 The most remarkable phenotype observed in Tyk2-deficient macrophages was lack of nitric oxide production upon stimulation with LPS.Further elucidation of molecular mechanisms of LPS signaling, showed that Tyk2 and IFN-β deficiency leads resistance to LPS-induced endotoxin shock, whereas STAT1-deficient mice are susceptible.Development of a Tyk2 inhibitor appears to be a rational approach in the drug discovery.