Immune responses are accompanied by dynamic changes in gene expression. Many transcription factors including NF-κB and AP-1 are involved in induction of genes involved in inflammatory and immune responses. However, recent studies have revealed that control of gene expression at the mRNA level is as important as transcriptional control in the immune response. We have shown that Regnase-1 encoded by the Zc3h12a gene is an endoribonuclease involved in destabilization of a variety of mRNAs including IL-6,IL-12, and Regnase-1 itself mRNAs via the stem loop structure present in the 3'UTR of these genes
Although originally identified as LPS-inducible gene, Regnase-1 protein is present in unstimulated cells, and disappears in response to Toll-like receptor ligands via an IKK-dependent proteasome degradation pathway or in response to T cell receptor stimulation through the cleavage by Malt-1. Thus, Regnase-1 acts as a brake in unstimulated cells as well as a negative feedback regulator after cellular activation. Recently we found that IL-17 signal also inhibits the function of Regnase-1. I would like to discuss the role of Regnase-1 in the immune response.