Prevention of type 1 diabetes via sensors associated with scavenger receptors such as SR-A

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08917
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Kobe University
• Principal Investigator: Yasuda Hisafumi 神戸大学, 保健学研究科, 教授 (50403233)
• Research Collaborator: SHIMIZU Mami 神戸大学, 大学院医学研究科, 医学研究員 (10757313) ; INOUE Yuto 神戸大学, 大学院保健学研究科 ; WAKAFUJI Ryo 神戸大学, 大学院保健学研究科 ; TAGAMI Kanako 神戸大学, 大学院保健学研究科 ; NISHIKAWA Minaho 神戸大学, 大学院保健学研究科 ; SUZUKI Haruka 神戸大学, 大学院保健学研究科 ; KATSUTA Atsumi 神戸大学, 大学院医学研究科, 研究助手
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: １型糖尿病 / スカべンジャー受容体 / TLR / 病原体感知センサー / 自己免疫

Outline of Final Research Achievements

Recently, it has been reported that the development of type 1 diabetes would be associated with commensal bacteria. So the aim of this study was to examine the association between scavenger receptor A (SR-A) and Toll-like receptor such as TLR4 on dendritic cells and to establish a new immunological preventative and therapeutic strategy for type 1 diabetes. First, lipopolysaccharide (LPS) as a ligand of TLR4 was administered to female NOD mice and cyclophosphamide (CY) -induced diabetes model in male NOD mice. Second, LPS was administered to SR-A KO NOD mice and CY-induced diabetes model in SR-A KO NOD mice. As a result, LPS administration prevented diabetes onset in all four mouse models. Finally, LPS was administered to 8.3 NOD mice transfected with T cell receptor gene of IGRP-specific CD8 T cell clone into NOD mice, resulting in acceleration of T1D onset. Flow cytometric analysis suggested that the Foxp3 regulatory T cells might play a pivotal role in the mechanism of LPS tolerance.

Free Research Field

１型糖尿病