Conditional ablation of TYK2 in immunity to viral infection and tumor surveillance.
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.
Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria.
Raimund M
RM
Vielnascher
Eva
E
Hainzl
Nicole R
NR
Leitner
Michael
M
Rammerstorfer
David
D
Popp
Agnieszka
A
Witalisz
Rita
R
Rom
Marina
M
Karaghiosoff
Thomas
T
Kolbe
Simone
S
Müller
Thomas
T
Rülicke
Caroline
C
Lassnig
Birgit
B
Strobl
Mathias
M
Müller
D000818:Animals; D051379:Mice; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000235:genetics* / Q000472:pathogenicity; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D013601:T-Lymphocytes; D053634:TYK2 Kinase / Q000096:biosynthesis / Q000235:genetics*
D053634:TYK2 Kinase; C070139:TYK2 protein, human