Conditional ablation of TYK2 in immunity to viral infection and tumor surveillance.

Abstract

Tyrosine kinase 2 (TYK2) has a pivotal role in immunity to infection and tumor surveillance. It is associated with several cytokine receptor chains including type I interferon (IFN) receptor 1 (IFNAR1), interleukin- (IL-) 12 receptor beta 1 (IL-12Rb1) and IL-10R2. We have generated a mouse with a conditional Tyk2 null allele and proved integrity of the conditional Tyk2 locus. TYK2 was successfully removed by the use of ubiquitous and tissue-specific Cre-expressing mouse strains. Myeloid TYK2 was found to critically contribute to the defense against murine cytomegalovirus. Ubiquitous TYK2 ablation severely impaired tumor immunosurveillance, while deletion in myeloid, dendritic or T cells alone showed no effect. The conditional Tyk2 mouse strain will be instrumental to further dissect TYK2 functions in infection, inflammation and cancer.

• Authors: Raimund M Vielnascher, Eva Hainzl, Nicole R Leitner, Michael Rammerstorfer, David Popp, Agnieszka Witalisz, Rita Rom, Marina Karaghiosoff, Thomas Kolbe, Simone Müller, Thomas Rülicke, Caroline Lassnig, Birgit Strobl, Mathias Müller
• Journal: Transgenic research (Transgenic Res) Vol. 23 Issue 3 Pg. 519-29 (Jun 2014) ISSN: 1573-9368 [Electronic] Netherlands
• PMID: 24696087 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• TYK2 Kinase
• TYK2 protein, human

Topics

• Animals
• Mice
• Mice, Transgenic
• Muromegalovirus (genetics, pathogenicity)
• Neoplasms (genetics, pathology)
• Signal Transduction (genetics)
• T-Lymphocytes
• TYK2 Kinase (biosynthesis, genetics)