Elucidation of Oral Immune Tolerance Mechanisms for Cedar Pollinosis and Search for Novel Drug Target Molecules

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K09912
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Kyushu University
• Principal Investigator: Daisuke Murakami 九州大学, 大学病院, 講師 (80568965)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: スギ花粉症 / 経口免疫療法 / アレルギー性鼻炎

Outline of Final Research Achievements

The mouse model of oral immunotherapy for pollinosis was used to analyze the immune tolerance mechanism and to clarify its safety. Compared to the control group, local and systemic Th2 responses were suppressed in the immunotherapy group (cedar pollen antigen-galactomannan conjugate). On the other hand, enhanced Th1 responses were observed in T cells in mesenteric lymph nodes in the immunotherapy group, indicating differences in T cell immune responses in cervical and intestinal lymph nodes. The number of regulatory T cells in the intestinal lymph nodes did not change between the two groups, suggesting a qualitative difference. No diarrhea or weight loss was observed in the immunotherapy group, confirming its safety, and no cytotoxicity was observed in an in vitro system using Raw264.7 cells.

Free Research Field

アレルギー

Academic Significance and Societal Importance of the Research Achievements

これまで我々は、臨床試験においてスギ花粉症に対するスギ抗原ーガラクトマンナン複合体を用いた経口免疫療法においてその有効性と安全性について明らかにしてきたが生体内での作用機序については不明であった。今回、経口免疫療法花粉症マウスモデルを用いて解析を行い、炎症局所のリンパ節ではTh2反応の抑制がみられ、また一方、腸管ではTh1反応が亢進し、頸部リンパ節と腸管リンパ節でのT細胞免疫応答の違いが認められ、スギ花粉症に対する経口免疫療法の作用機序の一端を明らかにした。またマウスモデルとRaw264.7 cellを用いた実験においてもスギ抗原－ガラクトマンナン複合体の安全性が確認された。