The molecular mechanisms of itch in atopic dermatitis by the peripheral sensory nervous system derived from human iPS cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20686
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0704:Neuroscience, brain sciences, and related fields
• Research Institution: Kyushu University
• Principal Investigator: Yamamura Kazuhiko 九州大学, 大学病院, 助教 (80936427)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: アトピー性皮膚炎 / 痒み / 感覚神経 / iPS細胞

Outline of Final Research Achievements

This study aims to characterize the response of human sensory nerves to pruritogens and explore the mechanism of itch in atopic dermatitis.
MAPK phosphorylation checked in A human neuronal cell line (SH-SY5Y) in the presence of several pruritogenic and pain mediators. However, no significant changes were observed between those mediators. Calcium influx experiments showed specific neuronal excitation induced by pruritogenic mediators. RNA-sequencing in human sensory neurons derived from iPS cells showed specific gene expressions when the cells were cultured with pruritogens. We are currently analyzing the data for submission.

Free Research Field

皮膚科学分野

Academic Significance and Societal Importance of the Research Achievements

本研究によって初めてヒト感覚神経細胞をそう痒惹起物質で刺激した際の反応、神経興奮、遺伝子発現が規定された。このことはアトピー性皮膚炎を含む疾患での痒みのメカニズムを理解する上で非常に重要なことだと考えられる。特に痒みに対してヒト感覚神経は特徴的な神経興奮パターンをとり、特徴的な遺伝子発現があることが明らかとなったため、今後、今回の研究で得られた知見を活かして痒みの神経興奮や特定の遺伝子・タンパクをターゲットとした痒みの治療法が開発される可能性があり、今回の研究は学術的にも社会的にも非常に有意義なものであったと考えられた。