024 May 14. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | Dermatomyositis*/immunology , Dermatomyositis*/genetics , Dermatomyositis*/blood , Single-Cell Analysis*/methods, Humans ; Child ; Genomics/methods ; Male ; Female ; Interferon Type I/metabolism ; Interferon Type I/immunology ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Adolescent ; Child, Preschool ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Immunophenotyping |
| مستخلص: | Juvenile dermatomyositis (JDM) is one of several childhood-onset autoimmune disorders characterized by a type I IFN response and autoantibodies. Treatment options are limited due to an incomplete understanding of how the disease emerges from dysregulated cell states across the immune system. We therefore investigated the blood of patients with JDM at different stages of disease activity using single-cell transcriptomics paired with surface protein expression. By immunophenotyping peripheral blood mononuclear cells, we observed skewing of the B cell compartment toward an immature naive state as a hallmark of JDM at diagnosis. Furthermore, we find that these changes in B cells are paralleled by T cell signatures suggestive of Th2-mediated inflammation that persist despite disease quiescence. We applied network analysis to reveal that hyperactivation of the type I IFN response in all immune populations is coordinated with previously masked cell states including dysfunctional protein processing in CD4+ T cells and regulation of cell death programming in NK cells, CD8+ T cells, and γδ T cells. Together, these findings unveil the coordinated immune dysregulation underpinning JDM and provide insight into strategies for restoring balance in immune function. |
| التعليقات: | Update of: bioRxiv. 2023 Nov 10:2023.11.07.566033. doi: 10.1101/2023.11.07.566033. (PMID: 37986917) |
| فهرسة مساهمة: | Keywords: Autoimmune diseases; Autoimmunity; Bioinformatics; Rheumatology |
| المشرفين على المادة: | 0 (Interferon Type I) |
| تواريخ الأحداث: | Date Created: 20240514 Date Completed: 20240624 Latest Revision: 20240624 |
| رمز التحديث: | 20240624 |
| DOI: | 10.1172/jci.insight.176963 |
| PMID: | 38743491 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2379-3708 |
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| DOI: | 10.1172/jci.insight.176963 |