| Project/Area Number |
18K05502
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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 38050:Food sciences-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
八村 敏志 東京大学, 大学院農学生命科学研究科(農学部), 准教授 (40238019)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 消化管アレルギー / 食物アレルギー性小腸炎 / IL-4 / 骨量減少 / 破骨細胞 / CD69 / 腸炎惹起性記憶T細胞 / 腸管膜リンパ節 / 活性化T細胞 / 記憶T細胞 / OVA23-3マウス / 卵白アルブミン / food allergy / intestinal inflammation / ovalbmin / bone loss / osteoclast |
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| Outline of Final Research Achievements |
This study was conducted to clarify roles of pathogenic-memory T cells via the cell-surface molecule of CD69 in inducing bone loss in a food allergic enteropathy model. However, changes of phenotype of the model interrupted the progress. We succeeded to indicate roles of IL-4 and IL-4-producing pathogenic-memory T cells in the bone loss induction: 1) IL-4 played an important role in primary phase, but in its chronic phase, unknown factors than IL-4 contributed more significantly. 2) Pathogenic-memory T cells which in-flowed from mesenteric lymph nodes (MLNs)to bone marrow (BM) was suggested to play a role as a trigger to create IL-4-dominance milieu in the bone, but in BM, the T cells were not major producers of IL-4. In MLNs, different from BM, the T cells were major producers of IL-4. 3) IL-4 inhibited osteoclast differentiation, but rIL-1beta added to rIL-4-dominant in vitro culture system, canceled the inhibitory effect of rIL-4 and induced TRAP-positive cells from preosteoclasts.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、食物アレルギー性小腸炎モデルマウスにおいて全身性の各リンパ組織で産生されるIL-4と腸炎惹起性IL-4産生記憶T細胞が消化管アレルギーの腸と骨で異なる機構で炎症形成に作用することを示した。すなわち、卵白食の長期投与により誘導される脱感作状態は、腸炎を軽減するが、臨床的に認識しにくい骨量減少は抑制しないことを示唆した。よって今後の骨量減少を伴う可能性のある消化管アレルギーの治療において、腸管免疫系を経由した寛容誘導における免疫応答の評価を遠隔組織である骨で同様の抑制状態を反映するか見直す必要性を示した点で学術的・社会的意義がある成果である。
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