Analysis for the immunological and physiological pathogenesis of prurigo

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08805
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: National Defense Medical College
• Principal Investigator: SATOH TAKAHIRO 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 皮膚科学, 教授 (30235361)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 痒疹 / 好塩基球 / IL-31 / ERK2 / アロネーシス

Outline of Final Research Achievements

Prurigo is a treatment-resistant disease. We analyzed immunological mechanisms and itch transmission systems in prurigo. In mouse prurigo model, amphiregulin derived from basophils played essential roles in the development of prurigo reaction. Prurigo-like skin lesions in scabies patients, significant levels of IL-31 were expressed. Notably, IL-31 was principally generated by M2 macrophages, but not T cells. With experiments with nervous system ERK2 conditional knockout mice, we found that central nervous ERK2, but not peripheral nervous ERK2, was essential for mechanical itch during chronic contact hypersensitivity and prurigo reactions. In a treatment-resistant prurigo patient, duloxetine hydrochloride exhibited therapeutic effects. Similarly, mirogabalin was effective for prurigo associated with neuropathic itch. In this research project, we also published a revised version of the guideline for the diagnosis and treatment of prurigo.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

痒疹の発症機序の一部、そしてかゆみサイトカインであるIL-31の産生細胞、さらに痒みを伝達する中枢神経でのシグナルにおけるERK2の役割などが明らかになり、痒みや痒み過敏に対する今後の治療標的を定めるうえで有用な知見がえられた。また新たな痒疹の分類と改訂診療ガイドラインの作成、さらに限られた症例ながら有望な薬剤も提示され、治療効果を享受できる患者が今後みられるようになると期待している。