K. Shimoda et al., Tyk2 plays a restricted role in IFN alpha signaling, although it is required for IL-12-mediated T cell function, IMMUNITY, 13(4), 2000, pp. 561-571
Janus kinases (Jaks) play an important role in signal transduction via cyto
kine receptors. Tyk2 is a Janus kinase, and we developed tyk2-deficient mic
e to study the requirement for tyk2 in vivo. Tyk2-deficient mice show no ov
ert developmental abnormalities; however, they display a lack of responsive
ness to a small amount of IFN alpha, although a high concentration of IFN a
lpha can fully transduce its signal even in the absence of tyk2. Furthermor
e, IL-12-induced T cell function is defective in these mice. In contrast, t
hese mice respond normally to IL-6 and IL-10, both of which activate tyk2 i
n vitro. These observations demonstrate that tyk2 plays only a restricted r
ole in mediating IFN alpha -dependent signaling while being required in med
iating IL-12-dependent biological responses.