Clarifying the molecular mechanism of autoinflammation caused by dysfunction of immunoproteasome complexes

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461595
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: The University of Tokushima
• Principal Investigator: KITAMURA Akiko 徳島大学, 大学院医歯薬学研究部, 助教 (10448318)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 自己炎症症候群

Outline of Final Research Achievements

We found two Japanese families suffered from an autoinflammatory syndrome characterized by recurrent fever, nodular erythema and partial lipodystrophy (JASL) and identified a missense mutation in the immunoproteasome subunit PSMB8. The PSMB8 mutation caused autoinflammation through the dysfunction of immunoproteasome complexes, but the underlying molecular mechanism has not been clarified. To understand how dysfunction of immunoproteasomes causes autoinflammation, we established knock-in mouse harboring the same Psmb8 mutation as JASL patients and transgenic mice that expressed mutant Psmb8 under the invariant chain promoter. Both genetically modified young mice did not show any signs of inflammation and splenomegaly. The Psmb8 knock-in mice had a defect in adipocytes differentiation, which would be attributable to lipodystrophy phenotypes in JASL patients.

Free Research Field

医歯薬学