Cutting Edge: The Foxp3 Target miR-155 Contributes to the Development of Regulatory T Cells

Abstract

Foxp3 is a transcription factor that is essential for the normal development of regulatory T cells (Tregs). In the absence of microRNAs (miRNAs), Foxp3+ Tregs develop but fail to maintain immune homeostasis, leading to a scurfy-like disease. Global analysis of the network of genes regulated by Foxp3 has identified the miRNA miR-155, which is highly expressed in Tregs, as a direct target of Foxp3. In this study we report that miR-155-deficient mice have reduced numbers of Tregs, both in the thymus and periphery, due to impaired development. However, we found no evidence for defective suppressor activity of miR-155-deficient Tregs, either in vitro or in vivo. Our results indicate that miR-155 contributes to Treg development, but that additional miRNAs control Treg function.

The altered expression of inflammation-related microRNAs with microRNA-155 expression correlates with Th17 differentiation in patients with acute coronary syndrome

“…32 Furthermore, the proportion and the absolute number of Treg cells were also smaller in miR-155-deficient mice. 19,33 In summary, these studies indicated that miR-155 is essential for the differentiation of Th cell subsets. However, different transcripts were found to be targeted by miR-155 in different Th cell subsets, and additional targets still need to be confirmed.…”

MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis

“…However, miR-141 and Treg numbers were shown to fluctuate in relapsing and remitting phases of multiple sclerosis (Naghavian et al, 2015). In addition, miRNAs, such has miR-155, which regulate normal Treg development and function (Lu et al, 2009;Gao et al, 2012;Josefowicz et al, 2012;Dooley et al, 2013;Kohlhaas et al, 2009), were not found to be altered in the naïve CD4 T cells of patients with multiple sclerosis (Guerau-de-Arellano et al, 2011). Thus, it is important to determine if these TGFb-targeting miRNAs have roles in normal Treg development that are dysregulated in patients with multiple sclerosis.…”

Unravelling the molecular basis for regulatory T‐cell plasticity and loss of function in disease

“…The modifiable mediators of this regulation include methylation,37, 38, 39, 40, 41, 42, 43, 44 acetylation45, 46, 47 and microRNA‐mediated control of transcript translation 28, 48, 49, 50, 51, 52, 53, 54, 55. The global regulation of FOXP3 is influenced by chromatin organises, including SATB1 acts both during development and in mature cells 48, 58.…”