Micro-RNA 10a Is Increased in Feline T Regulatory Cells and Increases Foxp3 Protein Expression Following In Vitro Transfection.

Yan Wang,Joanne L Tuohy,Jonathan E Fogle,Mukta Nag

doi:10.3390/vetsci4010012

Yan Wang, Joanne L Tuohy + Show 2 more

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https://doi.org/10.3390/vetsci4010012

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Abstract

CD4+CD25+Foxp3+ T regulatory (Treg) cells are activated during the course of lentiviral infection and exhibit heightened suppressor function when compared to Treg cells from uninfected controls. Foxp3 is essential to Treg cell function and multiple studies have documented that lentivirus-activated Treg cells exhibit heightened Foxp3 expression when compared to Treg cells from uninfected controls. Our hypothesis was that lentivirus-induced micro-RNAs (miRNAs) contribute to heightened Treg cell suppressor function by stabilizing Foxp3 expression. We demonstrated that CD4+CD25+ T cells from both feline immunodeficiency virus infected (FIV+) cats and uninfected control cats exhibit increased miRNA 10a and 21 levels compared to autologous CD4+CD25− T cells but there was no difference in the levels of these miRNAs when Treg cells from FIV+ cats were compared to Treg cells from uninfected controls. Further, there was no increase in Foxp3 mRNA following transfection of miRNA 10a or 21 into a feline cell line. However, transfection with miRNA 10a resulted in increased Foxp3 protein expression.

Highlights

T regulatory (Treg) cells, first identified as a subpopulation of CD4+ T cells expressing the IL2α receptor (CD25), play a major role in suppressing autoimmune T cell responses [1,2]
It has been clearly demonstrated that Treg cells are activated during the course of lentiviral infection and exhibit heightened suppressor function when compared to Treg cells from uninfected controls [5,6,7,8]
Foxp3 messenger RNA (mRNA) Is Increased in CD4+ CD25+ Treg Cells during FIV Infection

Summary

Introduction

T regulatory (Treg) cells, first identified as a subpopulation of CD4+ T cells expressing the IL2α receptor (CD25), play a major role in suppressing autoimmune T cell responses [1,2]. It has been clearly demonstrated that Treg cells are activated during the course of lentiviral infection and exhibit heightened suppressor function when compared to Treg cells from uninfected controls [5,6,7,8]. The forkhead transcription factor Foxp, is essential to Treg cell development and function [9,10]. Treg cell Foxp expression is normally under tight epigenetic (DNA methylation and demethylation) and post-transcriptional (micro-RNA, miRNA) control. Many investigations have clearly demonstrated that demethylation of the promoter region and the Treg-specific demethylated region (TSDR) in the Foxp gene lead to sustained, high levels of Foxp messenger RNA (mRNA) [11,12]

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Conclusion