Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells.

Cell Reports
Ubaid UllahRiitta Lahesmaa

Abstract

Regulatory T (Treg) cells are critical in regulating the immune response. In vitro induced Treg (iTreg) cells have significant potential in clinical medicine. However, applying iTreg cells as therapeutics is complicated by the poor stability of human iTreg cells and their variable suppressive activity. Therefore, it is important to understand the molecular mechanisms of human iTreg cell specification. We identified hypermethylated in cancer 1 (HIC1) as a transcription factor upregulated early during the differentiation of human iTreg cells. Although FOXP3 expression was unaffected, HIC1 deficiency led to a considerable loss of suppression by iTreg cells with a concomitant increase in the expression of effector T cell associated genes. SNPs linked to several immune-mediated disorders were enriched around HIC1 binding sites, and in vitro binding assays indicated that these SNPs may alter the binding of HIC1. Our results suggest that HIC1 is an important contributor to iTreg cell development and function.

Citations

May 17, 2018·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·R E HoeppliM K Levings
Jun 8, 2018·Bioinformatics·Kari NousiainenHarri Lähdesmäki
Jan 26, 2021·Frontiers in Cellular and Infection Microbiology·Biana BernshteinMichal Schwartz
May 22, 2019·Seminars in Cell & Developmental Biology·Desh Deepak SinghSubhash K Tripathi

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Datasets Mentioned

BETA
GSE25087
GSE41229

Methods Mentioned

BETA
RNA-seq
PMA
Immunoprecipitation
ChIP-seq
Assay

Software Mentioned

TRANSFAC
MACS
Homer
GSEA
iTreg
HTSeq
Ingenuity Pathway Analysis ( IPA
tophat2

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