Control of regulatory T-cell differentiation and function by T-cell receptor signalling and Foxp3 transcription factor complexes.

Control of regulatory T-cell differentiation and function by T-cell receptor signalling and Foxp3 transcription factor complexes. Immunology. 2020 Feb 05;: Authors: Ono M Abstract The transcription factor Foxp3 controls the differentiation and function of regulatory T-cells (Treg). Studies in the past decades identified numerous Foxp3-interacting protein partners. However, it is still not clear how Foxp3 produces the Treg-type transcriptomic landscape through cooperating with its partners. Here I show the current understanding of how Foxp3 transcription factor complexes regulate the differentiation, maintenance, and functional maturation of Treg. Importantly, T-cell receptor (TCR) signalling plays central roles in Treg differentiation and Foxp3-mediated gene regulation. Thus, differentiating Treg will have recognised their cognate antigens and received TCR signals before initiating Foxp3 transcription, which is triggered by TCR induced transcription factors including NFAT, AP-1, and NF-κB. Once expressed, Foxp3 seizes TCR signal-induced transcriptional and epigenetic mechanisms through interacting with is AML1/Runx1 and NFAT. Thus Foxp3 modifies gene expression dynamics of TCR-induced genes, which constitute cardinal mechanisms for Treg-mediated immune suppression. Next, I discuss the following key topics, proposing new mechanistic models for Foxp3-mediated gene regulation: (1) how Foxp3 transcription is induced and maintained by th...
Source: Immunology - Category: Allergy & Immunology Authors: Tags: Immunology Source Type: research