Expansion of a novel population of NK cells with low ribosome expression in juvenile dermatomyositis

Juvenile dermatomyositis (JDM) is a pediatric autoimmune disease associated with characteristic rash and proximal muscle weakness. To gain insight into differential lymphocyte gene expression in JDM, peripheral blood mononuclear cells from 4 new-onset JDM patients and 4 healthy controls were sorted...

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Bibliographic Details
Published in:Frontiers in immunology 2022-10, Vol.13, p.1007022-1007022
Main Authors: Hilliard, Kinsey A, Throm, Allison A, Pingel, Jeanette T, Saucier, Nermina, Zaher, Hani S, French, Anthony R
Format: Article
Language:English
Subjects:
Adult
autoimmunity
Child
Dermatomyositis
Humans
Immunology
JDM
Killer Cells, Natural - metabolism
Leukocytes, Mononuclear - metabolism
NK cell
rheumatology
ribosome
Ribosomes - genetics
Ribosomes - metabolism
RNA, Ribosomal - genetics
RNAseq
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Summary:Juvenile dermatomyositis (JDM) is a pediatric autoimmune disease associated with characteristic rash and proximal muscle weakness. To gain insight into differential lymphocyte gene expression in JDM, peripheral blood mononuclear cells from 4 new-onset JDM patients and 4 healthy controls were sorted into highly enriched lymphocyte populations for RNAseq analysis. NK cells from JDM patients had substantially greater differentially expressed genes (273) than T (57) and B (33) cells. Upregulated genes were associated with the innate immune response and cell cycle, while downregulated genes were associated with decreased ribosomal RNA. Suppressed ribosomal RNA in JDM NK cells was validated by measuring transcription and phosphorylation levels. We confirmed a population of low ribosome expressing NK cells in healthy adults and children. This population of low ribosome NK cells was substantially expanded in 6 treatment-naïve JDM patients and was associated with decreased NK cell degranulation. The enrichment of this NK low ribosome population was completely abrogated in JDM patients with quiescent disease. Together, these data suggest NK cells are highly activated in new-onset JDM patients with an increased population of low ribosome expressing NK cells, which correlates with decreased NK cell function and resolved with control of active disease.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2022.1007022