IRF2-INPP4B axis inhibits apoptosis of acute myeloid leukaemia cells via regulating T helper 1/2 cell differentiation.

Abstract

The interferon-regulatory factor 2 (IRF2)-inositol polyphosphate-4-phosphatase type-II (INPP4B) axis has been shown to suppress cell apoptosis by inducing autophagy in acute myeloid leukaemia (AML) cells. T helper type 1 cell (Th1)/Th2 imbalance is involved in development of autophagy and AML. The aim of this study was to investigate whether IRF2-INPP4B axis regulates autophagy and apoptosis of AML cells via regulating Th1/Th2 cell differentiation. The frequencies of Th2 cells and Th1 cells in transfected CD4+ T cells were determined by flow cytometry. The levels of TNF-α, IFN-γ, IL-4, and IL-13 in peripheral blood and transfected CD4+ T cells from AML patients and healthy donors were examined by ELISA assay. The mRNA levels of IRF2 and INPP4B in peripheral blood mononuclear cells (PBMCs) from AML patients and healthy donors were detected by qRT-PCR. Autophagy was evaluated by green fluorescent protein (GFP)-LC3 immunofluorescence and western blot analysis of autophagy-associated proteins. AML cell apoptosis was detected by flow cytometry. In this study, elevated frequencies of Th2 cells and reduced frequencies of Th1 cells, as well as higher expression of IRF2 and INPP4B, were observed in PBMCs from AML patients relative to healthy donors. Furthermore, IRF2 inhibited Th1 cell differentiation and promoted Th2 cell differentiation through INPP4B. Moreover, we confirmed that IRF2-INPP4B-mediated regulation of Th1/Th2 differentiation promoted autophagy and inhibited apoptosis of AML cells. Collectively, IRF2-INPP4B axis regulates autophagy and apoptosis of AML cells via regulating Th1/Th2 cell differentiation. SIGNIFICANCE OF THE STUDY: In the present study, we confirmed that IRF2-INPP4B-mediated regulation of Th1/Th2 balance promoted autophagy and inhibited apoptosis of AML cells. These findings might provide clues in better understanding of the mechanisms of AML.