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KAKEN_15H06589seika.pdf
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腸上皮と上皮間リンパ球の相互作用に基づく粘膜上皮層免疫システムの成立機構の解析
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チョウ ジョウヒ ト ジョウヒカン リンパキュウ ノ ソウゴ サヨウ ニ モトズク ネンマク ジョウヒソウ メンエキ システム ノ セイリツ キコウ ノ カイセキ
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Cho johi to johikan rinpakyu no sogo sayo ni motozuku nenmaku johiso meneki shisutemu no seiritsu kiko no kaiseki
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Study of IEC-IEL interaction in the development of gut epithelial immune system.
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高橋, 大輔
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タカハシ, ダイスケ
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Takahashi, Daisuke
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慶應義塾大学・薬学部・助教
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Research team head
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科研費研究者番号 : 40612130
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Kronenberg, Mitch
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La Jolla Institute for Allergy & Immunology・Division of Developmental Immunology・President & Chief Scientific
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Research team member
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Seo, Goo-young
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La Jolla Institute for Allergy & Immunology・Division of Developmental Immunology・Postdoctoral fellow
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Research team member
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2017
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科学研究費補助金研究成果報告書
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2016
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| Abstract |
上皮細胞に選択的に発現する膜タンパク質輸送因子AP-1Bに着目し, 膜タンパク質輸送を介した腸上皮細胞による上皮細胞間Tリンパ球(IEL)への影響を解析した。タモキシフェン投与により上皮細胞特異的に後天的にAP-1Bを欠損させるマウスを作成し, IELの数と性状を解析したところ, CD8aa陽性のIEL数が1/10程度まで減少していた。また細胞の生存に関わることで知られるBclファミリー分子の発現が増強は増強していた。さらにAP-1Bを欠損マウスから腸上皮細胞のオルガノイドを作成し, 単層培養法を確立した。将来的にIELとの共培養による上皮細胞の性質解析に大きく寄与すると考えられる。
Ap1m2 is predominantly expressed by intestinal epithelial cells (IECs) and functions in the polarized transport of membrane proteins to the basolateral membrane of IECs. We have found the lack of CD8aa expressing intestinal intraepithelial lymphocytes (IELs) in Villin-creERT2 Ap1m2 flox/flox mice when treated with tamoxifen. CD8aa IELs of the IEC specific Ap1m2-deficient mice showed higher levels of Bcl-2 and Bcl-xL expression compared to control littermate mice. These cells also exhibited higher proliferations. These data suggest that protein localization of basolateral membrane on IEC is indispensable for CD8aa IELs numbers and phenotypes. We have established a monolayer culture method with crypts isolated from Villin-creERT2 Ap1m2 flox/flox mice. This monolayer formed tight junctions, and contains both apical and basolateral membrane domains, which is the important characteristic of polarized epithelial cells.
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研究種目 : 研究活動スタート支援
研究期間 : 2015～2016
課題番号 : 15H06589
研究分野 : 粘膜免疫学
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