2022 Fiscal Year Final Research Report

Immunologic specificity based pathogenesis of IgG4-related diseases and validation in mouse models of the disease

Research Project

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Project/Area Number	20H00553
Research Category	Grant-in-Aid for Scientific Research (A)
Allocation Type	Single-year Grants
Section	一般
Review Section	Medium-sized Section 57:Oral science and related fields
Research Institution	Kyushu University
Principal Investigator	Nakamura Seiji 九州大学, 歯学研究院, 教授 (60189040)
Co-Investigator(Kenkyū-buntansha)	前原隆九州大学, 歯学研究院, 助教 (10637333) 新納宏昭九州大学, 医学研究院, 教授 (20380636) 森山雅文九州大学, 大学病院, 助教 (20452774) 柴田琢磨東京大学, 医科学研究所, 助教 (30554505) 安河内友世 (川久保友世) 九州大学, 歯学研究院, 准教授 (70507813) 坪井洋人筑波大学, 医学医療系, 准教授 (80580505)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	IgG4関連疾患 / T細胞 / B細胞 / マクロファージ / TLR7
Outline of Final Research Achievements	IgG4-related diseases is a unique systemic disease characterized by mass formation and consequent dysfunction of multiple organs, as well as severe fibrosis with infiltrating T cells, B cells, and macrophages. Currently, no effective treatment is available. In this study, we focused on a subset of unique T cells, B cells, and macrophages and performed single-cell RNA sequencing as well as T-B receptor sequencing to obtain a comprehensive, unbiased view of tissue infiltrating cells. As a result, we identified characteristic T and B cell subsets. We also focused on macrophages expressing Toll-like receptor 7 and tested whether it is possible to generate mice that can reproduce the pathology by stimulating them with TLR7 agonist.
Free Research Field	臨床免疫学
Academic Significance and Societal Importance of the Research Achievements	IgG4関連疾患の罹患臓器に浸潤する全T細胞、B細胞、マクロファージを明らかにし、我々が作成したIgG4関連疾患のモデルマウスを用いて特異な細胞群にフォーカスして実際に病態が再現できれば、新たな治療標的薬の開発が可能となる。