Analysis of control mechanism of inflammasome and application to treatment of autoimmune diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09923
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyushu University
• Principal Investigator: HIROKI MITOMA 九州大学, 大学病院, 助教 (60467909)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 自己免疫疾患 / マクロファージ / インフラマソーム

Outline of Final Research Achievements

Human CD16-positive monocytes had high ability to secrete active form of IL-1β. Secretion of active IL-1β from peripheral blood monocytes after LPS stimulation was higher in rheumatoid arthritis (RA) with high disease activity compared to healthy controls, because CD16 positive monocytes were increased in active RA. The suppressive reagents for IL-1 β secretion was examined. Colchicine inhibited IL-1β secretion from LPS-stimulated monocytes at high concentrations. Hydroxychloroquine also suppressed IL-1β secretion from LPS stimulated monocytes. There was no extracellular release of the cytoplasmic components of monocytes and no cell death was observed. Therefore, it was considered that the secretion of active IL-1β from monocytes was mediated by a different pathway from pyroptosis in macrophages.

Free Research Field

臨床免疫学

Academic Significance and Societal Importance of the Research Achievements

ヒトの自己免疫疾患におけるインフラマソームの病態形成への役割は明らかとなっていない。今回我々は関節リウマチの単球において、インフラマソーム経路が活性化していることを明らかにした。また現在全身性エリテマトーデスの治療薬として使用されているヒドロキシクロロキン（HCQ）はインフラマソームの活性化を抑制することを見出した。インフラマソームの関与が想定される病態、疾患においてHCQが有用である可能性が示唆された。