Elucidation of regulation mechanism of ocular surface inflammation by IKZF1

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11327
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: UETA MAYUMI 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60398386)
• Research Collaborator: Nishigaki Hiromi ; Ohsako Seiko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: IKZF1

Outline of Final Research Achievements

We found that human epidermis and conjunctival epithelium expressed IKZF1, and in PHCjECs and HEKa, the expression of IKZF1 mRNA was upregulated by stimulation with polyI:C, a TLR3 ligand. In Ikzf1 Tg, we observed dermatitis and mucosal inflammation including the ocular surface. In contact dermatitis model, inflammatory infiltrates in the skin of Ikzf1 Tg were significantly increased compared with wild type. Microarray analysis showed that Lcn2, Adh7, Epgn, Ifi202b, Cdo1, Gpr37, Duoxa1, Tnfrsf4, and Enpp5 genes were significantly upregulated in the epidermis of Ikzf1 Tg compared with wild type.

Free Research Field

眼表面炎症

Academic Significance and Societal Importance of the Research Achievements

全ゲノム関連解析によりIKZF1遺伝子が皮膚粘膜炎症性疾患の発症に大きく関与していることが研究代表者の以前の研究で明らかとなっている。本研究は、生体において、IKZF1遺伝子が皮膚粘膜炎症を制御していることを世界で初めて発見した重要な研究である。本研究により、IKZF1は皮膚粘膜炎症疾患に対する新規治療薬の標的となると考えられる。