Open AccessMicro RNA ‐126 regulates the induction and function of CD 4 + Foxp3 + regulatory T cells through PI 3K/ AKT pathway
Author(s) -
Qin Andong,
Wen Zhenke,
Zhou Ya,
Li Ying,
Li Yongju,
Luo Junmin,
Ren Tao,
Xu Lin
Publication year - 2013
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12003
Subject(s) - gene silencing , foxp3 , pi3k/akt/mtor pathway , protein kinase b , microbiology and biotechnology , signal transduction , regulatory t cell , microrna , chemistry , biology , t cell , cancer research , immunology , immune system , il 2 receptor , biochemistry , gene
Recent evidence showed that limited activation of PI 3K/Akt pathway was critical for induction and function sustainment of CD 4 + Foxp3 + regulatory T cells (Tregs). However, the underlying mechanism remains largely unknown. In this study, we reported that miR‐126 was expressed in mouse and human Tregs. Further study showed that silencing of miR‐126 using miR‐126 antisense oligonucleotides ( ASO ) could significantly reduce the induction of Tregs in vitro . Furthermore, miR‐126 silencing could obviously reduce the expression of Foxp3 on Tregs, which was accompanied by decreased expression of CTLA ‐4 and GITR , as well as IL ‐10 and TGF ‐β, and impair its suppressive function. Mechanistic evidence showed that silencing of miR‐126 enhanced the expression of its target p85β and subsequently altered the activation of PI 3K/Akt pathway, which was ultimately responsible for reduced induction and suppressive function of Tregs. Finally, we further revealed that miR‐126 silencing could impair the suppressive function of Tregs in vivo and endow effectively antitumour effect of CD 8 + T cells in adoptive cell transfer assay using a murine breast cancer model. Therefore, our study showed that miR‐126 could act as fine‐tuner in regulation of PI 3K‐Akt pathway transduction in the induction and sustained suppressive function of Tregs and provided a novel insight into the development of therapeutic strategies for promoting T‐cell immunity by regulating Tregs through targeting specific mi RNA s.