Partial impairment of cytokine responses in Tyk2-deficient mice

To assess the role of the Janus kinase (Jak) family member Tyk2, we have ge nerated Tyk2(-/-) mice. In contrast to other Jaks, where inactivation leads to a complete loss of the respective cytokine receptor signal, Tyk2(-/-) m ice display reduced responses to IFN alpha/beta and IL-12 and a selective d eficiency in Stat3 activation in these pathways. Unexpectedly, lFN gamma si gnaling is also impaired in Tyk2(-/-) mice. Tyk2(-/-) macrophages fail to p roduce nitric oxide upon lipopolysaccharide induction. Tyk2(-/-) mice are u nable to clear vaccinia virus and show a reduced T cell response after LCMV challenge. These data imply a selective contribution of Tyk2 to the signal s triggered by various biological stimuli and cytokine receptors.