Cell Reports
Volume 22, Issue 8, 20 February 2018, Pages 2094-2106
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Article
Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells

https://doi.org/10.1016/j.celrep.2018.01.070Get rights and content
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Highlights

  • Hypermethylated in cancer 1 (HIC1) is upregulated in iTreg cells

  • HIC1-deficient iTreg cells express FOXP3 but have reduced suppressive ability

  • Autoimmune-disease-associated SNPs are enriched within HIC1 binding loci

  • HIC1 is an important regulator of iTreg development and function

Summary

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.

Keywords

iTreg
suppression
HIC1
FOXP3
regulatory SNP
RNA-seq
ChIP-seq
expression kinetics
T cells
transcriptional regulation

Cited by (0)

4

Present address: Hospital District of Helsinki and Uusimaa (HUS), Helsinki, Finland

5

Present address: Institut für Tumorbiologie und Experimentelle Therapie, Frankfurt am Main Sachsenhausen, Germany

6

These authors contributed equally

7

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