Identification of a novel receptor for ELC/CCL19 and its role in psoriasis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10217
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kindai University
• Principal Investigator: Nakayama Takashi 近畿大学, 薬学部, 教授 (60319663)
• Co-Investigator(Kenkyū-buntansha): 松尾 一彦 近畿大学, 薬学部, 講師 (70615921)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ケモカイン / ELC/CCL19 / 乾癬

Outline of Final Research Achievements

ELC/CCL19 is a functional ligand for CCR7, which is mainly expressed by naive T and B cells. In the present study, we found that ELC/CCL19 is also a functional ligand for GPCR#13, which is broadly expressed by effector cells such as NK cells and monocytes. We revealed that ELC/CCL19 efficiently induced cell migration in murine L1.2 cells stably expressing GPCR#13 (L1.2-GPCR#13) as well as in L1.2-CCR7. Furthermore, In chemotaxis assays using human PBMCs, ELC/CCL19 attracted not only naive T cells but also CD16(+) NK cells and CD14(+) monocytes. In addition, ELC/CCL19-mediated cell migration was suppressed by treatment with a GPCR#13 antagonist. In mouse psoriasis model, intradermal injection of ELC/CCL19 recruited GPCR#13(+)/CCR7(-) effector cells in psoriasis-like skin lesions and exacerbated psoriasis-like inflammation. These results suggest that ELC/CCL19 another agonist for GPCR#13 and may play an important role in psoriasis by recruiting GPCR#13-expressing effector cells.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

ELC/CCL19の既知受容体であるCCR7は主にナイーブリンパ球に発現していることより、ELC/CCL19は恒常的な免疫応答の誘導に関わると考えられてきた。しかしながら、ELC/CC19がGPCR#13の新たなリガンドであり、GPCR#13を介してエフェクター細胞の炎症巣への遊走を制御しているという知見は、炎症性疾患の病態形成における新たな分子機序の解明に貢献するものであると考えている。さらに、ELC/CCL19が、乾癬を含む炎症性疾患における新たな創薬標的となり得る可能性を示すものである。