Elucidation of mechanisms of peripheral itch hypersensitivity focusing on dorsal root ganglia and development for its therapeutic application

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08997
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Juntendo University
• Principal Investigator: TAKAMORI KENJI 順天堂大学, 医学部, 特任教授 (40053144)
• Co-Investigator(Kenkyū-buntansha): 冨永 光俊 順天堂大学, 医学(系)研究科(研究院), 先任准教授 (50468592) ; 鎌田 弥生 順天堂大学, 医学(系)研究科(研究院), 助教 (00410035) ; 梅原 芳恵 順天堂大学, 医学(系)研究科(研究院), 博士研究員 (40707072)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: かゆみ過敏 / サテライトグリア / アトピー性皮膚炎 / 感覚神経 / リポカリン２

Outline of Final Research Achievements

This study was performed to reveal the roles of satellite glial cells (SGC) derived lipocalin-2 (LCN2) in the pathogenesis of atopic dermatitis (AD) using an AD model NC/Nga mouse. AD-like symptoms were induced by application of Dermatophagoides farinae body (Dfb) twice a week for 3 weeks. LCN2 mRNA and protein expressions in dorsal root ganglion (DRG) were higher in AD-NC/Nga- than control NC/Nga-mice. Immunohistochemically, LCN2 was co-localized with GLAST, a marker of SGC, in DRG. The number of LCN2-immunoreactive SGC was increased in the DRG of AD-NC/Nga mice. Expression level of LCN2 mRNA was increased faster in the DRG than the spinal cord during induction of dermatitis in NC/Nga mice. Intrathecally administrated anti-LCN2 antibody twice a week for 3 weeks reduced dermatitis score in AD-NC/Nga mice, but did not affect scratching behavior. Thus, SGC derived lipocalin-2 may be involved in the pathogenesis of dermatitis in AD-NC/Nga mice.

Free Research Field

皮膚科学、生化学、かゆみ科学

Academic Significance and Societal Importance of the Research Achievements

近年、世界的にアトピー性皮膚炎(AD)の有病率は上昇しており、本研究領域への国民の関心も非常に高い。このような背景において、後根神経節(DRG）とsatellite glial cell（SGC）の相互作用に着眼した本研究成果は体性感覚分野の発展に役立つとともに、将来、『難治性かゆみの克服』と『QOL向上』に向けたADの新規治療法の開発に結び付くことが期待される。