A novel immunotherapy of autoimmune disease by agonistic toll-like receptor 4 antibody

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460058
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Tohoku University
• Principal Investigator: TSUKAMOTO HIROKI 東北大学, 薬学研究科, 助教 (70423605)
• Co-Investigator(Renkei-kenkyūsha): TOMIOKA Yoshihisa 東北大学, 大学院薬学研究科, 教授 (00282062)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: Toll様受容体 / 自己免疫疾患 / 1型糖尿病 / 免疫寛容 / 機能性抗体 / 抗体医薬 / 自然免疫 / 骨髄由来免疫抑制細胞

Outline of Final Research Achievements

Type 1 diabetes (T1D) is currently an incurable disease as other most autoimmune diseases. The pathology of T1D progresses from a silent prodromal phase to a clinical phase in which insulin-producing pancreatic β cells is destructed by autoreactive T cells. In this study, we demonstrated that an agonistic monoclonal antibody (mAb) to Toll-like receptor 4 (TLR4) prevents from the onset of T1D by prophylactic treatment and also reverses the new-onset of T1D by therapeutic treatment in nonobese diabetic mice. An agonistic TLR4 mAb induces the tolerance in innate immunity via dendritic cells and myeloid-derived suppressor cells, which results in the suppression of autoimmune T cells. In addition, regulatory T cells are also induced by agonistic TLR4 mAb in both periphery and pancreatic islets. These results propose that a tolerance induction through innate immunity by TLR4 mAb may be a novel immunological approach to cure the autoimmune pathology in T1D.

Free Research Field

免疫学