Analysis of B cell functions regulating intestinal mucosal permeability on the pathogenesis of Crohn's disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07961
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Shimane University
• Principal Investigator: Ishihara Shunji 島根大学, 学術研究院医学・看護学系, 教授 (80263531)
• Co-Investigator(Kenkyū-buntansha): 三島 義之 島根大学, 学術研究院医学・看護学系, 助教 (30397864) ; 岡 明彦 島根大学, 学術研究院医学・看護学系, 助教 (80600600)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腸管粘膜透過性 / クローン病 / 制御性B細胞 / 制御性T細胞 / IL-10

Outline of Final Research Achievements

In this research project, we hypothesized that abnormalities in regulatory B cells (Breg) are associated with reduced regulation of intestinal mucosal permeability (IMP) and exacerbated intestinal inflammations in Crohn's disease. T and B cells were isolated from the spleen of C57BL/6 mice, administered into the abdominal cavity of Rag2-KO mice, and their IMP was assessed. The IMP was reduced during B cell engraftment compared to T cell engraftment. For the in vitro model of intestinal permeability regulation, a model was created in which the colonic epithelium (Caco-2) were cultured on the apical side of the trans-well, and T or B cells were co-cultured on the basolateral side. In vitro study revealed that the permeability of the epithelium was reduced when co-cultured with B cells rather than T cells, reflecting the results of the in vivo mouse transfer model.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

申請者らはこれまでの研究において「クローン病（CD）における制御性B細胞（Breg）の機能異常を介した炎症増悪メカニズム」を明らかにしていた。さらに今回の申請課題における「腸管の粘膜透過性制御メカニズムを生体の免疫細胞の機能から解明する」という点は、過去に全く報告のない着眼点であった。これらの新規性の高い二つの視点を組み合わせた本研究は、極めて学術的独自性と創造性に富んだ研究内容であることは言うまでもなく、本研究で検証した「Bregによる粘膜透過性制御メカニズム」は、CDのみならず他の“leaky gut”に関わる疾患に対しても、これまでと異なる視点からの病態解明につながると思われる。