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.
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, United States.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Schmid
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, United States.
authors.forename: Iris K
authors.initials: IK
authors.lastname: Pang
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, United States.
authors.forename: Eugenio A
authors.initials: EA
authors.lastname: Carrera Silva
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, United States.
authors.forename: Lidia
authors.initials: L
authors.lastname: Bosurgi
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, United States.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Miner
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St Louis, United States.|Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States.|The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, United States.|Howard Hughes Medical Institute, Yale University, New Haven, United States.
authors.forename: Akiko
authors.identifier: 0000-0002-7824-9856
authors.initials: A
authors.lastname: Iwasaki
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, United States.
authors.forename: Carla V
authors.identifier: 0000-0002-5693-5572
authors.initials: CV
authors.lastname: Rothlin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D009980:Influenza A virus / Q000276:immunology*; D007370:Interferon Type I / Q000378:metabolism; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D014901:West Nile Fever / Q000276:immunology; D014902:West Nile virus / Q000276:immunology*; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D007370:Interferon Type I; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase
keywords: AXL RTK; IL-1β; West Nile virus; dendritic cell; immunology; influenza A virus; mouse; type I interferons; virus