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

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Journal Title
Journal ISSN
Volume Title
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Date
2018-02-20
Major/Subject
Mcode
Degree programme
Language
en
Pages
13
2094-2106
Series
Cell Reports, Volume 22, issue 8
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. Ullah et al. find that HIC1 is induced during human iTreg cell differentiation. HIC1 binds to and regulates the expression of key genes during iTreg differentiation. Several autoimmune-disease-associated SNPs are enriched near HIC1 ChIP-seq peaks.
Description
Keywords
ChIP-seq, expression kinetics, FOXP3, HIC1, iTreg, regulatory SNP, RNA-seq, suppression, T cells, transcriptional regulation
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Citation
Ubaid Ullah , U , Andrabi , S B A , Tripathi , S K , Dirasantha , O , Kanduri , K , Rautio , S , Gross , C C , Lehtimäki , S , Bala , K , Tuomisto , J , Bhatia , U , Chakroborty , D , Elo , L L , Lähdesmäki , H , Wiendl , H , Rasool , O & Lahesmaa , R 2018 , ' Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells ' , Cell Reports , vol. 22 , no. 8 , pp. 2094-2106 . https://doi.org/10.1016/j.celrep.2018.01.070