Analysis and therapeutic application of intestinal epithelial cell plasticity in inflammatory bowel disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05284
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Okamoto Ryuichi 東京医科歯科大学, 統合研究機構, 教授 (50451935)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 炎症性腸疾患 / 腸上皮幹細胞 / 分泌型上皮細胞 / 可塑性

Outline of Final Research Achievements

Through our current research project focused on mucosal damage in inflammatory bowel diseases, we found and confirmed a novel endogenous tissue repair system supported by a secretory-type cell population (Atoh1-positive cells) distinct from the genuine intestinal stem cells. In addition, we successfully identified a novel genetic marker, UBD, for the prediction of favorable clinical outcome in response to anti-TNF-a therapy. Expression of UBD was regulated by a synergistic enhancement between the TNF-a pathway and the Notch signaling pathway, as confirmed by experiments using patient-derived intestinal epithelial cells.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

炎症性腸疾患において幹細胞とは異なる上皮細胞分画による新たな組織修復機構の存在を明らかにしたことにより、同細胞の機能を活用した新たな粘膜再生・修復治療に繋がる成果を提示した。同疾患における抗TNF-a抗体治療の効果予測指標となり得る遺伝子UBDの同定については、当該治療を実施した患者における治療の有効性を早期に予測し、より適切な治療の選択が可能となることに貢献することが期待できる。