Arthritis Research & Therapy (Feb 2024)

Single-cell RNA sequencing of submandibular gland reveals collagen type XV-positive fibroblasts as a disease-characterizing cell population of IgG4-related disease

  • Shigeru Tanaka,
  • Takuya Yamamoto,
  • Arifumi Iwata,
  • Masahiro Kiuchi,
  • Kota Kokubo,
  • Tomohisa Iinuma,
  • Takahiro Sugiyama,
  • Toyoyuki Hanazawa,
  • Kiyoshi Hirahara,
  • Kei Ikeda,
  • Hiroshi Nakajima

DOI
https://doi.org/10.1186/s13075-024-03289-7
Journal volume & issue
Vol. 26, no. 1
pp. 1 – 8

Abstract

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Abstract Objectives 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. Methods 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. Results 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. Conclusions 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.

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