Nature Medicine：β-连环蛋白稳定表达可延长调节性T细胞寿命

美国纽约大学医学院Ding等在《自然医学》杂志上报道，β-连环蛋白（Beta-catenin）稳定表达可延长调节性T细胞(regulatory T cell)寿命
Wnt通路的组成主要包括:细胞外因子Wnt、跨膜受体卷曲蛋白、散乱蛋白、结肠腺瘤样息肉病基因产物、β-连环蛋白及T细胞因子/淋巴样增强因子等一系列蛋白。
β-连环蛋白是Wnt通路的关键分子。在体外试验中，CD4+CD25+调节性T细胞稳定表达β-连环蛋白，可显著延长细胞寿命。在炎症性肠病治疗中，若CD4+CD25+调节性T细胞稳定表达β-连环蛋白，则可以保留必要的调节性T细胞起到保护作用，而非一味地控制T细胞数量。对于非调节性T细胞（CD4+CD25- T细胞、Foxp3-缺陷 T细胞）而言，稳定表达β-连环蛋白可诱导其不应答。
所以，研究人员认为，通过延长调节性T细胞寿命和诱导T效应细胞前体不应答，β-连环蛋白将对炎症性疾病的预防产生重要影响。（医学空间）
生物谷推荐原始出处：
Nature Medicine 14, 162 - 169 (2008)
Published online: 3 February 2008 | doi:10.1038/nm1707
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
Abstract
-catenin is a central molecule in the Wnt pathway. Expression of a stable form of -catenin on CD4+CD25+ regulatory T (Treg) cells resulted in a marked enhancement of survival of these cells in vitro. Furthermore, stable -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 -catenin–expressing CD4+CD25+ Treg cells were used instead of control Treg cells. Expression of stable -catenin on potentially pathogenic CD4+CD25- T cells rendered these cells anergic, and the -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, -catenin stabilization has a powerful effect on the prevention of inflammatory disease.
Molecular Pathogenesis Program and Skirball Institute for Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.
Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.
Department of Pathology, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.
Correspondence to: Juan J Lafaille1,3 e-mail: lafaille@saturn.med.nyu.edu