LAUSR

Abstract Aflatoxin M1 (AFM1) is a 4-hydroxylated metabolite of aflatoxin B1 (AFB1). It induces various toxicological effects including immunotoxicity. In the present study, we investigated the effects of AFM1 on immune system and its modulation by MicroRNA (miR)-155. AFM1 was administered intraperitoneally at doses of 25 and 50 µg/kg for 28 days to Balb/c mice and different immune system parameters were analyzed. The levels of miR-155 and targeted proteins were evaluated in isolated T cells from spleens of mice. Spleen weight was reduced in mice exposed to AFM1 compared to negative control. Proliferation of splenocytes in response to phytohemagglutinin-A was reduced in mice exposed to AFM1. IFN-γ was decreased in mice exposed to AFM1, whereas IL-10 was increased. Concentration of IL-4 did not change different in mice exposed to AFM1 compared to negative control. Exposure to AFM1 reduced the expression of miR-155. Significant upregulation of phosphatidylinositol-3, 4, 5-trisphosphate 5-phosphatase 1 (Ship1) and suppressor of cytokine signaling 1 (Socs1) was observed in isolated T cells from spleens of mice treated with AFM1, but the transcription factor Maf (c-MAF) was not affected. These results suggest that miR-155 and targeted proteins might be involved in the immunotoxicity observed in mice exposed to AFM1. Graphical Abstract The Immunotoxic effects of AFM1 on T cell functions. Exposure to AFM1 reduced the expression of miR-155. Significant upregulation of Ship1 and Socs1 was observed in isolated T cells from spleens of mice treated with AFM1, but the c-MAF was not affected. Since Ship1 is a functional target of miR-155 that modulates production of IFN-γ, miR-155 may play a role in AFM1-induced Th1 response suppression (DTH) through targeting of this protein (↑ increase; ↓ decrease). Highlights AFM1 inhibited cell-mediated immunity. Exposure of mice to AFM1 resulted in a significant decrease in expression of miR-155. Exposure of mice to AFM1 resulted in up-regulation of Ship1 and Socs1.