Beta-catenin stabilization extends regulatory T cell survival and induces anergy in nonregulatory T cells.
Beta-catenin is a central molecule in the Wnt pathway. Expression of a stable form of beta-catenin on CD4+CD25+ regulatory T (T(reg)) cells resulted in a marked enhancement of survival of these cells in vitro. Furthermore, stable beta-catenin-expressing CD4+CD25+ T(reg) cells outcompeted control T(reg) cells in vivo, and the number of T(reg) cells necessary for protection against inflammatory bowel disease could be substantially reduced when stable beta-catenin-expressing CD4+CD25+ T(reg) cells were used instead of control T(reg) cells. Expression of stable beta-catenin on potentially pathogenic CD4+CD25- T cells rendered these cells anergic, and the beta-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, beta-catenin stabilization has a powerful effect on the prevention of inflammatory disease.
Ding
Yi
Y
Molecular Pathogenesis Program and Skirball Institute for Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.
Shen
Shiqian
S
Lino
Andreia C
AC
Curotto de Lafaille
Maria A
MA
Lafaille
Juan J
JJ
D000818:Animals; D002470:Cell Survival; D017635:Clonal Anergy / Q000276:immunology*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*; D013816:Thermodynamics; D014161:Transduction, Genetic; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
D053645:Interleukin-2 Receptor alpha Subunit; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D051176:beta Catenin