Damage-associated molecular pattern released from intestinal epithelia damaged by bacterial exotoxin induces food allergy
| Project/Area Number |
15K00889
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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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| Research Field |
Eating habits
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 細胞外毒素 / コレラ毒素 / 損傷関連分子パターン （DAMPs） / HMGB1 / 樹状細胞 / 共刺激分子 / 食物アレルギー / 卵白アルブミン / コレラトキシン / 損傷関連分子パターン / 樹状細胞（DC） / DCIR2+ DC / 損傷関連分子パターン（DAMPs） / 細菌外毒素 / 粘膜組織 |
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| Outline of Final Research Achievements |
Cholera toxin (CT) is a mucosal adjuvant and oral administration of ovalbumin (OVA) plus CT induces OVA-specific T cell responses and antibody production in mice.
We showed that oral CT enhances expression of CD80 and CD86 and antigen presentation to T cells of intestinal dendritic cells (DCs). We found that oral CT enhances cell death and cytoplasmic expression of high-mobility group box 1 protein (HMGB1) in intestinal epithelial cells (IECs), and fecal HMGB1 levels. HMGB1 dose-dependently enhanced the expression of CD80 and CD86 on DCs in vitro, and intravenous or oral administration of glycyrrhizin, an HMGB1 inhibitor, suppressed intestinal DC activation and induction of OVA specific T cell responses, IgA production, and delayed-type hypersensitivity induced by oral CT.
These results showed that oral CT triggers cell death of IECs and the release of HMGB1 from the damaged IECs, and that the released HMGB1 may mediate antigen sensitization and progression of food allergy.
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| Academic Significance and Societal Importance of the Research Achievements |
粘膜や皮膚は様々なアレルゲンが体内に入る門戸であると同時に、細菌感染などにより細胞損傷を受けやすい部位でもある。細菌外毒素により損傷した腸管上皮は損傷関連分子パターンであるHMGB1を放出し、アレルギー・炎症を引き起こす起点となることが明らかとなった。損傷上皮から侵入したアレルゲンは活性化樹状細胞に取り込まれ、T・B細胞活性化と抗体産生を誘導し、食物アレルギーを引き起こす可能性が示唆された。
食物アレルギーの予防のために、消化器急性感染時は粘膜損傷が治癒するまでアレルゲンを含む食品の摂取を控えた方がよいと考えられる。アレルギー予防の食事指針の確立に向けて、本研究結果は極めて重要な意義を持つ。
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Report
(5 results)
Research Products
(24 results)
