title: MicroRNA-126 regulates the induction and function of CD4(+) Foxp3(+) regulatory T cells through PI3K/AKT pathway.
abstract: Recent evidence showed that limited activation of PI3K/Akt pathway was critical for induction and function sustainment of CD4(+) 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 PI3K/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 CD8(+) 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 PI3K-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 miRNAs.
authors.affiliation: Department of Immunology, Zunyi Medical College, Guizhou, 563000, China.
authors.forename: Andong
authors.initials: A
authors.lastname: Qin
authors.forename: Zhenke
authors.initials: Z
authors.lastname: Wen
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Yongju
authors.initials: Y
authors.lastname: Li
authors.forename: Junmin
authors.initials: J
authors.lastname: Luo
authors.forename: Tao
authors.initials: T
authors.lastname: Ren
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C527111:MIRN126 microRNA, human; C545201:MIRN126 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt