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

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

doi:10.1016/j.celrep.2018.01.070

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

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

Turku Bioscience Centre

Research output: Contribution to journal › Article › Scientific › peer-review

35 Citations (Scopus)

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.

Original language	Undefined/Unknown
Pages (from-to)	2094–2106
Number of pages	13
Journal	Cell Reports
Volume	22
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2018.01.070
Publication status	Published - 2018
MoE publication type	A1 Journal article-refereed

Access to Document

10.1016/j.celrep.2018.01.070

https://www.sciencedirect.com/science/article/pii/S2211124718301190

Cite this

Ullah, U., Bilal Ahmad Andrabi, S., Kumar Tripathi, S., 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, 22(8), 2094–2106. https://doi.org/10.1016/j.celrep.2018.01.070

@article{6ce24e38648c4b2695be1042b5f4870e,

title = "Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells",

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.",

author = "Ubaid Ullah and {Bilal Ahmad Andrabi}, Syed and {Kumar Tripathi}, Subhash and Obaiah Dirasantha and Kartiek Kanduri and Sini Rautio and Gross, {Catharina C.} and Sari Lehtim{\"a}ki and Kanchan Bala and Johanna Tuomisto and Urvashi Bhatia and Deepankar Chakroborty and Elo, {Laura L.} and Harri L{\"a}hdesm{\"a}ki and Heinz Wiendl and Omid Rasool and Riitta Lahesmaa",

year = "2018",

doi = "10.1016/j.celrep.2018.01.070",

language = "Odefinierat/ok{\"a}nt",

volume = "22",

pages = "2094–2106",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "8",

}

Ullah, U, Bilal Ahmad Andrabi, S, Kumar Tripathi, S, Dirasantha, O, Kanduri, K, Rautio, S, Gross, CC, Lehtimäki, S, Bala, K, Tuomisto, J, Bhatia, U, Chakroborty, D, Elo, LL, 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

TY - JOUR

T1 - Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells

AU - Ullah, Ubaid

AU - Bilal Ahmad Andrabi, Syed

AU - Kumar Tripathi, Subhash

AU - Dirasantha, Obaiah

AU - Kanduri, Kartiek

AU - Rautio, Sini

AU - Gross, Catharina C.

AU - Lehtimäki, Sari

AU - Bala, Kanchan

AU - Tuomisto, Johanna

AU - Bhatia, Urvashi

AU - Chakroborty, Deepankar

AU - Elo, Laura L.

AU - Lähdesmäki, Harri

AU - Wiendl, Heinz

AU - Rasool, Omid

AU - Lahesmaa, Riitta

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2018.01.070

DO - 10.1016/j.celrep.2018.01.070

M3 - Artikel

SN - 2211-1247

VL - 22

SP - 2094

EP - 2106

JO - Cell Reports

JF - Cell Reports

IS - 8

ER -