IL-36Ra belongs to IL-1 cytokine family, as a receptor antagonist. Like other IL-36 cytokines, IL-36Ra does not contain caspase cleavage sites, but removal of N-terminal methionine is required for its full activity, which might be mediated by neutrophil elastase. IL-36Ra shares sequence homology with IL-1Ra, another receptor antagonist of the IL-1 family. IL-36Ra inhibits IL-36α, IL-36β, IL-36γ signaling by preventing their binding to IL-1RL2/IL-36R and the recruitment of IL-1RAP co-receptor, leading to blockage of downstream NF-kB and MAP kinase activation. The mechanism of inhibition is similar to the one that is established between IL-1Ra and IL-1. IL-36Ra is involved in innate immunity and anti-inflammatory responses. IL-36Ra attenuates IL-36 cytokine-induced pro-inflammatory cytokine production by bone marrow derived dendritic cells and antagonizes IL-36 cytokine-induced IFN-γ, IL-4, and IL-17 production in CD4+ T cells. In addition, the anti-inflammatory effect of IL-36Ra in brain is SIGIRR/TIR8-dependent. The deficiency of IL-36Ra is linked to psoriasis in humans. The deficit of IL-36Ra exacerbates skin inflammation in IL-36α transgenic mice, suggesting the importance of IL-36Ra as anti-inflammatory cytokine. The expression of IL-36Ra is induced by PMA and LPS in THP-1 cells and by Aspergillus fumigatus in human PBMCs.