The role of NFAT2/miR-20a-5p signaling pathway in the regulation of CD8+ naïve T cells activation and differentiation

Abstract

T cell dysfunction is a common characteristic in leukemia patients that significantly impacts clinical treatment and prognosis. However, the mechanism underlying T cell dysfunction and its reversal remains unclear. In this study, in accordance with our previous findings, we found that the expression of NFAT2 and pri-miR-17 ~ 92 are lower in peripheral blood CD3⁺ T cells from chronic myelogenous leukemia (CML) patients by gene expression analysis. We further demonstrate that the NFAT2-induced activation, differentiation, and expression of cytokines in human umbilical cord blood CD8⁺ naïve T cells are miR-20a-5p dependent. We also preliminarily explored the relationship between NFAT2 and miR-20a-5p in naive T cells. These results suggest that NFAT2 and miR-20a are crucial for regulating functional CD8⁺ T cells. Additionally, their alteration may be related to CD8⁺ T cell dysfunction in CML patients; thus, NFAT2 and miR-20a-5p may be considered potential targets for revising T cell function in leukemia immunotherapy.

Keywords: CD8(+) T cell; CML; Immunotherapy; NFAT2; T cell dysfunction; miR-20a-5p.