Tristetraprolin down-regulates IL-17 through mRNA destabilization.

An excess of interleukin 17 (IL-17) may contribute to chronic inflammatory disorders, but mechanisms that regulate IL-17 in immune cells are unclear. Here we report that tristetraprolin (TTP) inhibits IL-17 production in human T cell lines. Overexpression of TTP decreased the expression of IL-17. Conversely, TTP inhibition by siRNA increased IL-17 production. IL-17 mRNA contains eight AREs within its 3′UTR. TTP bound directly to the IL-17 mRNA 3′UTR at a location between the fourth and seventh AREs and enhanced decay of IL-17 transcripts. These results suggest that TTP could control IL-17-mediated inflammation.