ResearchIn-Press Preview Open Access | 10.1172/jci.insight.176963
1Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, United States of America
2Aarhus University, Aarhus University, Aarhus, Denmark
3CoLabs, UCSF, San Francisco, United States of America
4Graduate Program in Biological and Medical Informatics, UCSF, San Francisco, United States of America
5Division of Rheumatology, UCSF, San Franscisco, United States of America
6Division of Pediatric Rheumatology, UCSF, San Franscisco, United States of America
7Division of Pediatric Rheumatology, UCSF, San Francisco, United States of America
8Department of Pharmaceutical Chemistry, UCSF, San Francisco, United States of America
9Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
Find articles by Rabadam, G. in: JCI | PubMed | Google Scholar
1Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, United States of America
2Aarhus University, Aarhus University, Aarhus, Denmark
3CoLabs, UCSF, San Francisco, United States of America
4Graduate Program in Biological and Medical Informatics, UCSF, San Francisco, United States of America
5Division of Rheumatology, UCSF, San Franscisco, United States of America
6Division of Pediatric Rheumatology, UCSF, San Franscisco, United States of America
7Division of Pediatric Rheumatology, UCSF, San Francisco, United States of America
8Department of Pharmaceutical Chemistry, UCSF, San Francisco, United States of America
9Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
Find articles by Wibrand, C. in: JCI | PubMed | Google Scholar
1Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, United States of America
2Aarhus University, Aarhus University, Aarhus, Denmark
3CoLabs, UCSF, San Francisco, United States of America
4Graduate Program in Biological and Medical Informatics, UCSF, San Francisco, United States of America
5Division of Rheumatology, UCSF, San Franscisco, United States of America
6Division of Pediatric Rheumatology, UCSF, San Franscisco, United States of America
7Division of Pediatric Rheumatology, UCSF, San Francisco, United States of America
8Department of Pharmaceutical Chemistry, UCSF, San Francisco, United States of America
9Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
Find articles by Flynn, E. in: JCI | PubMed | Google Scholar
1Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, United States of America
2Aarhus University, Aarhus University, Aarhus, Denmark
3CoLabs, UCSF, San Francisco, United States of America
4Graduate Program in Biological and Medical Informatics, UCSF, San Francisco, United States of America
5Division of Rheumatology, UCSF, San Franscisco, United States of America
6Division of Pediatric Rheumatology, UCSF, San Franscisco, United States of America
7Division of Pediatric Rheumatology, UCSF, San Francisco, United States of America
8Department of Pharmaceutical Chemistry, UCSF, San Francisco, United States of America
9Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
Find articles by Hartoularos, G. in: JCI | PubMed | Google Scholar
1Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, United States of America
2Aarhus University, Aarhus University, Aarhus, Denmark
3CoLabs, UCSF, San Francisco, United States of America
4Graduate Program in Biological and Medical Informatics, UCSF, San Francisco, United States of America
5Division of Rheumatology, UCSF, San Franscisco, United States of America
6Division of Pediatric Rheumatology, UCSF, San Franscisco, United States of America
7Division of Pediatric Rheumatology, UCSF, San Francisco, United States of America
8Department of Pharmaceutical Chemistry, UCSF, San Francisco, United States of America
9Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
Find articles by Sun, Y. in: JCI | PubMed | Google Scholar
1Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, United States of America
2Aarhus University, Aarhus University, Aarhus, Denmark
3CoLabs, UCSF, San Francisco, United States of America
4Graduate Program in Biological and Medical Informatics, UCSF, San Francisco, United States of America
5Division of Rheumatology, UCSF, San Franscisco, United States of America
6Division of Pediatric Rheumatology, UCSF, San Franscisco, United States of America
7Division of Pediatric Rheumatology, UCSF, San Francisco, United States of America
8Department of Pharmaceutical Chemistry, UCSF, San Francisco, United States of America
9Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
Find articles by Madubata, C. in: JCI | PubMed | Google Scholar
1Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, United States of America
2Aarhus University, Aarhus University, Aarhus, Denmark
3CoLabs, UCSF, San Francisco, United States of America
4Graduate Program in Biological and Medical Informatics, UCSF, San Francisco, United States of America
5Division of Rheumatology, UCSF, San Franscisco, United States of America
6Division of Pediatric Rheumatology, UCSF, San Franscisco, United States of America
7Division of Pediatric Rheumatology, UCSF, San Francisco, United States of America
8Department of Pharmaceutical Chemistry, UCSF, San Francisco, United States of America
9Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
Find articles by Fragiadakis, G. in: JCI | PubMed | Google Scholar |
1Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, United States of America
2Aarhus University, Aarhus University, Aarhus, Denmark
3CoLabs, UCSF, San Francisco, United States of America
4Graduate Program in Biological and Medical Informatics, UCSF, San Francisco, United States of America
5Division of Rheumatology, UCSF, San Franscisco, United States of America
6Division of Pediatric Rheumatology, UCSF, San Franscisco, United States of America
7Division of Pediatric Rheumatology, UCSF, San Francisco, United States of America
8Department of Pharmaceutical Chemistry, UCSF, San Francisco, United States of America
9Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
Find articles by Ye, J. in: JCI | PubMed | Google Scholar
1Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, United States of America
2Aarhus University, Aarhus University, Aarhus, Denmark
3CoLabs, UCSF, San Francisco, United States of America
4Graduate Program in Biological and Medical Informatics, UCSF, San Francisco, United States of America
5Division of Rheumatology, UCSF, San Franscisco, United States of America
6Division of Pediatric Rheumatology, UCSF, San Franscisco, United States of America
7Division of Pediatric Rheumatology, UCSF, San Francisco, United States of America
8Department of Pharmaceutical Chemistry, UCSF, San Francisco, United States of America
9Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
Find articles by Kim, S. in: JCI | PubMed | Google Scholar |
1Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, United States of America
2Aarhus University, Aarhus University, Aarhus, Denmark
3CoLabs, UCSF, San Francisco, United States of America
4Graduate Program in Biological and Medical Informatics, UCSF, San Francisco, United States of America
5Division of Rheumatology, UCSF, San Franscisco, United States of America
6Division of Pediatric Rheumatology, UCSF, San Franscisco, United States of America
7Division of Pediatric Rheumatology, UCSF, San Francisco, United States of America
8Department of Pharmaceutical Chemistry, UCSF, San Francisco, United States of America
9Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
Find articles by Gartner, Z. in: JCI | PubMed | Google Scholar |
1Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, United States of America
2Aarhus University, Aarhus University, Aarhus, Denmark
3CoLabs, UCSF, San Francisco, United States of America
4Graduate Program in Biological and Medical Informatics, UCSF, San Francisco, United States of America
5Division of Rheumatology, UCSF, San Franscisco, United States of America
6Division of Pediatric Rheumatology, UCSF, San Franscisco, United States of America
7Division of Pediatric Rheumatology, UCSF, San Francisco, United States of America
8Department of Pharmaceutical Chemistry, UCSF, San Francisco, United States of America
9Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
Find articles by Sirota, M. in: JCI | PubMed | Google Scholar |
1Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, United States of America
2Aarhus University, Aarhus University, Aarhus, Denmark
3CoLabs, UCSF, San Francisco, United States of America
4Graduate Program in Biological and Medical Informatics, UCSF, San Francisco, United States of America
5Division of Rheumatology, UCSF, San Franscisco, United States of America
6Division of Pediatric Rheumatology, UCSF, San Franscisco, United States of America
7Division of Pediatric Rheumatology, UCSF, San Francisco, United States of America
8Department of Pharmaceutical Chemistry, UCSF, San Francisco, United States of America
9Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
Find articles by Neely, J. in: JCI | PubMed | Google Scholar
Published May 14, 2024 - More info
Juvenile Dermatomyositis (JDM) is one of several childhood-onset autoimmune disorders characterized by a type I interferon response and autoantibodies. Treatment options are limited due to incomplete understanding of how the disease emerges from dysregulated cell states across the immune system. We therefore investigated the blood of JDM patients 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 towards 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 interferon 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, CD8+ T cells and gdT cells. Together, these findings unveil the coordinated immune dysregulation underpinning JDM and provide insight into strategies for restoring balance in immune function.