Mechanism and effects of Zearalenone on mouse T lymphocytes activation in vitro

Abstract

Zearalenone (ZEA) is particularly toxic to the female reproductive system. Nevertheless, the effect of ZEA on the immune system is still not fully understood. The following study investigates the effects and mechanism of ZEA on mouse T cell activation in vitro. Briefly, T lymphocytes were extracted from primary splenic lymphocyte in mice, activated by concanavalin A, and then were exposed to different concentrations of ZEA for a certain period of time. Flow cytometry was used to detect the expression of activating and co-stimulatory molecules, and the secretion of cytokines in T cells at various stages. The expression of initiation regulatory protein in T cell activation, nuclear factor protein and co-stimulatory molecule related PI3K-Akt-mTOR signaling pathway proteins were detected by western blot. Our data showed that ZEA exposure inhibits the activity of T cell, and inhibits the expression of different activation signals in T cell. Additionally, ZEA exposure reduces the expression of initiative regulatory protein, i.e. LAT, Lck, Zap-70 during the activation of T cells. Thus, the results showed that ZEA exposure inhibits the formation and transmission of activated signal in T cells, interferes with signal pathway of T cell activation nuclear factor NFAT and NFκB, and decreases the secretion of cytokines after activation. Moreover, ZEA exposure interferes with co-stimulatory molecule CD28 during T cell activation, and with the activity of the PI3K-Akt-mTOR signaling pathway downstream of CD28. To conclude, our results indicated that ZEA toxin interferes with the activation of mouse T lymphocytes by affecting TCR signal and co-stimulatory signal, thus playing an essential role in immune toxicity.

Keywords: Activation of T lymphocytes; Co-stimulatory molecule; Cytokine; Nuclear factor of T cells; TCR; Zearalenone.