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

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

84 Scopus citations


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.

Original languageEnglish
Pages (from-to)83-93
Number of pages11
Issue number1
StatePublished - 19 07 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc.


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