Creation of new allergy treatment by selective removal of allergic memory T cells

• Project/Area Number: 16K19598
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Gifu University
• Principal Investigator: Ikeda Takahide 岐阜大学, 大学院医学系研究科, 助教 (30444326)
• Research Collaborator: Maekawa Youichi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 食物アレルギー / アレルギー

Outline of Final Research Achievements

The relapse of allergic diseases involves an immune memory mechanism mainly composed of antigen-specific memory cells. We examined whether inhibition of Notch signaling could reduce allergy by removing memory cells associated with allergic diseases. BALB / c mice were sensitized with ovalbumin (OVA) and administered with a Notch signal inhibitor (GSI) to induce allergy with OVA oral administration. The Notch signal inhibitor tended to suppress diarrhea and hypothermia, but did not suppress IL-4 production of lymphocytes in the spleen or mesenteric lymph nodes or production of OVA IgE. No suppression of allergic symptoms or suppression of IgE was observed under CD4 antibody administration.

Academic Significance and Societal Importance of the Research Achievements

アレルギー疾患は再燃を起こすが、再燃には抗原特異的メモリー細胞が主体となる免疫記憶機構が密接に関与している。Notchシグナルを阻害することによるアレルギー疾患に関連したメモリーT細胞除去による食物アレルギー再燃抑制ができるかを検討したが、マウスでの食物アレルギー症状の抑制傾向を認めたが、脾臓や腸間膜リンパ節のリンパ球のIL-4産生、血中OVA特異的IgE産生の抑制効果は認めなかった。