| First Author | Shimoda K | Year | 2002 |
| Journal | Blood | Volume | 99 |
| Issue | 6 | Pages | 2094-9 |
| PubMed ID | 11877284 | Mgi Jnum | J:115369 |
| Mgi Id | MGI:3691506 | Doi | 10.1182/blood.v99.6.2094 |
| Citation | Shimoda K, et al. (2002) Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice. Blood 99(6):2094-9 |
| abstractText | Tyk2 is activated in response to interleukin-12 (IL-12) and is essential for IL-12-induced T-cell function, including interferon-gamma (IFN-gamma) production and Th1 cell differentiation. Because IL-12 is a stimulatory factor for natural killer (NK) cell-mediated cytotoxicity, we examined whether tyk2 is required for IL-12-induced NK cell activity. IL-12-induced NK cell activity in cells from tyk2-deficient mice was drastically reduced compared to that in cells from wild-type mice. IL-18 shares its biologic functions with IL-12. However, the molecular mechanism of IL-18 signaling, which activates an IL-1 receptor-associated kinase and nuclear translocation of nuclear factor-kappaB, is different from that of IL-12. We next examined whether biologic functions induced by IL-18 are affected by the absence of tyk2. NK cell activity and IFN-gamma production induced by IL-18 were reduced by the absence of tyk2. Moreover, the synergistic effect of IL-12 and IL-18 for the production of IFN-gamma was also abrogated by the absence of tyk2. This was partially due to the absence of any up-regulation of the IL-18 receptor treated with IL-12, and it might suggest the presence of the cross-talk between Jak-Stat and mitogen-activated protein kinase pathways in cytokine signaling. |
