Elucidation of the mechanisms to induce eosinophilic inflammation through ILC2s in allergic rhinitis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16908
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Tojima Ichiro 滋賀医科大学, 医学部, 講師 (80567347)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: アレルギー性鼻炎 / 2型自然リンパ球 / システイニルロイコトリエン / プロスタグランジンD2 / 好酸球 / ラマトロバン / モンテルカスト / ハウスダスト

Outline of Final Research Achievements

Prevalence of ILC2s in the inferior nasal turbinate (INT) tissues and the activating mechanisms of ILC2s were examined in patients with house dust mites (HDM)-induced allergic rhinitis (AR). The prevalence of ILC2s was increased in nasal mucosa of patients with HDM-induced AR, and it was positively correlated with the number of infiltrating eosinophils. ILC2s in the INT tissues expressed a prostaglandin D2 (PGD2) receptor, chemoattractant receptor-homologous molecule expressed TH2 cells (CRTH2), and a cysteinyl leukotrienes (cysLTs) receptor, CysLT1. After nasal provocation test, the number of eosinophils and concentrations of PGD2 and cysLTs were increased in the nasal lavage fluid from AR patients. PGD2 and cysLTs induced IL-5 production from cultured PBMC-derived ILC2s. PGD2-induced and cysLTs-induced production of IL-5 and IL-13 from ILC2s was completely inhibited by ramatroban, a dual CRTH2 and thromboxane receptor antagonist, and montelukast, a CysLT1 antagonist, respectively.

Free Research Field

アレルギー、鼻副鼻腔炎、気道、自然免疫

Academic Significance and Societal Importance of the Research Achievements

アレルギー性鼻炎単独の病態において、鼻粘膜中の2型自然リンパ球がアレルゲン刺激により即時相で産生されたプロスタグランジンD2とシステイニルロイコトリエンに反応してIL-5やIL-13を産生し、好酸球遊走に働く事を初めて明らかにすることで、アレルギー性鼻炎の病態の一端を解明した。これらの刺激はラマトロバン、モンテルカストにより抑制されるため、治療薬の新たな作用機序を明らかにしたことにもつながる。