The IL-36 family belongs to a larger IL-1 superfamily and consists of three agonists （IL-36α/β/γ）, one antagonist （IL-36Ra）, one cognate receptor （IL-36R） and one accessory protein （IL-1RAcP）. The receptor activation follows a two-step mechanism in that the agonist first binds to IL-36R and the resulting binary complex recruits IL-1RAcP. Assembled ternary complex brings together intracellular TIR domains of receptors which activate downstream NF-κB and MAPK signaling. Antagonist IL-36Ra inhibits the signaling by binding to IL-36R and preventing recruitment of IL-1RAcP.