Foxo proteins cooperatively control the differentiation of Foxp3+ regulatory T cells. Academic Article uri icon

Overview

abstract

  • CD4(+) regulatory T cells (T(reg) cells) characterized by expression of the transcription factor Foxp3 have a pivotal role in maintaining immunological tolerance. Here we show that mice with T cell-specific deletion of both the Foxo1 and Foxo3 transcription factors (collectively called 'Foxo proteins' here) developed a fatal multifocal inflammatory disorder due in part to T(reg) cell defects. Foxo proteins functioned in a T(reg) cell-intrinsic manner to regulate thymic and transforming growth factor-beta (TGF-beta)-induced Foxp3 expression, in line with the ability of Foxo proteins to bind to Foxp3 locus and control Foxp3 promoter activity. Transcriptome analyses showed that Foxo proteins regulated the expression of additional T(reg) cell-associated genes and were essential for inhibiting the acquisition of effector T cell characteristics by T(reg) cells. Thus, Foxo proteins have crucial roles in specifying the T(reg) cell lineage.

publication date

  • May 13, 2010

Research

keywords

  • Cell Differentiation
  • Forkhead Transcription Factors
  • T-Lymphocytes, Regulatory
  • Thymus Gland

Identity

Scopus Document Identifier

  • 77953811224

Digital Object Identifier (DOI)

  • 10.1038/ni.1884

PubMed ID

  • 20467422

Additional Document Info

volume

  • 11

issue

  • 7