Mechanism and functional analysis of abnormal activation of antigen presenting cells in inflammatory bowel disease

• Project/Area Number: 17K16546
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: Sekido Yuki 大阪大学, 医学部附属病院, 医員 (00781709)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Crohn's Disease / CD163 / myeloid cell / RNA sequencing / CD14 / Crohn's disesase / myeloide cell / Crohn’s Disease / IBD / innate myeloid cell / human colon / RNA-seq analysis / 炎症性腸疾患 / クローン病 / 抗原提示細胞 / Th17

Outline of Final Research Achievements

BACKGROUND: Human intestinal myeloid cells are involved in intestinal homeostasis,however in inflammatory bowel diseases such as Crohn's disease, each subset exhibits abnormal activation. In this study, we analyzed gene expression pattern of Crohn's disease patients.
METHODS: The intestinal samples were collected from 3 cases of Crohn's disease and 4 cases of colon cancer, and 3 fractions of CD14+CD163low, CD14-CD11c+, CD14-CD11c- were collected using flow cytometry. RNA sequencing and GeneOntology analysis were performed.
RESULTS: The expression pattern among three subsets in normal intestine was different. The former two subsets had different expression patterns in normal and Crohn's disease cases.

Academic Significance and Societal Importance of the Research Achievements

少数サンプルでの研究ではあるが、ヒト腸管ミエロイド細胞のサブセット特有の発現変動パターンを明らかにした。また、各サブセットにおいて正常腸管に対してクローン病において特有の発現変動パターンを明らかにした。それぞれの発現変動のGO解析ではそれぞれの発現変動に特有にenrichされるGOを明らかにした。
今後今回同定されたサブセット固有にenrichされていた病態への関与が疑われるPathwayなどの機能解析を行うことで炎症性腸疾患症例の腸管ミエロイド細胞におけるサブセット特異的な異常活性化のメカニズムが明らかになれば病態解明に繋がる可能性があり、病態に基づいた治療開発に繋がる可能性がある。

Research Products

• [Journal Article] Innate Myeloid Cell Subset-Specific Gene Expression Patterns in the Human Colon are Altered in Crohn's Disease Patients. (2018)
  • Author(s): Sekido Y, Yasumizu Y, Nishimura J, Kayama H, Matsuno H, Ogino T, Miyoshi N, Takahashi H, Haraguchi N, Hata T, Matsuda C, Doki Y, Mori M, Takeda K, Ohkura N, Sakaguchi S, Mizushima T.
  • Journal Title: Digestion Volume: 19: Issue: 3 Pages: 1-11
  • DOI: 10.1159/000490890
  • Peer Reviewed / Open Access
• [Presentation] Innate Myeloid Cell Subset-Specific Gene Expression Patterns in the Human Colon are altered in Crohn’s Disease Patients (2018)
  • Author(s): Junichi nishimura, Tsunekazu Mizushima, Masaki Mori
  • Organizer: JDDW International Session 1 消化器病学会・消化器内視鏡学会