Examination of regulatory network profiles for gene expression of intestinal epithelial barrier dysfunction in aging

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08581
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Mie University
• Principal Investigator: PARK Eun Jeong 三重大学, 医学系研究科, 准教授 (20644587)
• Co-Investigator(Kenkyū-buntansha): 島岡 要 三重大学, 医学系研究科, 教授 (40281133)
• Research Collaborator: KIYONO Hiroshi ; MIZUGUCHI Kenji
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 老化 / マイクロRNA / 腸管上皮細胞 / エキソソーム / T細胞 / ホーミング / インテグリン

Outline of Final Research Achievements

To elucidate the molecular mechanism of regulating comprehensive gene expressions in intestinal epithelial cells in aging, we analyzed miRNA profiling of epithelial cells in small and large intestines of aged mice. As a result, multiple miRNAs were found to be altered by aging.
To understand the role of T-cell exosomes in tissue specific homing of lymphocytes, we isolated the exosomes from the culture of gut-tropic T cells and analyzed in-vivo homing of lymphocytes. We have found that the exosomes　possess　an　ability　in　negatively　regulating subsequent lymphocyte homing to the gut. This negative effect was considered to be due to expression reduction of the ligand molecules important for lymphocyte homing, possibly by exosomal delivery of miRNAs to the gut endothelial cells.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

生体防御システムである免疫系の老化は、老化による免疫系の機能減退の分子メカニズムの解明は非常に重要な研究課題である。老化に伴う腸管上皮細胞の遺伝子発現調節の分子機序を明らかにすることは重要であり、本研究有意な発現変化を示す多数のマイクロRNAは、今後粘膜免疫関連アンティエイジング研究に結び付ける重要な基礎資料になると考えられる。
腸管移行性T細胞のエキソソームがリンパ球に先回り腸管内皮細胞に、マイクロRNAを伝達し、腸管組織特異的にリンパ球ホーミングを負に制御するという仮説の検証は、新たな炎症性腸疾患治療に向けての基礎研究で創造性が高いと考えられる。