Dysfunction of mucosal immune education system in chronic inflammation

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03450
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Chiba University
• Principal Investigator: Kurashima Yosuke 千葉大学, 大学院医学研究院, 准教授 (30729372)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 炎症性腸疾患 / 免疫末梢教育 / 線維芽細胞 / 間葉系細胞 / 慢性炎症 / 細胞間相互作用 / 粘膜免疫 / 線維化

Outline of Final Research Achievements

Many types of immune cells are controlled to function appropriately depending on the microenvironment of tissues and organs, mediated by mesenchymal cells, which is known as "tissue specificity". Based on our research, the mechanism of inducing tissue specificity for the immune cells at peripheral site, called the "peripheral immune education system" has been revealed. On the other hand, it has been known that the function of mesenchymal cells is disrupted in chronic inflammation, such as excessive production of extracellular matrix, and it is speculated that disturbance of peripheral immune education system in the microenvironment occurs in this condition.
In this study, we aimed the identification of mesenchymal cells involved in intestinal fibrosis and the mechanisms of alteration of "peripheral immune education system" and it became clear that excessive activation of inflammatory cells is induced by the accumulation of ectopic mesenchymal cells in intestinal tissues.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

間葉系細胞による末梢組織での免疫細胞の成熟機序である「免疫末梢教育機構」を明らかにすることは、組織恒常性の維持機構の理解と疾患発症における分子実態の解明につながる。
本研究から、炎症の遷延化に関わる間葉系細胞群の同定、さらに細胞間相互作用並びに標的分子が見出された。さらに、実験動物モデルでの結果のみならず、ヒト検体を用いた解析からも同様の分子機構が腸炎の重症化に寄与している可能性が示唆されており、本研究課題による成果を基盤として、トランスレーショナルなアプローチによる更なる詳細な解析が期待される。