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KAKEN_25670234seika.pdf
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Download
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:459.5 KB
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:Apr 11, 2016 |
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Total downloads since Apr 11, 2016 : 540
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T細胞分化制御のシステムバイオロジー
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Tサイボウ ブンカ セイギョ ノ システム バイオロジー
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Tsaibo bunka seigyo no shisutemu baioroji
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Systemic biology of T cell differentiation
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吉村, 昭彦
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ヨシムラ, アキヒコ
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Yoshimura, Akihiko
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慶應義塾大学・医学部・教授
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Research team head
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科研費研究者番号 : 90182815
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山田, 訓
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ヤマダ, サトシ
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Yamada, Satoshi
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岡山理科大学・工学部・教授
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Research team member
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科研費研究者番号 : 20393506
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2015
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科学研究費補助金研究成果報告書
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2014
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ヘルパーT細胞は免疫制御の中心を担う細胞である。近年, Th1, Th2以外に多くのサブタイプ(Th9, Th17, iTreg等)が存在していることが知られるようになってきた。本研究ではTGFβのシグナル伝達経路を中心にヘルパーT細胞各サブタイプへの分化制御機構の解明を行った。まずTGFβとIL-4によるTh9分化にはSmad2/3に依存し, さらにIRF4との共同作用が必要であることを明らかにした。さらに消化管におけるiTregの誘導には樹状細胞からのTGFβが重要であること, TGFβの産生には腸内細菌によるTLR2-AP1経路とSmad3経路が重要であることを見いだした。
Helper T cells have been thought to play a central role in not only acquired immune responses but also in immune regulation. Recently, several subsets such as Th9, Th17 and iTreg have been discovered in addition to Th1 and Th2. Differentiation of each helper T cell subset is extremely complicated. Thus, we have tried to define the mechanism of helper T cell differentiation by focusing on TGF-beta signaling. We discovered Th9 differentiation by TGF-beta and IL-4 is Smad2/3 dependent and required for IRF4 transcription factor. We also found that TGF-beta from dendritic cells plays important role in iTreg differentiation in the gut. We showed that the TLR2-AP-1 pathway as well as the Smad3 pathway are critical for TGF-beta production by intestinal microflora.
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研究種目 : 挑戦的萌芽研究
研究期間 : 2013～2014
課題番号 : 25670234
研究分野 : 分子免疫学
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