MicroRNA-17 Modulates Regulatory T Cell Function by Targeting Co-regulators of the Foxp3 Transcription Factor

Huang Yu Yang, Joseph Barbi, Chao Yi Wu, Ying Zheng, Paolo D A Vignali, Xingmei Wu, Jin Hui Tao, Benjamin V. Park, Shashika Bandara, Lewis Novack, Xuhao Ni, Xiaoping Yang, Kwang Yu Chang, Ren Chin Wu, Junran Zhang, Chih Wei Yang, Drew M. Pardoll, Huabin Li, Fan Pan

Research output: Research - peer-reviewArticle

Abstract

Regulatory T (Treg) cells are important in maintaining self-tolerance and immune homeostasis. The Treg cell transcription factor Foxp3 works in concert with other co-regulatory molecules, including Eos, to determine the transcriptional signature and characteristic suppressive phenotype of Treg cells. Here, we report that the inflammatory cytokine interleukin-6 (IL-6) actively repressed Eos expression through microRNA-17 (miR-17). miR-17 expression increased in Treg cells in the presence of IL-6, and its expression negatively correlated with that of Eos. Treg cell suppressive activity was diminished upon overexpression of miR-17 in vitro and in vivo, which was mitigated upon co-expression of an Eos mutant lacking miR-17 target sites. Also, RNAi of miR-17 resulted in enhanced suppressive activity. Ectopic expression of miR-17 imparted effector-T-cell-like characteristics to Treg cells via the de-repression of genes encoding effector cytokines. Thus, miR-17 provides a potent layer of Treg cell control through targeting Eos and additional Foxp3 co-regulators.

LanguageEnglish (US)
Pages83-93
Number of pages11
JournalImmunity
Volume45
Issue number1
DOIs
StatePublished - Jul 19 2016

Fingerprint

Regulatory T-Lymphocytes
MicroRNAs
Transcription Factors
Interleukin-6
Cytokines
Self Tolerance
RNA Interference
Homeostasis
T-Lymphocytes
Phenotype
Genes
In Vitro Techniques
Ectopic Gene Expression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

MicroRNA-17 Modulates Regulatory T Cell Function by Targeting Co-regulators of the Foxp3 Transcription Factor. / Yang, Huang Yu; Barbi, Joseph; Wu, Chao Yi; Zheng, Ying; Vignali, Paolo D A; Wu, Xingmei; Tao, Jin Hui; Park, Benjamin V.; Bandara, Shashika; Novack, Lewis; Ni, Xuhao; Yang, Xiaoping; Chang, Kwang Yu; Wu, Ren Chin; Zhang, Junran; Yang, Chih Wei; Pardoll, Drew M.; Li, Huabin; Pan, Fan.

In: Immunity, Vol. 45, No. 1, 19.07.2016, p. 83-93.

Research output: Research - peer-reviewArticle

Yang, HY, Barbi, J, Wu, CY, Zheng, Y, Vignali, PDA, Wu, X, Tao, JH, Park, BV, Bandara, S, Novack, L, Ni, X, Yang, X, Chang, KY, Wu, RC, Zhang, J, Yang, CW, Pardoll, DM, Li, H & Pan, F 2016, 'MicroRNA-17 Modulates Regulatory T Cell Function by Targeting Co-regulators of the Foxp3 Transcription Factor' Immunity, vol 45, no. 1, pp. 83-93. DOI: 10.1016/j.immuni.2016.06.022
Yang HY, Barbi J, Wu CY, Zheng Y, Vignali PDA, Wu X et al. MicroRNA-17 Modulates Regulatory T Cell Function by Targeting Co-regulators of the Foxp3 Transcription Factor. Immunity. 2016 Jul 19;45(1):83-93. Available from, DOI: 10.1016/j.immuni.2016.06.022
Yang, Huang Yu ; Barbi, Joseph ; Wu, Chao Yi ; Zheng, Ying ; Vignali, Paolo D A ; Wu, Xingmei ; Tao, Jin Hui ; Park, Benjamin V. ; Bandara, Shashika ; Novack, Lewis ; Ni, Xuhao ; Yang, Xiaoping ; Chang, Kwang Yu ; Wu, Ren Chin ; Zhang, Junran ; Yang, Chih Wei ; Pardoll, Drew M. ; Li, Huabin ; Pan, Fan. / MicroRNA-17 Modulates Regulatory T Cell Function by Targeting Co-regulators of the Foxp3 Transcription Factor. In: Immunity. 2016 ; Vol. 45, No. 1. pp. 83-93
@article{df19952d1e084d6abfbe3ed16b5d5281,
title = "MicroRNA-17 Modulates Regulatory T Cell Function by Targeting Co-regulators of the Foxp3 Transcription Factor",
abstract = "Regulatory T (Treg) cells are important in maintaining self-tolerance and immune homeostasis. The Treg cell transcription factor Foxp3 works in concert with other co-regulatory molecules, including Eos, to determine the transcriptional signature and characteristic suppressive phenotype of Treg cells. Here, we report that the inflammatory cytokine interleukin-6 (IL-6) actively repressed Eos expression through microRNA-17 (miR-17). miR-17 expression increased in Treg cells in the presence of IL-6, and its expression negatively correlated with that of Eos. Treg cell suppressive activity was diminished upon overexpression of miR-17 in vitro and in vivo, which was mitigated upon co-expression of an Eos mutant lacking miR-17 target sites. Also, RNAi of miR-17 resulted in enhanced suppressive activity. Ectopic expression of miR-17 imparted effector-T-cell-like characteristics to Treg cells via the de-repression of genes encoding effector cytokines. Thus, miR-17 provides a potent layer of Treg cell control through targeting Eos and additional Foxp3 co-regulators.",
author = "Yang, {Huang Yu} and Joseph Barbi and Wu, {Chao Yi} and Ying Zheng and Vignali, {Paolo D A} and Xingmei Wu and Tao, {Jin Hui} and Park, {Benjamin V.} and Shashika Bandara and Lewis Novack and Xuhao Ni and Xiaoping Yang and Chang, {Kwang Yu} and Wu, {Ren Chin} and Junran Zhang and Yang, {Chih Wei} and Pardoll, {Drew M.} and Huabin Li and Fan Pan",
year = "2016",
month = "7",
doi = "10.1016/j.immuni.2016.06.022",
volume = "45",
pages = "83--93",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - MicroRNA-17 Modulates Regulatory T Cell Function by Targeting Co-regulators of the Foxp3 Transcription Factor

AU - Yang,Huang Yu

AU - Barbi,Joseph

AU - Wu,Chao Yi

AU - Zheng,Ying

AU - Vignali,Paolo D A

AU - Wu,Xingmei

AU - Tao,Jin Hui

AU - Park,Benjamin V.

AU - Bandara,Shashika

AU - Novack,Lewis

AU - Ni,Xuhao

AU - Yang,Xiaoping

AU - Chang,Kwang Yu

AU - Wu,Ren Chin

AU - Zhang,Junran

AU - Yang,Chih Wei

AU - Pardoll,Drew M.

AU - Li,Huabin

AU - Pan,Fan

PY - 2016/7/19

Y1 - 2016/7/19

N2 - Regulatory T (Treg) cells are important in maintaining self-tolerance and immune homeostasis. The Treg cell transcription factor Foxp3 works in concert with other co-regulatory molecules, including Eos, to determine the transcriptional signature and characteristic suppressive phenotype of Treg cells. Here, we report that the inflammatory cytokine interleukin-6 (IL-6) actively repressed Eos expression through microRNA-17 (miR-17). miR-17 expression increased in Treg cells in the presence of IL-6, and its expression negatively correlated with that of Eos. Treg cell suppressive activity was diminished upon overexpression of miR-17 in vitro and in vivo, which was mitigated upon co-expression of an Eos mutant lacking miR-17 target sites. Also, RNAi of miR-17 resulted in enhanced suppressive activity. Ectopic expression of miR-17 imparted effector-T-cell-like characteristics to Treg cells via the de-repression of genes encoding effector cytokines. Thus, miR-17 provides a potent layer of Treg cell control through targeting Eos and additional Foxp3 co-regulators.

AB - Regulatory T (Treg) cells are important in maintaining self-tolerance and immune homeostasis. The Treg cell transcription factor Foxp3 works in concert with other co-regulatory molecules, including Eos, to determine the transcriptional signature and characteristic suppressive phenotype of Treg cells. Here, we report that the inflammatory cytokine interleukin-6 (IL-6) actively repressed Eos expression through microRNA-17 (miR-17). miR-17 expression increased in Treg cells in the presence of IL-6, and its expression negatively correlated with that of Eos. Treg cell suppressive activity was diminished upon overexpression of miR-17 in vitro and in vivo, which was mitigated upon co-expression of an Eos mutant lacking miR-17 target sites. Also, RNAi of miR-17 resulted in enhanced suppressive activity. Ectopic expression of miR-17 imparted effector-T-cell-like characteristics to Treg cells via the de-repression of genes encoding effector cytokines. Thus, miR-17 provides a potent layer of Treg cell control through targeting Eos and additional Foxp3 co-regulators.

UR - http://www.scopus.com/inward/record.url?scp=84990836182&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84990836182&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2016.06.022

DO - 10.1016/j.immuni.2016.06.022

M3 - Article

VL - 45

SP - 83

EP - 93

JO - Immunity

T2 - Immunity

JF - Immunity

SN - 1074-7613

IS - 1

ER -