Tyrosine kinase 2 promotes sepsis-associated lethality by facilitating production of interleukin-27.

ABSTRACT: The aim of this study was to test the hypothesis that gene expression and release of IL-27 may be modulated by Tyk2. Macrophages derived from the peritoneum or bone marrow of C57BL/10SnJ (WT) mice produced abundant amounts of IL-27(p28) following TLR4 activation by LPS. In contrast, production of IL-27(p28), but not EBI3, was reduced by ∼50% in TLR4-activated macrophages derived from mice with genetic deficiency of Tyk2 compared with WT macrophages. Frequencies of IL-27(p28)+F4/80+CD11b+ cells were lower in TLR4-activated macrophages derived from Tyk2-/- mice. Mechanistically, Tyk2-/- resulted in disruption of a type I IFN-dependent mechanism for production of IL-27(p28), which was induced by type I IFNs, and release of IL-27 was defective in macrophages from IFN-β-/- and IFNAR1-/- mice. I

SUBMITTER: Bosmann M 

PROVIDER: S-EPMC4056273 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature