Novel therapy targeting autophagy/LAP balance in SLE skin eruption

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16265
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kyushu University
• Principal Investigator: Fuyuno Yoko 九州大学, 医学研究院, 助教 (30529855)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: SLE / AHR

Outline of Final Research Achievements

The activation kinetics of the AHR, NRF2, and EGFR pathways were examined in NHEK when autophagy was induced, inhibited, or LAP inhibited. It was determined that CYP1A1 tended to increase regardless of autophagy/LAP, which may be due to reagent characteristics, and that autophagy/LAP balance and activation of the AHR could not be evaluated with autophagy inducers/inhibitors or LAP inhibitors. Stimulation of keratinocytes with synthetic nucleic acid and IFNα resulted in the appearance of SLE skin rash-like signals. Further treatment with AHR ligand showed suppression of some of the above SLE-like skin rash signals.

Free Research Field

Dermatology

Academic Significance and Societal Importance of the Research Achievements

全身性エリテマトーデス（SLE）の治療は、これまでステロイド内服などの免疫抑制剤が治療の主体であったが、近年ステロイドを減薬させることができるような、長期的に安全な新規治療薬の開発が望まれている。炎症性皮膚疾患の新たな治療ターゲットとして、AHR（Aryl hydrocarbon receptor; 芳香族炭化水素受容体）が注目されている。本研究で初めてSLE皮疹に対するAHRの活性化の効果の可能性について検討を行い、SLE皮疹に対する新たな治療の可能性を示した。