Antigen-specific downregulation of miR-150 in CD4 T cells promotes cell survival

Abstract

MicroRNA-150 (miR-150) has been shown to play a general role in the immune system, but very little is known about its role on CD4⁺ T cell responses. During T cell responses against superantigen Staphylococcal Enterotoxin A, miR-150 expression was down-regulated in antigen-specific CD4⁺ T cells but up-regulated in CD8⁺ T cells. CD4⁺ and CD8⁺ T cell clonal expansion was greater in miR-150-KO mice than in WT mice, but miR-150 selectively repressed IL-2 production in CD4⁺ T cells. Transcriptome analysis of CD4⁺ T cells demonstrated that apoptosis and mTOR pathways were highly enriched in the absence of miR-150. Mechanistic studies confirmed that miR-150 promoted apoptosis specifically in antigen-specific CD4⁺ T cells, but not in bystander CD4⁺ nor in CD8⁺ T cells. Furthermore, inhibition of mTOR-linked mitochondrial superoxidedismutase-2 increased apoptosis in miR-150^-/- antigen-specific CD4⁺ T. Thus, miR-150 impacts CD4⁺ T cell helper activity by attenuating IL-2 production along with clonal expansion, and suppresses superoxidedismutase to promote apoptosis.

Keywords: MiR-150; apoptosis; lymphocyte; mTOR; mitochondria; non-coding RNA; superantigen; superoxidedismutase.