MiR-125a-5p Decreases the Sensitivity of Treg cells Toward IL-6-Mediated Conversion by Inhibiting IL-6R and STAT3 Expression

Dan Li; Chao Kong; Andy Tsun; Chen Chen; Huihui Song; Guochao Shi; Wen Pan; Dai Dai; Nan Shen; Bin Li

doi:10.1038/srep14615

MiR-125a-5p Decreases the Sensitivity of Treg cells Toward IL-6-Mediated Conversion by Inhibiting IL-6R and STAT3 Expression

Sci Rep. 2015 Oct 1:5:14615. doi: 10.1038/srep14615.

Authors

Dan Li¹, Chao Kong^{1

2}, Andy Tsun¹, Chen Chen¹, Huihui Song³, Guochao Shi³, Wen Pan^{4

5

6}, Dai Dai^{4

5}, Nan Shen^{4

5

7}, Bin Li¹

Affiliations

¹ Key Laboratory of Molecular Virology &Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
² Shanghai Key Laboratory of Bio-energy Crops, College of Life Science, Shanghai University, Shanghai 200444, China.
³ Department of Pulmonary Medicine, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
⁴ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁵ Joint Molecular Rheumatology Laboratory of the Institute of Health Sciences and Shanghai Renji Hospital, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
⁶ Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
⁷ Division of Rheumatology and the Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Abstract

The transcription factor FOXP3 is essential for the differentiation and function of regulatory T cells (Treg). It is established that the transcription factor GATA-3 is induced in Treg cells under inflammatory conditions. GATA-3 stabilizes FOXP3 levels to avoid the differentiation of Treg cells into inflammatory-like T cells. The IL-6 signal pathway influences the sensitivity of Treg cells towards instability. The mechanism of GATA-3 in regulating FOXP3 and its relation to the IL-6 pathway remains unclear. Here we report how miR-125a-5p plays an important role in regulating the conversion of Treg cells by IL-6. miR-125a-5p expression is low in Treg cells under steady state conditions and can be induced by GATA-3 to inhibit the expression of IL-6R and STAT3. This finding reveals a GATA3/miR-125a-5p/IL-6R and STAT3/FOXP3 regulatory pathway, which determines how Treg cells respond to inflammatory IL-6-rich conditions.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

GATA3 Transcription Factor / metabolism
HEK293 Cells
Humans
Interleukin-6 / physiology*
Jurkat Cells
MicroRNAs / physiology*
RNA Interference
Receptors, Interleukin-6 / metabolism*
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism*
T-Lymphocytes, Regulatory / metabolism*
Up-Regulation

Substances

GATA3 Transcription Factor
GATA3 protein, human
IL6 protein, human
Interleukin-6
MIRN125 microRNA, human
MicroRNAs
Receptors, Interleukin-6
STAT3 Transcription Factor
STAT3 protein, human