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Selected Publication:

Publication type: Journal Article
Document type: Full Paper

Year: 2000

Author(s): Karaghiosoff, M; Neubauer, H; Lassnig, C; Kovarik, P; Schindler, H; Pircher, H; McCoy, B; Bogdan, C; Decker, T; Brem, G; Pfeffer, K; Müller, M

Title: Partial impairment of cytokine responses in Tyk2-deficient mice.

Source: Immunity. 2000; 13(4):549-560



Authors Vetmeduni Vienna:

Brem Gottfried
Karaghiosoff Marina
Lassnig Caroline
Müller Mathias

Vetmed Research Units
Institute of Animal Breeding and Genetics


Abstract:
To assess the role of the Janus kinase (Jak) family member Tyk2, we have generated Tyk2-/- mice. In contrast to other Jaks, where inactivation leads to a complete loss of the respective cytokine receptor signal, Tyk2-/- mice display reduced responses to IFNalpha/beta and IL-12 and a selective deficiency in Stat3 activation in these pathways. Unexpectedly, IFNgamma signaling is also impaired in Tyk2-/- mice. Tyk2-/- macrophages fail to produce nitric oxide upon lipopolysaccharide induction. Tyk2-/- mice are unable to clear vaccinia virus and show a reduced T cell response after LCMV challenge. These data imply a selective contribution of Tyk2 to the signals triggered by various biological stimuli and cytokine receptors.

Keywords Pubmed: Animals
Cell Line
Cells, Cultured
Colony-Forming Units Assay
Cytokines/biosynthesis*
Cytokines/deficiency
Cytokines/genetics
DNA-Binding Proteins/antagonists & inhibitors
DNA-Binding Proteins/deficiency
DNA-Binding Proteins/metabolism
Down-Regulation/genetics
Down-Regulation/immunology
Embryo, Mammalian
Fibroblasts
Genetic Predisposition to Disease
Granulocyte Colony-Stimulating Factor/pharmacology
Growth Inhibitors*
Humans
Interferon Type I/metabolism
Interferon Type I/pharmacology
Interferon-gamma/metabolism
Interleukin-10/pharmacology
Interleukin-12/pharmacology
Interleukin-3/pharmacology
Interleukin-6/pharmacology
Leukemia Inhibitory Factor
Leukemia Inhibitory Factor Receptor alpha Subunit
Lipopolysaccharides/pharmacology
Lymphocyte Activation/genetics
Lymphocytic Choriomeningitis/genetics
Lymphocytic Choriomeningitis/immunology
Lymphokines*
Macrophages/immunology
Macrophages/metabolism
Membrane Proteins
Mice
Mice, Inbred Strains
Myeloid Progenitor Cells/cytology
Nitric Oxide/biosynthesis
Protein-Tyrosine Kinases/deficiency*
Protein-Tyrosine Kinases/genetics*
Protein-Tyrosine Kinases/physiology
Proteins/genetics*
Proteins/physiology
Receptor, Interferon alpha-beta
Receptors, Cytokine/physiology
Receptors, Interferon/antagonists & inhibitors
Receptors, Interferon/physiology
Receptors, OSM-LIF
Rhabdoviridae Infections/genetics
Rhabdoviridae Infections/immunology
STAT3 Transcription Factor
Signal Transduction/genetics
Signal Transduction/immunology
Spleen/cytology
Spleen/enzymology
Spleen/immunology
TYK2 Kinase
Thrombopoietin/pharmacology
Trans-Activators/antagonists & inhibitors
Trans-Activators/deficiency
Trans-Activators/metabolism
Vaccinia/genetics
Vaccinia/immunology
Vesicular stomatitis Indiana virus/immunology


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