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

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19 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 languageEnglish
Article numbere12414
JournaleLife
Volume5
Issue numberJUNE2016
DOIs
StatePublished - Jun 28 2016

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    Schmid, E. T., Pang, I. K., Carrera Silva, E. A., Bosurgi, L., Miner, J. J., Diamond, M. S., Iwasaki, A., & Rothlin, C. V. (2016). AXL receptor tyrosine kinase is required for t cell priming and antiviral immunity. eLife, 5(JUNE2016), [e12414]. https://doi.org/10.7554/eLife.12414.001