Elucidation of epigenetic mechanism required for chronic inflammatory phenotype in conjunctival fibroblasts derived from severe allergic conjunctivitis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11500
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Nihon Pharmaceutical University (2018-2019); National Center for Child Health and Development (2017)
• Principal Investigator: OKADA NAOKO 日本薬科大学, 薬学部, 助教 (50636165)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: エピジェネティクス / ペリオスチン / 重症アレルギー性結膜炎 / 線維芽細胞

Outline of Final Research Achievements

Atopic keratoconjunctivitis (AKC) represents severe forms of ocular allergies. It is characterized by chronically relapsing ocular inflammatory diseases that cause intense inflammation and fibrosis in conjunctiva. However, the precise mechanisms by which the diseases are resistant to treatment remains unknown. We previously focused on conjunctival fibroblasts derived from severe ocular allergic conjunctivitis patients and compared the gene expression patterns. It was found that the expression of periostin was significantly enhanced in the conjunctival fibroblasts derived from patients in the unstimulated state, and this expression was maintained even after the subculture. In this study, we found that epigenetic induction by enzymes involved in histone methylation status play an important role in periostin high expression in conjunctival fibroblasts. Furthermore, it was revealed that high expression of periostin in conjunctival fibroblasts can be suppressed by controlling the enzymes.

Free Research Field

眼アレルギー

Academic Significance and Societal Importance of the Research Achievements

線維芽細胞はがんや関節リウマチなど様々な慢性炎症疾患において、炎症局所の微小環境中での様々なストレスに応答し、細胞のエピジェネティック変化が誘導されることで、慢性炎症を引き起こすことが数多く報告されている。一方、アレルギー疾患においては、炎症組織中の細胞を採取・評価できる疾患が少なく、検討が進んでいない。本研究では結膜線維芽細胞を用いて、慢性炎症型の表現型獲得とその維持のために重要なエピジェネティクスのメカニズムとその制御法を初めて解明した。またエピジェネティクス制御化合物は、眼アレルギーに限らず、炎症メカニズムが類似した疾患における治癒困難な線維化に対し、新たな治療法となる可能性がある。