Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1

Masahiro Ono, Hiroko Yaguchi, Naganari Ohkura, Issay Kitabayashi, Yuko Nagamura, Takashi Nomura, Yoshiki Miyachi, Toshihiko Tsukada, Shimon Sakaguchi

Research output: Contribution to journalArticlepeer-review

540 Citations (Scopus)

Abstract

Naturally arising CD25+CD4+ regulatory T cells (TR cells) are engaged in the maintenance of immunological self-tolerance and immune homeostasis by suppressing aberrant or excessive immune responses, such as autoimmune disease and allergy. TR cells specifically express the transcription factor Foxp3, a key regulator of T R-cell development and function. Ectopic expression of Foxp3 in conventional T cells is indeed sufficient to confer suppressive activity, repress the production of cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-γ), and upregulate TR-cell-associated molecules such as CD25, cytotoxic T-lymphocyte-associated antigen-4, and glucocorticoid-induced TNF-receptor-family-related protein. However, the method by which Foxp3 controls these molecular events has yet to be explained. Here we show that the transcription factor AML1 (acute myeloid leukaemia 1)/Runx1 (Runt-related transcription factor 1), which is crucially required for normal haematopoiesis including thymic T-cell development, activates IL-2 and IFN-γ gene expression in conventional CD4+ T cells through binding to their respective promoters. In natural TR cells, Foxp3 interacts physically with AML1. Several lines of evidence support a model in which the interaction suppresses IL-2 and IFN-γ production, upregulates TR-cell-associated molecules, and exerts suppressive activity. This transcriptional control of TR-cell function by an interaction between Foxp3 and AML1 can be exploited to control physiological and pathological T-cell-mediated immune responses.

Original languageEnglish
Pages (from-to)685-689
Number of pages5
JournalNature
Volume446
Issue number7136
DOIs
Publication statusPublished - 05-04-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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