Establishing a platform for molecular analysis and drug innovation of auto-inflammatory disorders

2016 Fiscal Year Final Research Report

• Project/Area Number: 26253062
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyoto University
• Principal Investigator: Heike Toshio 京都大学, 医学研究科, 教授 (90190173)
• Co-Investigator(Kenkyū-buntansha): 八角 高裕 京都大学, 医学(系)研究科(研究院), 講師 (00511891) ; 小原 收 公益財団法人かずさDNA研究所, その他部局等, その他 (20370926) ; 河合 朋樹 京都大学, 医学(系)研究科(研究院), 助教 (20631568) ; 西小森 隆太 京都大学, 医学(系)研究科(研究院), 准教授 (70359800) ; 斎藤 潤 京都大学, 学内共同利用施設等, 准教授 (90535486)
• Research Collaborator: IZAWA Kazushi 京都大学, 大学院医学研究科発達小児科学, 助教 (90634931)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 自己炎症性疾患 / インフラマソーム / iPS細胞 / 病態解明

Outline of Final Research Achievements

We identified high-frequency somatic NLRC4 mosaicism as a cause of CAPS phenotype in a patient who lacks NLRP3 mutation through phenotype dissection using patient-derived iPS cells. For the analysis of pathophysiology of chondrohyperplasia in CAPS, we stablished isogenic iPSCs with wild-type and mutant NLRP3 derived from CAPS patients carrying NLRP3 somatic mosaicism, and found that mutant iPSCs produced larger chondrocyte masses through increased expression of the chondrocyte master regulator SOX9. We also investigated the pathophysiology of AGS (Aicardi-Goutieres Syndrome) by using IFIH1 mutant mice. These mice showed increased transcript levels of type I interferon response genes in various organs and encephalitis-like brain lesions, indicating that these mice are useful as an AGS disease model.

Free Research Field

小児免疫疾患