AB051. Regulation of IL-2 production through ERK/NFATc3 signalling pathway by A20 in dendritic cells

Abstract: Dendritic cells (DCs) are the most potent antigen-presenting cells regulating naive T cell responses in vivo. A20 is negative regulator of NF-кB activation and inflammation in DCs, key players in the regulation of innate and adaptive immunity. The present study explored whether the effects of A20 on IL-2 production through ERK/NFATc3 activation in DCs. To this end, the mouse bone marrow cells are isolated and cultured with GM-CSF to attain BMDCs. The expression of co-stimulatory and signalling molecules and cell death were examined by flow cytometry, quantitative PCR and western blotting. Cytokine production was determined by ELISA methods. As a result, LPS stimulated to the increase in expression of MHC class II and CD40 as well as activation of NF-κB, STAT-1 and ERK-NFATc3 pathways, which resulted in elevated productions of IL-2, IL-12, and TNF, the effects were further enhanced in A20-deficient DCs. Targeted inhibition of ERK in A20-deficient DCs abolished the increased production of IL-2, the cytokine induced from the activation of NFATc3 in DCs. In addition, cytokine-induced cell apoptosis was unaffected by A20. In conclusion, A20 restricted cytokine production in BMDCs by inhibiting NF-κB, ERK and NFATc3 pathways.

Keywords: Dendritic cells (DCs); A20; IL-2; NF-κB; ERK; NFATc3