Identification of the role of exosomes for inflammation of autoimmune diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09550
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Osaka University
• Principal Investigator: Takamatsu Hyota 大阪大学, 医学系研究科, 助教 (30584411)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 膠原病 / インターフェロン / 核酸 / SLE / 診断 / 核酸受容体 / 内因性膜小胞

Outline of Final Research Achievements

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominates in young women with various organ disorders, and it is pointed out that one of the etiologies is type I interferon (IFN-I) associated with the failure of immune tolerance to its own nuclear components. It has been known that measuring IFN-I in actual SLE patients is difficult due to the low sensitivity of the ELISA method, but we revealed that by using reporter cells, it become possible to evaluate IFN-I activity in serum. Then, we clarified that 1) IFN-I activity and IFN-I-inducing activity is high in SLE serum, 2) there are apoptotic cell-derived membrane vesicles (AdMVs) which contain double-stranded DNA in SLE serum promoted additional production of IFN-I, and that 3) IFN-I production by AdMVs was mediated via the cGAS-STING pathway. These findings are considered to provide the effective and safe medical treatment for SLE.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

SLEに対してインターフェロン受容体を標的とした治療薬開発が進められていますが、すべての患者さんにが有効なわけではありません。レポーター細胞によるモニタリングは、インターフェロン治療が効く症例の層別化に有用で、治療効果のモニタリングにも応用可能であると思われます。また、SLE患者血清における膜小胞を介したインターフェロン産生経路の存在は、今後のより効果的な治療薬の開発に、重要なヒントとなる成果だと思われます。