転写因子GATA-3は,CD4T細胞におけるTh2サイトカイン遺伝子発現に必要かつ十分である

W Zheng¹, R A Flavell

¹Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.

Cell

|May 16, 1997

まとめ

GATA-3は,ユーモラル免疫に不可欠なTh2細胞の発達を促す重要な転写因子です. この研究は,GATA-3がTh2サイトカイン遺伝子発現に不可欠で十分であることを示しています.

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:

CD4 T細胞は,T1およびT2サブセットに分離し,異なる免疫応答を媒介する.
Th1/Th2細胞の分化を制御する分子機構は,まだ完全に理解されていません.

研究の目的:

CD4 Tヘルパー細胞の分化におけるGATA-3の役割を明らかにする.
GATA-3がTh2細胞発育とサイトカイン発現に必要で十分かどうかを判断する.

主な方法:

ネイブ,Th1,Th2のT細胞集団におけるGATA-3発現の分析.
Th2 サイトカインの遺伝子発現を抑制するために,アンチセンセス GATA-3 の使用.
レポーター遺伝子解析は,IL-4プロモーターに対するGATA-3の効果を評価するためのものです.
CD4 T細胞でGATA-3発現が上昇したトランスジェニックマウスの生成.

主要な成果:

GATA-3の発現は,Th2細胞とナイブT細胞では選択的に高く,Th1細胞では減少しています.
AntisenseのGATA-3治療は,Th2サイトカインの遺伝子発現を阻害しました.
GATA-3は直接IL-4プロモーターを活性化させました.
発達中のTh1細胞におけるGATA-3の過剰発現は,Th2サイトカインの遺伝子発現を誘発した.

結論:

GATA-3は,Th2細胞の微分化の重要な調節体である.
GATA-3は,Th2固有のサイトカインの発現に必要かつ十分である.

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