Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells
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 suppressi...
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doaj-743de4152c564e59b634c5b49edf2b2c2020-11-25T03:40:01ZengElsevierCell Reports2211-12472018-02-012282094210610.1016/j.celrep.2018.01.070Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells Ubaid Ullah0Syed Bilal Ahmad Andrabi1Subhash Kumar Tripathi2Obaiah Dirasantha3Kartiek Kanduri4Sini Rautio5Catharina C. Gross6Sari Lehtimäki7Kanchan Bala8Johanna Tuomisto9Urvashi Bhatia10Deepankar Chakroborty11Laura L. Elo12Harri Lähdesmäki13Heinz Wiendl14Omid Rasool15Riitta Lahesmaa16Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, FinlandTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, FinlandTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, FinlandTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, FinlandTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; Department of Computer Science, Aalto University School of Science, Aalto, FinlandDepartment of Computer Science, Aalto University School of Science, Aalto, FinlandDepartment of Neurology, University of Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster, GermanyTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, FinlandTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, FinlandTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, FinlandDepartment of Neurology, University of Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster, GermanyTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, FinlandTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, FinlandTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; Department of Computer Science, Aalto University School of Science, Aalto, FinlandDepartment of Neurology, University of Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster, GermanyTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, FinlandTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124718301190iTregsuppressionHIC1FOXP3regulatory SNPRNA-seq |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells Cell Reports iTreg suppression HIC1 FOXP3 regulatory SNP RNA-seq |
author_facet |
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 |
author_sort |
Ubaid Ullah |
title |
Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells |
title_short |
Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells |
title_full |
Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells |
title_fullStr |
Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells |
title_full_unstemmed |
Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells |
title_sort |
transcriptional repressor hic1 contributes to suppressive function of human induced regulatory t cells |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-02-01 |
description |
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. |
topic |
iTreg suppression HIC1 FOXP3 regulatory SNP RNA-seq |
url |
http://www.sciencedirect.com/science/article/pii/S2211124718301190 |
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