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^*

^*Corresponding author for this work

Research output: Journal article (peer-reviewed) › Journal article

19 Citations (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.

Original language	English
Pages (from-to)	519-529
Number of pages	11
Journal	Transgenic Research
Volume	23
Issue number	3
DOIs	https://doi.org/10.1007/s11248-014-9795-y
Publication status	Published - Jun 2014
Externally published	Yes

Keywords

Conditional knockout
JAK
Janus kinase
MC38
MCMV
Tumor transplant
Tyrosine kinase 2

ASJC Scopus subject areas

Biotechnology
Animal Science and Zoology
Agronomy and Crop Science
Genetics

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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.",

keywords = "Conditional knockout, JAK, Janus kinase, MC38, MCMV, Tumor transplant, Tyrosine kinase 2",

author = "Vielnascher, {Raimund M.} and Eva Hainzl and Leitner, {Nicole R.} and Michael Rammerstorfer and David Popp and Agnieszka Witalisz and Rita Rom and Marina Karaghiosoff and Thomas Kolbe and Simone M{\"u}ller and Thomas R{\"u}licke and Caroline Lassnig and Birgit Strobl and Mathias M{\"u}ller",

year = "2014",

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

language = "English",

volume = "23",

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T1 - Conditional ablation of TYK2 in immunity to viral infection and tumor surveillance

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

PY - 2014/6

Y1 - 2014/6

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

KW - Tumor transplant

KW - Tyrosine kinase 2

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DO - 10.1007/s11248-014-9795-y

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AN - SCOPUS:84899974345

SN - 0962-8819

VL - 23

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EP - 529

JO - Transgenic Research

JF - Transgenic Research

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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