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

Autor: Urvashi Bhatia, Catharina C. Gross, Harri Lähdesmäki, Kanchan Bala, Deepankar Chakroborty, Syed Bilal Ahmad Andrabi, Subhash K. Tripathi, Kartiek Kanduri, Johanna Tuomisto, Sari Lehtimäki, Heinz Wiendl, Sini Rautio, Omid Rasool, Obaiah Dirasantha, Ullah Ubaid Ullah, Laura L. Elo, Riitta Lahesmaa
Přispěvatelé: Åbo Akademi University, Department of Computer Science, Professorship Lähdesmäki Harri, University of Münster, Aalto-yliopisto, Aalto University
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Transcription
Genetic
FOXP3
Cell
Kruppel-Like Transcription Factors
T cells
Polymorphism
Single Nucleotide
T-Lymphocytes
Regulatory
Article
General Biochemistry
Genetics and Molecular Biology
Autoimmune Diseases
03 medical and health sciences
0302 clinical medicine
Immune system
Downregulation and upregulation
Transcriptional regulation
medicine
Humans
Cell Lineage
transcriptional regulation
ta318
regulatory SNP
Transcription factor
lcsh:QH301-705.5
iTreg
ta113
expression kinetics
Binding Sites
Genome
Human
Sequence Analysis
RNA
Effector
Cell growth
Gene Expression Profiling
Cell Differentiation
DNA
HIC1
suppression
3. Good health
Cell biology
Repressor Proteins
ChIP-seq
030104 developmental biology
medicine.anatomical_structure
lcsh:Biology (General)
RNA-seq
Transcriptome
030217 neurology & neurosurgery
Protein Binding
Zdroj: Cell Reports, Vol 22, Iss 8, Pp 2094-2106 (2018)
Cell Reports
ISSN: 2211-1247
Popis: 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.
Graphical Abstract
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
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.
Databáze: OpenAIRE
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