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Single-cell RNA sequencing of submandibular gland reveals collagen type XV-positive fibroblasts as a disease-characterizing cell population of IgG4-related disease.
Tanaka, Shigeru; Yamamoto, Takuya; Iwata, Arifumi; Kiuchi, Masahiro; Kokubo, Kota; Iinuma, Tomohisa; Sugiyama, Takahiro; Hanazawa, Toyoyuki; Hirahara, Kiyoshi; Ikeda, Kei; Nakajima, Hiroshi.
Afiliação
  • Tanaka S; Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. stanaka@chiba-u.jp.
  • Yamamoto T; Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan.
  • Iwata A; Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan.
  • Kiuchi M; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Kokubo K; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Iinuma T; Department of Otorhinolaryngology/Head & Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Sugiyama T; Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan.
  • Hanazawa T; Department of Otorhinolaryngology/Head & Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Hirahara K; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Ikeda K; Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan. k-ikeda847@dokkyomed.ac.jp.
  • Nakajima H; Department of Rheumatology, Dokkyo Medical University, 880 Kitakobayashi, Shimotsuga, Tochigi, Mibu, 321 - 0293, Japan. k-ikeda847@dokkyomed.ac.jp.
Arthritis Res Ther ; 26(1): 55, 2024 02 20.
Article em En | MEDLINE | ID: mdl-38378635
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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença Relacionada a Imunoglobulina G4 Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença Relacionada a Imunoglobulina G4 Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article