This IL-36/TLR4 cross-talk can explain the findings from a recent report that shows that targeting and inhibition of TLR4 prevents development of autoinflammatory symptoms in a mouse model of pustular psoriasis caused by deficiency of the IL-36 receptor antagonist (59), but mutations in the IL-36 receptor antagonist have been shown to predispose to generalized pustular psoriasis (60, 61). The gene discussed is IL1RL2; the disease is pustular psoriasis.