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

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

doi:10.1007/s11248-014-9795-y

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

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^*

^*Korrespondierende:r Autor:in für diese Arbeit

Publikation: Beitrag in Fachzeitschrift (peer-reviewed) › Artikel in Fachzeitschrift

20 Zitate (Scopus)

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.

Originalsprache	Englisch
Seiten (von - bis)	519-529
Seitenumfang	11
Fachzeitschrift	Transgenic Research
Jahrgang	23
Ausgabenummer	3
DOIs	https://doi.org/10.1007/s11248-014-9795-y
Publikationsstatus	Veröffentlicht - Juni 2014
Extern publiziert	Ja

ASJC Scopus Sachgebiete

Biotechnologie
Nutztierwissenschaften und Zoologie
Agronomie und Nutzpflanzenwissenschaften
Genetik

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title = "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.",

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doi = "10.1007/s11248-014-9795-y",

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AU - Vielnascher, Raimund M.

AU - Hainzl, Eva

AU - Leitner, Nicole R.

AU - Rammerstorfer, Michael

AU - Popp, David

AU - Witalisz, Agnieszka

AU - Rom, Rita

AU - Karaghiosoff, Marina

AU - Kolbe, Thomas

AU - Müller, Simone

AU - Rülicke, Thomas

AU - Lassnig, Caroline

AU - Strobl, Birgit

AU - Müller, Mathias

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N2 - 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.

AB - 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.

KW - Conditional knockout

KW - JAK

KW - Janus kinase

KW - MC38

KW - MCMV

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KW - Tyrosine kinase 2

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DO - 10.1007/s11248-014-9795-y

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

Abstract

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