Single-cell RNA sequencing of submandibular gland reveals collagen type XV-positive fibroblasts as a disease-characterizing cell population of IgG4-related disease
© 2024. The Author(s)..
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.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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Enthalten in: |
Arthritis research & therapy - 26(2024), 1 vom: 20. Feb., Seite 55 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Tanaka, Shigeru [VerfasserIn] |
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Links: |
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Themen: |
9007-34-5 |
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Anmerkungen: |
Date Completed 22.02.2024 Date Revised 26.02.2024 published: Electronic Citation Status MEDLINE |
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doi: |
10.1186/s13075-024-03289-7 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM368686582 |
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245 | 1 | 0 | |a Single-cell RNA sequencing of submandibular gland reveals collagen type XV-positive fibroblasts as a disease-characterizing cell population of IgG4-related disease |
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520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Collagen type XV | |
650 | 4 | |a Fibroblasts | |
650 | 4 | |a IgG4-related disease | |
650 | 4 | |a Single-cell RNA sequence | |
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700 | 1 | |a Yamamoto, Takuya |e verfasserin |4 aut | |
700 | 1 | |a Iwata, Arifumi |e verfasserin |4 aut | |
700 | 1 | |a Kiuchi, Masahiro |e verfasserin |4 aut | |
700 | 1 | |a Kokubo, Kota |e verfasserin |4 aut | |
700 | 1 | |a Iinuma, Tomohisa |e verfasserin |4 aut | |
700 | 1 | |a Sugiyama, Takahiro |e verfasserin |4 aut | |
700 | 1 | |a Hanazawa, Toyoyuki |e verfasserin |4 aut | |
700 | 1 | |a Hirahara, Kiyoshi |e verfasserin |4 aut | |
700 | 1 | |a Ikeda, Kei |e verfasserin |4 aut | |
700 | 1 | |a Nakajima, Hiroshi |e verfasserin |4 aut | |
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