The Ets-1 transcription factor controls the development and function of natural regulatory T cells. - Institut Pasteur Access content directly
Journal Articles Journal of Experimental Medicine Year : 2010

The Ets-1 transcription factor controls the development and function of natural regulatory T cells.

Abstract

Regulatory T cells (T reg cells) constitute a population of CD4(+) T cells that limits immune responses. The transcription factor Foxp3 is important for determining the development and function of T reg cells; however, the molecular mechanisms that trigger and maintain its expression remain incompletely understood. In this study, we show that mice deficient for the Ets-1 transcription factor (Ets-1(-/-)) developed T cell-mediated splenomegaly and systemic autoimmunity that can be blocked by functional wild-type T reg cells. Spleens of Ets-1(-/-) mice contained mostly activated T cells, including Th2-polarized CD4(+) cells and had reduced percentages of T reg cells. Splenic and thymic Ets-1(-/-) T reg cells expressed low levels of Foxp3 and displayed the CD103 marker that characterizes antigen-experienced T reg cells. Thymic development of Ets-1(-/-) T reg cells appeared intrinsically altered as Foxp3-expressing cells differentiate poorly in mixed fetal liver reconstituted chimera and fetal thymic organ culture. Ets-1(-/-) T reg cells showed decreased in vitro suppression activity and did not protect Rag2(-/-) hosts from naive T cell-induced inflammatory bowel disease. Furthermore, in T reg cells, Ets-1 interacted with the Foxp3 intronic enhancer and was required for demethylation of this regulatory sequence. These data demonstrate that Ets-1 is required for the development of natural T reg cells and suggest a role for this transcription factor in the regulation of Foxp3 expression.

Domains

Immunology

Dates and versions

pasteur-00528619 , version 1 (22-10-2010)

Identifiers

Cite

Enguerran Mouly, Karine Chemin, Hai Vu Nguyen, Martine Chopin, Laurent Mesnard, et al.. The Ets-1 transcription factor controls the development and function of natural regulatory T cells.. Journal of Experimental Medicine, 2010, 207 (10), pp.2113-25. ⟨10.1084/jem.20092153⟩. ⟨pasteur-00528619⟩
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