Improvement of sublingual immunotherapy by activating invariant NKT cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16891
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Chiba Cancer Center (Research Institute) (2018); Chiba University (2017)
• Principal Investigator: Sakurai Toshioki 千葉県がんセンター(研究所), 頭頸科, 医長 (10791999)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: アレルギー性鼻炎 / 舌下免疫療法

Outline of Final Research Achievements

Sublingual immunotherapy (SLIT) requires a long administration period to establish stable and adequate responses. This study investigated the efficacy of the sublingual administration of an allergen with liposomes enclosing α-Galactosylceramide (α-GC-liposome) as a potential adjuvant in mice with AR. Mice with AR induced by OVA received the sublingual administration of OVA, α-GC-liposomes, or OVA plus α-GC-liposomes for 7 days. After nasal re-challenge with OVA, the combined sublingual administration of α-GC-liposomes and OVA completely suppressed nasal symptoms, downregulated Th2 type cytokine production in CD4-positive T cells, and upregulated Th1 type cytokine production in CLN cells. Additionally, the serum levels of specific IgG2a were promoted, and specific IgE and IgG1 were inhibited. Our findings suggest that the sublingual administration of an allergen with α-GC-liposomes as an adjuvant might increase the therapeutic efficacy and effectiveness of this treatment method.

Free Research Field

アレルギー

Academic Significance and Societal Importance of the Research Achievements

アレルギー性鼻炎に対する根本療法として舌下免疫療法が普及しつつあるが、治療に数年を要し、効果予測が難しいなど課題が残されている。今回、抗原投与と同時にアレルギー性鼻炎モデルマウスのInvariant NKT（iNKT）細胞の賦活化を行ったところ、鼻炎症状（くしゃみ回数、鼻かき回数）や血清抗原特異的IgE値は未発症群と同程度まで抑制された。iNKT細胞免疫系の賦活化は、抗原舌下投与による鼻炎症状抑制効果の発現を促進していると考えられた。