The Role of Innate Immunity in IgG4-Related Diseases and the Search for Novel Therapeutic Targets

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K09999
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kanazawa Medical University (2019-2022); Kanazawa University (2017-2018)
• Principal Investigator: YAMADA Kazunori 金沢医科大学, 医学部, 准教授 (90397224)
• Co-Investigator(Kenkyū-buntansha): 塚 正彦 金沢大学, 医学系, 教授 (00272956) ; 伊藤 清亮 金沢大学, 附属病院, 医員 (10467110) ; 川野 充弘 金沢大学, 附属病院, 講師 (20361983) ; 水島 伊知郎 金沢大学, 附属病院, 助教 (50645124) ; 原 怜史 金沢大学, 医学系, 助教 (80749820)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: IgG4関連疾患 / 自然免疫 / Toll-like receptor-9 / Galectin-3

Outline of Final Research Achievements

In salivary gland tissues from patients with IgG4-related diseases, galectin-3, produced by M2 macrophages, is expressed at inflammation sites. It was confirmed that TLR-9 expression coincided with sites of inflammation in the kidneys of LAT Y136F knock-in mice. Thereafter, CpG oligodeoxynucleotides (CpG-ODN), a TLR-9 agonist, were administered to the mice to determine if the lesions could be alleviated by shifting the immune response to a Th1 response. The results demonstrated that administration of CpG-ODN from the age of 6 weeks suppressed the progression of lung lesions. However, when CpG-ODN was administered from the age of 9 weeks, the formation of granulomas was observed.

Free Research Field

リウマチ・膠原病内科

Academic Significance and Societal Importance of the Research Achievements

IgG4関連疾患における自然免疫の関与については、これまでも報告されているが、今回Gal-3やTLR-9もIgG4関連疾患の病態形成に何らの影響を与えている可能性が示唆された。今後、新規薬剤のターゲットの候補分子としての基礎となるデータを得た点が学術的意義があると考える。