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

Research output: Contribution to journalArticle

Researchers

  • Ullah Ubaid Ullah
  • Syed Bilal Ahmad Andrabi
  • Subhash Kumar Tripathi
  • Obaiah Dirasantha
  • Kartiek Kanduri
  • Sini Rautio

  • Catharina C. Gross
  • Sari Lehtimäki
  • Kanchan Bala
  • Johanna Tuomisto
  • Urvashi Bhatia
  • Deepankar Chakroborty
  • Laura L. Elo
  • Harri Lähdesmäki

  • Heinz Wiendl
  • Omid Rasool
  • Riitta Lahesmaa

Research units

  • Åbo Akademi University
  • University of Münster
  • Hospital District of Helsinki and Uusimaa

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.

Details

Original languageEnglish
Pages (from-to)2094-2106
Number of pages13
JournalCell Reports
Volume22
Issue number8
Publication statusPublished - 20 Feb 2018
MoE publication typeA1 Journal article-refereed

    Research areas

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

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