Inhibitory cytokine-producing Treg-mediated control of autoimmunity

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15510
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: The University of Tokyo
• Principal Investigator: Fujio Keishi 東京大学, 医学部附属病院, 教授 (70401114)
• Research Collaborator: KOMAI TOSHIHIKO 東京大学, 医学部附属病院, 特任臨床医 (50803938) ; INOUE MARIKO 東京大学, 医学部附属病院, 特任臨床医 (60816601) ; MORITA KAORU 東京大学, 医学部附属病院, 特任臨床医 ; TERUYA SHUZO 東京大学, 医学部附属病院, 特任臨床医
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 制御性T細胞 / TGF-β / LAG3

Outline of Final Research Achievements

The aim of this project was to elucidate the role of inhibitory cytokine in regulatory T cell (Treg)-mediated control of autoimmunity. Although inhibitory cytokines, such as transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) play major roles in maintaining immune homeostasis, therapeutic application of inhibitory cytokines remains limited due to their pleiotropic and context-dependent effects. In this study, we reveled that a combination of TGF-β and IL-10, but not single cytokine, is required to suppress B cell activation induced by toll-like receptor (TLR) stimulation both in vitro and in vivo. The combination of these two inhibitory cytokines synergistically suppressed cellular energetics of both glycolysis and oxidative phosphorylation in B cells. By exploiting the cytokine synergy-mediated immune suppression, they may provide a new therapeutic method in autoantibody-mediated autoimmune diseases.

Free Research Field

医歯薬学