Thymic regulatory T cell development: role of signalling pathways and transcription factors

Abstract

Regulatory T cells (Tregs) are a subset of CD4 T cells that are key mediators of immune tolerance. Most Tregs develop in the thymus. In this review we summarise recent findings on the role of diverse signalling pathways and downstream transcription factors in thymic Treg development.

Figure 1

The stages of tTreg development. Thymic Treg development is achieved in two stages. Initially, postpositive selected thymocytes undergo TCR and CD28 dependent maturation into a Foxp3⁻ tTreg precursor population. A subsequent IL-2 dependent step leads to the development of Foxp3 expressing mature tTregs.

Figure 2

Transcription factors in tTreg development. Once engaged, cell surface receptors initiate c-Rel activation and nuclear entry. c-Rel binding to the Foxp3 promoter and Cns elements promotes epigenetic changes, including demethylation and chromatin remodelling (not pictured) of the Foxp3 locus. Several other transcription factors cooperate with c-Rel to initiate and preserve the stable expression of Foxp3 in tTregs.