Forkhead-box transcription factor 1 affects the apoptosis of natural regulatory T cells by controlling Aven expression

BMC Immunol. 2017 Mar 10;18(1):16. doi: 10.1186/s12865-017-0198-8.

Abstract

Background: Regulatory T (Treg) cells play important roles in autoimmune diseases, cancer, and organ transplantation. Forkhead box protein o1 (Foxo1) and IL-7Rα(CD127) are closely related to the homeostasis of Treg cells. However, the mechanism underlying Treg proliferation and activation remains unclear. Here, we evaluated how the over-expression of Foxo1 affects Treg cell proliferation via intracellular signaling. nTreg cells were transfected separately with Foxo1 and Aven small-interfering RNA (siRNA) or over-expression plasmid. The expression of signaling pathway genes and CD127 was confirmed using RT-qPCR and western blot analysis. The expression of cell surface molecules and apoptosis was confirmed by Flow Cytometry 3-(4, 5-Dimethylthiazol-2-yl) 2,5- diphenyltetrazolium bromide for cell proliferation assays.

Results: Foxo1 strengthened the proliferative ability of Treg cells by activating IL-7/CD127 signaling. In addition, Foxo1 suppressed Treg cell apoptosis by regulating Aven expression.

Conclusions: The results in this study indicated that Foxo1 is a positive regulatory factor for the proliferation and activity of Treg cells. Foxo1 might be a potential target for the activation of nTreg cells in vivo and in vitro.

Keywords: Apoptosis; Aven; Foxo1; Treg cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Cell Proliferation
  • Cells, Cultured
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism*
  • Gene Expression Regulation
  • Homeostasis
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Apoptosis Regulatory Proteins
  • Aven protein, mouse
  • Forkhead Box Protein O1
  • Foxo1 protein, mouse
  • Interleukin-7 Receptor alpha Subunit
  • RNA, Small Interfering