Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock
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- 7 April 2003
- journal article
- research article
- Published by Springer Nature in Nature Immunology
- Vol. 4 (5) , 471-477
- https://doi.org/10.1038/ni910
Abstract
Toll-like receptor-4 activation by lipopolysaccharide (LPS) induces the expression of interferon-β (IFN-β) 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-β and IFN-α4 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-β–null but not STAT1-null mice were also resistant to high dose LPS treatment. Together, these data suggest that Tyk2 and IFN-β are essential effectors in LPS induced lethality.Keywords
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