β-カテニンの安定化は調節性T細胞の生存を延長し、非調節性T細胞のアネルギーを誘導する

（nature medicine 2月号Vol.14 No.1 / P. 162 - 169）

β-カテニンは、Wnt経路の重要な分子。
in vitroでは、CD4+CD25+調節性T（Treg）細胞での
安定型β-カテニンの発現によって、これらの細胞の生存が著しく促進。

in vivoでは、安定型β-カテニンを発現するCD4+CD25+Treg細胞は、
対照のTreg細胞との競合に打ち勝ち、
安定型β-カテニンを発現するCD4+CD25+Treg細胞を用いると、
炎症性腸疾患の防御に必要なTreg細胞の数を大幅に減らす。

疾患発症の原因となる可能性があるCD4+CD25-T細胞上に、
安定型β-カテニンを発現させると、アネルギー状態が生じた。
β-カテニンを介したアネルギー誘導は、Foxp3欠損T細胞でも起こった。

β-カテニンの安定化は、既存の調節性T細胞の生存促進と
エフェクターT細胞前駆細胞での非反応性誘導によって、
炎症性疾患の防止に強力な影響を及ぼす。

[原文]
Beta-catenin stabilization extends regulatory T cell survival and induces anergy in nonregulatory T cells

Yi Ding1,2, Shiqian Shen1, Andreia C Lino1, Maria A Curotto de Lafaille1,3 & Juan J Lafaille1,3
1 Molecular Pathogenesis Program and Skirball Institute for Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.
2 Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.
3 Department of Pathology, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.

β-catenin is a central molecule in the Wnt pathway. Expression of a stable form of β-catenin on CD4+CD25+ regulatory T (Treg) cells resulted in a marked enhancement of survival of these cells in vitro. Furthermore, stable β-catenin-expressing CD4+CD25+ Treg cells outcompeted control Treg cells in vivo, and the number of Treg cells necessary for protection against inflammatory bowel disease could be substantially reduced when stable β-catenin-expressing CD4+CD25+Treg cells were used instead of control Treg cells. Expression of stable β-catenin on potentially pathogenicCD4+CD25-T cells rendered these cells anergic, and the β-catenin-mediated induction of anergy occurred even in Foxp3-deficient T cells. Thus, through enhanced survival of existing regulatory T cells, and through induction of unresponsiveness in precursors of T effector cells, β-catenin stabilization has a powerful effect on the prevention of inflammatory disease.

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