| Project/Area Number |
18K09314
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | University of Yamanashi (2019-2020)
Chiba University (2018) |
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Principal Investigator |
SAKURAI DAIJU 山梨大学, 大学院総合研究部, 教授 (10375636)
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| Co-Investigator(Kenkyū-buntansha) |
金田 篤志 千葉大学, 大学院医学研究院, 教授 (10313024)
石井 裕貴 山梨大学, 大学院総合研究部, 講師 (40568250)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | アレルギー性鼻炎 / 遺伝子 / エピゲノム / T細胞 / 花粉症 |
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| Outline of Final Research Achievements |
The changes in gene expressions and in epigenetic regulations of lymphocytes in the remission of allergic rhinitis were examined in this study. The peripheral blood lymphocytes before and after the treatment were obtained from the subjects participated in a clinical study of sublingual immunotherapy (SLIT) for the patients with allergic rhinitis. The genes that have changed in their expressions in lymphocytes after SLIT in association with the therapeutic efficacy were explored, and five candidate genes were identified. Next, the gene expressions were validated in the blood lymphocytes obtained from the patients with SLIT in clinical practice, and one gene exhibited the same behavior in the former experiment. This gene encoded an enzymatic molecule linked to compliment. Furthermore, the epigenomic regulations in peripheral T cells by SLIT were examined with ATAC-seq and RNA-seq. As a result, it was suggested that a number of gene regulations were associated with the mechanism of SLIT.
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| Academic Significance and Societal Importance of the Research Achievements |
日本国内においてアレルギー性鼻炎の罹患率の高さと生活の質への影響は大きな問題である。アレルギー性鼻炎の病態形成にはTh2細胞を中心としたリンパ球の免疫応答が重要な役割を持つと考えられるが、アレルゲン免疫療法により誘導される寛解機序におけるリンパ球の役割とその制御機構は十分には解明されていない。本研究において、舌下免疫療法の寛解におけるリンパ球の遺伝子制御およびエピゲノム制御の検討を行い、いくつかの候補遺伝子を同定した。これらは寛解機序に関連する可能性が示唆された。アレルギー性鼻炎の寛解機序の解明は、予防治療や新たな根治治療の開発への発展が期待される。
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