A novel role for KLF14 in T regulatory cell differentiation

Cellular and Molecular Gastroenterology and Hepatology
Olga F SarmentoWilliam A Faubion

Abstract

KLF proteins function as epigenetic reprogramming factors during cell differentiation in many cell populations and in engineered iPS cells. In this study, we determined KLF14 function in the regulation of FOXP3, a transcription factor critical for Treg cell differentiation. We studied the effects of KLF14 on FOXP3 expression at the level of the protein and mRNA. We evaluated the functional relevance of KLF14 to FOXP3(+) Treg cells in vitro and in vivo through suppression assays and two colitis models. Finally, we analyzed the effect of KLF14 on the epigenetic landscape of the FOXP3 promoter locus through chromatin immuno-precipitation. KLF14, induced upon activation of naïve CD4(+) T cells, segregates to the FOXP3(-) population and is inversely associated with FOXP3 expression and Treg function. KLF14 KO CD4(+) cells differentiated into adaptive Tregs more readily in vitro and in vivo. KLF14 KO cells demonstrated enhanced Treg suppressor function in vitro and in vivo. KLF14 repressed FOXP3 at the level of the mRNA and protein, and by ChIP assay KLF14 was found to bind to the TSDR enhancer region of FOXP3. Furthermore, loss of KLF14 reduced the levels of H3K9me3, HP1 and Suv39H1at the TSDR. These results outline a novel mechanis...Continue Reading

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Citations

Sep 15, 2015·The Journal of Clinical Investigation·Yanhong GuoY Eugene Chen
Apr 8, 2017·Epigenetics : Official Journal of the DNA Methylation Society·Nicholas D JohnsonKaren N Conneely
Jun 18, 2020·Frontiers in Cardiovascular Medicine·Qianyi Yang, Mete Civelek
Jun 1, 2018·Oxidative Medicine and Cellular Longevity·Michalina WezykCezary Żekanowski
Sep 27, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Xiaoyan ChenBo Wang
Jan 4, 2021·Biochemical Genetics·Ensieh ShahvazianMasoud Mirzaei
Jan 8, 2021·Journal of the American Heart Association·Joshua A UhlornHeddwen L Brooks

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Methods Mentioned

BETA
PCRs
PCR
electrophoresis
immunoprecipitation
ChIP
transgenic
FACS
biopsy
flow cytometry
fluorescence-activated cell sorting

Software Mentioned

MAP
VisionWorks
Bioconductor
JMP
RSeq
edgeR

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