Molecular mechanisms of regulation of intestinal immunity by intestinal epithelial cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670142
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kobe University
• Principal Investigator: Matozaki Takasi 神戸大学, 医学(系)研究科(研究院), 教授 (80252782)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 腸上皮細胞 / 炎症 / 生体分子 / 腸内細菌 / シグナル伝達

Outline of Final Research Achievements

SAP-1 is a receptor-type protein tyrosine phosphatase that is localized specifically at microvilli of the brush border in intestinal epithelial cells. I previously found that SAP-1 ablation results in exacerbation of spontaneous colitis in Il10 knockout mice. In this study, I showed that tyrosine phosphorylation of CEACAM, a dephosphorylation substrate for SAP-1, promotes the activation of downstream molecules, thereby inducing production of chemokines such as IL-8. In addition, I found that SAP-1 specifically interacts with CEACAM and that this interaction is mediated via the ectodomains of both proteins. Thus, SAP-1 in intestinal epithelial cells is likely to regulate the intestinal immunity by controlling the tyrosine phosphorylation level of CEACAM.

Free Research Field

生化学