Transcriptional Control of Regulatory T cells

Abstract

Regulatory T cells (Tregs) constitute unique T cell lineage that plays a key role for immunological tolerance. Tregs are characterized by the expression of the forkhead box transcription factor Foxp3, which acts as a lineage-specifying factor by determining the unique suppression profile of these immune cells. Here, we summarize the recent progress in understanding how Foxp3 expression itself is epigenetically and transcriptionally controlled, how the Treg-specific signature is achieved and how unique properties of Treg subsets are defined by other transcription factors. Finally, we will discuss recent studies focusing on the molecular targeting of Tregs to utilize the specific properties of this unique cell type in therapeutic settings.

Oncogene-Expressing Senescent Melanocytes Up-Regulate MHC Class II, a Candidate Melanoma Suppressor Function

“…Remarkably, the top five gene ontologies represented in the up-regulated genes of Tyr-NRasQ61K nodes reflected increased antigen presentation and associated processes, such as endocytosis and vesicle-mediated transport ( Figure 5 h, 5 i). In principle, T-cell expansion and antigen presentation in lymph nodes of Tyr-NrasQ61K mice could be associated with immune activation or induction of immune tolerance, the latter by activation of regulatory T cells ( Delacher et al., 2014 ). To distinguish between these possibilities, we stained lymph nodes for expression of FoxP3, a transcription factor expressed by regulatory T cells ( Delacher et al., 2014 ).…”

Foxp3+ T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation

“…7,8 Together with the notion that Tregs having different origins or anatomical locations display distinct but specific gene expression profiles, 9 this has led to the discovery of different functional Treg subpopulations, termed ''effector'' Treg lineages. 10,11 Interestingly, recent reports indicate that Foxp3 þ Tregs can coopt the expression of specific transcription factors that are associated with the differentiation and function of effector CD4 þ T-cell lineages. In the context of T helper type 1 (Th1)-mediated inflammation, Tregs can upregulate the Th1-specific transcription factor T-bet, leading to the expression of CXCR3 and the accumulation of Foxp3 þ T-bet þ Tregs at sites of inflammation.…”

Comparative Analysis of Protocols to Induce Human CD4+Foxp3+ Regulatory T Cells by Combinations of IL-2, TGF-beta, Retinoic Acid, Rapamycin and Butyrate

“…Significant progress has been made in elucidating the regulation of Foxp3 expression. Activation of the Foxp3 gene is achieved by binding of several TFs to its promoter and intronic Conserved Non-coding DNA Sequences (CNSs) [ 8 , 9 ]. These TFs are activated via T cell receptor (TCR), IL-2 and TGF-β signaling and, depending on which CNS they act on, are implicated in either Foxp3 induction (CNS3), maintenance (CNS2) or TGF-β-enhanced expression (CNS1).…”