AP-1の転写因子BatfはT(H) 17の微分化を制御する
Barbara U Schraml1, Kai Hildner, Wataru Ise
1Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USA.
Nature
|July 7, 2009
まとめ
転写因子BATFは,宿主防御に不可欠なTヘルパー17 (T(H) (17) 細胞の発達に不可欠であり,自己免疫疾患に関与しています. BATFの喪失はT(H) 17の分化に悪影響を及ぼし,実験的自己免疫性脳内炎から保護します.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- アクティベータータンパク質1 (AP-1) の転写因子は,二分化によって遺伝子発現を調節する.
- AP-1ファミリーのメンバーであるBATFは,正規の活性化ドメインを欠いており,以前はAP-1活動を抑制すると考えられていた.
- Tヘルパー17 (T(H) 17細胞は免疫に不可欠ですが,自己免疫病原性にも関与しています.
研究 の 目的:
- T(H) 17細胞の分化におけるAP-1転写因子BATFの役割を調査する.
- BATFがT(H) 17細胞の発達と機能に影響を与える分子メカニズムを解明する.
主な方法:
- Batf欠乏マウスにおけるT(H) 17細胞の微分化の分析.
- T(H) 1とT(H) 2の細胞の微分化の評価.
- T(H) 17の分化に関連した遺伝子発現の調査 (例えば,RORgamma t,IL21).
- クロマチン免疫降水 (ChIP) は,標的遺伝子プロモーターおよび異種間の要素のBATF結合部位を決定します.
主要な成果:
- Batf (((-/-) マウスは正常なT (((H) 1とT (((H) 2の分化を示しているが,T (((H) 17の細胞分化には重大な欠陥がある.
- Batf (((-/-) T細胞は,T (((H) 17の発達に必要なRORgamma tとIL21のような重要な因子を誘導することができない.
- IL21またはRORgamma tの過剰発現は,Batf (((-/-) T細胞におけるIL17の生成を完全に回復させなかった.
- BATFはIl17,Il21,Il22のプロモーターに直接結合し,Il17a-Il17fロカス内の保存されたインタージェニック要素にも結合する.
結論:
- BATFはT(H) 17細胞の分化に不可欠である.
- BATFは,T(H) 17細胞のアイデンティティと機能の重要なレギュレータとして作用します.
- この発見は,BATFがT(H) 17細胞によって媒介される炎症反応を調節する上で,新しい重要な役割を果たしていることを示しています.
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