Pathophysiology analysis of IgG4-related disease using single-cell RNA sequence on affected tissue

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08436
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Dokkyo Medical University (2023); Chiba University (2021-2022)
• Principal Investigator: Ikeda Kei 獨協医科大学, 医学部, 教授 (10456014)
• Co-Investigator(Kenkyū-buntansha): 岩田 有史 千葉大学, 大学院医学研究院, 助教 (90436353) ; 中島 裕史 千葉大学, 大学院医学研究院, 教授 (00322024)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: IgG4関連疾患 / 顎下腺 / 単細胞RNAシークエンス / 非血球細胞 / 線維芽細胞 / XV型コラーゲン

Outline of Final Research Achievements

We performed single-cell RNA sequence (scRNAseq) on non-immune cells of submandibular glands from IgG4-related disease (IgG4-RD) and control patients and identified clusters including fibroblasts. The expression of collagen type XV gene (COL15A1) was increased in IgG4-RD and COL15A1-positive fibroblasts showed a distinct gene-expression profile. The serum collagen type XV was elevated in active IgG4-RD patients and decreased after treatment.These results indicate that collagen type XV expressing fibroblasts represent a disease-characterizing non-immune cell population in IgG4-RD and hold potential as a disease-monitoring marker.

Free Research Field

リウマチ性疾患・膠原病

Academic Significance and Societal Importance of the Research Achievements

IgG4関連疾患の病態には不明な点が多く、本研究結果はIgG4関連疾患の免疫細胞から線維化に繋がるメカニズムの一端を解明した。また、IgG4関連疾患はグルココルチコイド依存性の経過を辿ることが多いが、本研究結果は病態に基づいた新規治療標的の同定に繋がる可能性があり、意義の大きな研究結果である。