転写因子アケエテ-エキュートホモログ2は,卵泡のTヘルパー細胞の発達を開始する
Xindong Liu1, Xin Chen2, Bo Zhong3
11] Tsinghua University School of Medicine, Beijing 100084, China [2] Department of Immunology, MD Anderson Cancer Center, Houston, Texas 77054, USA.
Nature
|January 28, 2014
まとめ
アキエテ・スキュート・ホモログ2 (Ascl2) は,CXCR5を上調し,CCR7を下調することによって,毛細葉のTヘルパー (TFH) 細胞の発達を直接開始する. この転写因子は,TFH細胞の分化と生殖中心の反応に不可欠です.
科学分野:
- 免疫学 免疫学とは
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
背景:
- フォリキュラーTヘルパー (TFH) 細胞は,B細胞のヘルパーと生殖中心の形成に不可欠な,特化したCD4 (((+)) T細胞サブセットです.
- Bcl6はTFH機能に不可欠であるが,CXCR5のアップレギュレーションによって特徴づけられる初期TFHプログラム誘導とT細胞移行におけるその役割は不明である.
研究 の 目的:
- TFH細胞の発達と機能におけるアケエト・スキュートホモログ2 (Ascl2) の役割を調査する.
- Ascl2がCXCR5やCCR7のような重要なTFH細胞マーカーを調節し,T細胞の移転と分化に及ぼす影響を決定する.
主な方法:
- CXCR5とCCR7の調節を評価するために,T細胞におけるAscl2の子宮外発現のインビトロ研究.
- T細胞の移動とTFH細胞の発達に対するAscl2の効果を評価するインビボマウスモデル.
- Ascl2の標的遺伝子を特定するための全ゲノム分析.
- CD4 ((+)) T細胞におけるAscl2の急性欠損とId3タンパク質のブロック.
- TFH細胞生成に対するId3変異の影響の分析.
主要な成果:
- Ascl2は,TFH細胞で選択的に上位調節され,子宮の外表はCXCR5を上位調節し,CCR7を下位調節する.
- Ascl2は,T細胞の卵泡への移住を加速し,TFH細胞の発達をin vivoで促進する.
- 全ゲノム分析により,Ascl2はTFH関連の遺伝子を直接調節し,Tヘルパー1 (TH1) とTヘルパー17 (TH17) のシグネチャー遺伝子を抑制することが明らかになった.
- 急性Ascl2欠失またはId3阻害は,TFH細胞の発達と生殖中心の応答を損なう.
- Id3変異はTFH細胞生成を高め,Id3の抑制作用を示唆しています.
結論:
- Ascl2は,重要なケモカイン受容体とTFH特異的な遺伝子発現を調節することによって,TFH細胞の発達を直接開始します.
- Ascl2は,T細胞がB細胞の卵泡に移行し,生殖中心の反応を誘導する上で重要な役割を果たします.
- Ascl2とId3のバランスは,TFH細胞の分化を制御し,自己免疫を予防するために重要です.
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