Regulation of TGF-b-dependent class switching by intestinal dendritic cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07614
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Fujita Health University
• Principal Investigator: Tezuka Hiroyuki 藤田医科大学, 研究推進本部 オープンファシリティーセンター, 講師 (30375258)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 樹状細胞 / TGF-β / クラススイッチ / 腸管関連リンパ組織 / 腸内細菌

Outline of Final Research Achievements

TGF-beta, an abundant cytokine in the intestinal mucosa, is essential for isotype class-switching (CSR) into IgA and IgG2b in B cells. We found that IgA and IgG2b CSR are predominantly induced in the Peyer's patches and cecum patches, respectively. Consistent with this result, dendritic cell (DC) subsets that induce IgA-producing B cells were predominantly found in the Peyer's patches, where factor(s) X that induce the DC subsets were constitutively produced at high levels under steady-state conditions. Therefore, these findings suggest that the generation of DCs that differentially regulate TGF-b-dependent CSR in the intestine is dependent on their microenvironment.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、腸管関連リンパ組織(GALT)の部位特異的な微小環境がB細胞の運命を決定する上で重要な役割があること、さらに同環境の構築は同所に存在する樹状細胞の機能に依存している可能性を示した。病原体の感染に対して、粘膜面では抗原特異的IgA、血中では特異的IgGを誘導する「粘膜ワクチン」が待望されている。本成果は、樹状細胞の人為的制御に基づく粘膜ワクチンの開発に資する可能性を秘めている。