| First Author | Karaghiosoff M | Year | 2003 |
| Journal | Nat Immunol | Volume | 4 |
| Issue | 5 | Pages | 471-7 |
| PubMed ID | 12679810 | Mgi Jnum | J:83115 |
| Mgi Id | MGI:2657017 | Doi | 10.1038/ni910 |
| Citation | Karaghiosoff M, et al. (2003) Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Nat Immunol 4(5):471-7 |
| abstractText | Toll-like receptor-4 activation by lipopolysaccharide (LPS) induces the expression of interferon-beta (IFN-beta) in a MyD88-independent manner. Here we report that mice devoid of the JAK protein tyrosine kinase family member, Tyk2, were resistant to shock induced by high doses of LPS. Basal and LPS-induced expression of IFN-beta and IFN-alpha4 mRNA in Tyk2-null macrophages were diminished. However, Tyk2-null mice showed normal systemic production of nitric oxide and proinflammatory cytokines and the in vivo response to tumor necrosis factor (TNF) was unperturbed. IFN-beta-null but not STAT1-null mice were also resistant to high dose LPS treatment. Together, these data suggest that Tyk2 and IFN-beta are essential effectors in LPS induced lethality. |
