転写因子SOX13によるガンマデルタ対アルファベタTリンパ球の微分化の調整

Heather J Melichar¹, Kavitha Narayan, Sandy D Der

¹Department of Pathology, Graduate Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.

Science (New York, N.Y.)

|January 16, 2007

まとめ

Sox13はT細胞の発達を導く重要な転写因子です. ガンマデルタT細胞の発達を促し,アルファベタT細胞の分化を抑制し,リンパ球系統の決定における支配的な経路を明らかにする.

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.
発達生物学発達生物学とは

背景:

適応性免疫に不可欠なTリンパ球は,アルファベータとガンマデルタT細胞という2つの主要タイプに分けられます.
これらのT細胞系は,胸腺における共通の前駆体から生じるが,それらの分岐の分子調節体は,ほとんど不明のままである.

研究の目的:

アルファベータT細胞とガンマデルタT細胞の系統運命を決定する分子メカニズムを特定する.
T細胞発育における転写因子Sox13の役割を調査する.

主な方法:

T細胞発達におけるその機能を研究するために,SOX13トランスジェニックマウスを利用した.
T細胞系統へのコミットメントの必要性を評価するために,Sox13欠乏したマウスを生成し,分析しました.
Wnt/T細胞因子 (TCF) 信号伝達経路に対するSox13の影響を調査した.

主要な成果:

Sox13は,ガンマデルタT細胞特異遺伝子として特定されました.
Sox13の過剰発現は,ガンマデルタT細胞の発達を促し,アルファベータT細胞の分化を抑制した.
Sox13欠乏症は,アルファベータT細胞の発達に影響を与えることなく,ガンマデルタT細胞の発達障害を引き起こした.
Sox13は,Wnt/TCF経路を通じた信号伝達を阻害する.

結論:

Sox13は,ガンマデルタT細胞の系統を促進し,アルファベータT細胞の系統を阻害する重要な調節剤として作用します.
Wnt/TCF経路は,SOX13が系統決定機能を果たす重要なターゲットです.
これらの発見は,Tリンパ球の発達運命を制御する支配的な分子経路を明らかにしています.

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