An investigation of the pathogenic mechanism of IgG4-related disease focusing on the scavenger receptor "MARCO"

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K17265
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kyushu University
• Principal Investigator: ITO Miho 九州大学, 大学病院, 医員 (20778857)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: IgG4 関連疾患 / コラーゲン様構造マクロファージ 受容体 / 自然免疫

Outline of Final Research Achievements

IgG4-related disease (IgG4-RD) is a novel systemic disease entity characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive plasma cells accompanied by severe fibrosis. Although recent studies demonstrated that innate immune cells including monocytes and macrophages might promote local fibrosis and IgG4 production, the pathological mechanism remains unclear.
Macrophage receptor with collagenous structure (MARCO) and Toll-like Receptor (TLR) 7 were identified as disease-associated molecule in IgG4-RD by DNA microarray in submandibular glands from patients with IgG4-RD. Immunohistochemical analysis confirmed that these molecules expression co-localized with CD163+ M2 macrophages. Moreover, M2 macrophages might contribute to the initiation of IgG4-RD via MARCO and TLR7.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

IgG4-RD 発症に MARCO や TLR 7 を介した機序が示唆され、これにより今後、難航しているIgG4-RDモデルマウスの確立、現在の治療の第一選択薬であるステロイドに代わる新しい分子標的治療にも繋がる可能性が多いに期待される。