AXL receptor tyrosine kinase is required for t cell priming and antiviral immunity

Edward T. Schmid; Iris K. Pang; Eugenio A. Carrera Silva; Lidia Bosurgi; Jonathan J. Miner; Michael S. Diamond; Akiko Iwasaki; Carla V. Rothlin

doi:10.7554/eLife.12414.001

AXL receptor tyrosine kinase is required for t cell priming and antiviral immunity

Edward T. Schmid, Iris K. Pang, Eugenio A. Carrera Silva, Lidia Bosurgi, Jonathan J. Miner, Michael S. Diamond, Akiko Iwasaki, Carla V. Rothlin

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

The receptor tyrosine kinase (RTK) AXL is induced in response to type I interferons (IFNs) and limits their production through a negative feedback loop. Enhanced production of type I IFNs in Axl^-/-dendritic cells (DCs) in vitro have led to speculation that inhibition of AXL would promote antiviral responses. Notwithstanding, type I IFNs also exert potent immunosuppressive functions. Here we demonstrate that ablation of AXL enhances the susceptibility to infection by influenza A virus and West Nile virus. The increased type I IFN response in Axl^-/-mice was associated with diminished DC maturation, reduced production of IL-1β, and defective antiviral T cell immunity. Blockade of type I IFN receptor or administration of IL-1β to Axl^-/-mice restored the antiviral adaptive response and control of infection. Our results demonstrate that AXL is essential for limiting the immunosuppressive effects of type I IFNs and enabling the induction of protective antiviral adaptive immunity.

Original language	English
Article number	e12414
Journal	eLife
Volume	5
Issue number	JUNE2016
DOIs	https://doi.org/10.7554/eLife.12414.001
State	Published - Jun 28 2016

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10.7554/eLife.12414.001

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title = "AXL receptor tyrosine kinase is required for t cell priming and antiviral immunity",

abstract = "The receptor tyrosine kinase (RTK) AXL is induced in response to type I interferons (IFNs) and limits their production through a negative feedback loop. Enhanced production of type I IFNs in Axl-/-dendritic cells (DCs) in vitro have led to speculation that inhibition of AXL would promote antiviral responses. Notwithstanding, type I IFNs also exert potent immunosuppressive functions. Here we demonstrate that ablation of AXL enhances the susceptibility to infection by influenza A virus and West Nile virus. The increased type I IFN response in Axl-/-mice was associated with diminished DC maturation, reduced production of IL-1β, and defective antiviral T cell immunity. Blockade of type I IFN receptor or administration of IL-1β to Axl-/-mice restored the antiviral adaptive response and control of infection. Our results demonstrate that AXL is essential for limiting the immunosuppressive effects of type I IFNs and enabling the induction of protective antiviral adaptive immunity.",

author = "Schmid, {Edward T.} and Pang, {Iris K.} and {Carrera Silva}, {Eugenio A.} and Lidia Bosurgi and Miner, {Jonathan J.} and Diamond, {Michael S.} and Akiko Iwasaki and Rothlin, {Carla V.}",

note = "Publisher Copyright: {\textcopyright} Schmid et al.",

year = "2016",

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doi = "10.7554/eLife.12414.001",

language = "English",

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T1 - AXL receptor tyrosine kinase is required for t cell priming and antiviral immunity

AU - Schmid, Edward T.

AU - Pang, Iris K.

AU - Carrera Silva, Eugenio A.

AU - Bosurgi, Lidia

AU - Miner, Jonathan J.

AU - Diamond, Michael S.

AU - Iwasaki, Akiko

AU - Rothlin, Carla V.

PY - 2016/6/28

Y1 - 2016/6/28

N2 - The receptor tyrosine kinase (RTK) AXL is induced in response to type I interferons (IFNs) and limits their production through a negative feedback loop. Enhanced production of type I IFNs in Axl-/-dendritic cells (DCs) in vitro have led to speculation that inhibition of AXL would promote antiviral responses. Notwithstanding, type I IFNs also exert potent immunosuppressive functions. Here we demonstrate that ablation of AXL enhances the susceptibility to infection by influenza A virus and West Nile virus. The increased type I IFN response in Axl-/-mice was associated with diminished DC maturation, reduced production of IL-1β, and defective antiviral T cell immunity. Blockade of type I IFN receptor or administration of IL-1β to Axl-/-mice restored the antiviral adaptive response and control of infection. Our results demonstrate that AXL is essential for limiting the immunosuppressive effects of type I IFNs and enabling the induction of protective antiviral adaptive immunity.

AB - The receptor tyrosine kinase (RTK) AXL is induced in response to type I interferons (IFNs) and limits their production through a negative feedback loop. Enhanced production of type I IFNs in Axl-/-dendritic cells (DCs) in vitro have led to speculation that inhibition of AXL would promote antiviral responses. Notwithstanding, type I IFNs also exert potent immunosuppressive functions. Here we demonstrate that ablation of AXL enhances the susceptibility to infection by influenza A virus and West Nile virus. The increased type I IFN response in Axl-/-mice was associated with diminished DC maturation, reduced production of IL-1β, and defective antiviral T cell immunity. Blockade of type I IFN receptor or administration of IL-1β to Axl-/-mice restored the antiviral adaptive response and control of infection. Our results demonstrate that AXL is essential for limiting the immunosuppressive effects of type I IFNs and enabling the induction of protective antiviral adaptive immunity.

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DO - 10.7554/eLife.12414.001

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SN - 2050-084X

VL - 5

JO - eLife

JF - eLife

IS - JUNE2016

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ER -

AXL receptor tyrosine kinase is required for t cell priming and antiviral immunity

Abstract

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