Single-cell RNA sequencing of submandibular gland reveals collagen type XV-positive fibroblasts as a disease-characterizing cell population of IgG4-related disease.
Collagen type XV
Fibroblasts
IgG4-related disease
Single-cell RNA sequence
Journal
Arthritis research & therapy
ISSN: 1478-6362
Titre abrégé: Arthritis Res Ther
Pays: England
ID NLM: 101154438
Informations de publication
Date de publication:
20 Feb 2024
20 Feb 2024
Historique:
received:
30
11
2023
accepted:
16
02
2024
medline:
21
2
2024
pubmed:
21
2
2024
entrez:
20
2
2024
Statut:
epublish
Résumé
IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with an unknown etiology, affecting single/multiple organ(s). Pathological findings include the infiltration of IgG4-producing plasma cells, obliterative phlebitis, and storiform fibrosis. Although immunological studies have shed light on the dysregulation of lymphocytes in IgG4-RD pathogenesis, the role of non-immune cells remains unclear. This study aimed to investigate the demographics and characteristics of non-immune cells in IgG4-RD and explore potential biomarkers derived from non-immune cells in the sera. We conducted single-cell RNA sequence (scRNA-seq) on non-immune cells isolated from submandibular glands of IgG4-RD patients. We focused on fibroblasts expressing collagen type XV and confirmed the presence of those fibroblasts using immunohistochemistry. Additionally, we measured the levels of collagen type XV in the sera of IgG4-RD patients. The scRNA-seq analysis revealed several distinct clusters consisting of fibroblasts, endothelial cells, ductal cells, and muscle cells. Differential gene expression analysis showed upregulation of COL15A1 in IgG4-RD fibroblasts compared to control subjects. Notably, COL15A1-positive fibroblasts exhibited a distinct transcriptome compared to COL15A1-negative counterparts. Immunohistochemical analysis confirmed a significant presence of collagen type XV-positive fibroblasts in IgG4-RD patients. Furthermore, immune-suppressive therapy in active IgG4-RD patients resulted in decreased serum levels of collagen type XV. Our findings suggest that collagen type XV-producing fibroblasts may represent a disease-characterizing non-immune cell population in IgG4-RD and hold potential as a disease-monitoring marker.
Identifiants
pubmed: 38378635
doi: 10.1186/s13075-024-03289-7
pii: 10.1186/s13075-024-03289-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
55Subventions
Organisme : Japan Society for the Promotion of Science
ID : 21K08436
Informations de copyright
© 2024. The Author(s).
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