title: The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity.
abstract: Host responses against metazoan parasites or an array of environmental substances elicit type 2 immunity. Despite its protective function, type 2 immunity also drives allergic diseases. The mechanisms that regulate the magnitude of the type 2 response remain largely unknown. Here, we show that genetic ablation of a receptor tyrosine kinase encoded byTyro3in mice or the functional neutralization of its ortholog in human dendritic cells resulted in enhanced type 2 immunity. Furthermore, the TYRO3 agonist PROS1 was induced in T cells by the quintessential type 2 cytokine, interleukin-4. T cell-specificPros1knockouts phenocopied the loss ofTyro3 Thus, a PROS1-mediated feedback from adaptive immunity engages a rheostat, TYRO3, on innate immune cells to limit the intensity of type 2 responses.
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Pamela Y
authors.initials: PY
authors.lastname: Chan
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA. Laboratorio de Trombosis Experimental, Instituto de Medicina Experimental, Academia Nacional de Medicina-CONICET, Buenos Aires, 1425, Argentina.
authors.forename: Eugenio A
authors.initials: EA
authors.lastname: Carrera Silva
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Dimitri
authors.initials: D
authors.lastname: De Kouchkovsky
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Leonel D
authors.initials: LD
authors.lastname: Joannas
authors.affiliation: Department of Pathology, School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Liming
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Medicine, University of California San Francisco, CA 94158, USA.
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Medicine, University of California San Francisco, CA 94158, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Huntsman
authors.affiliation: Department of Medicine, University of California San Francisco, CA 94158, USA.
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Licona-Limón
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Weinstein
authors.affiliation: Department of Experimental Medicine, University of California San Francisco, CA 94158, USA.
authors.forename: De'Broski R
authors.initials: DR
authors.lastname: Herbert
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA. Department of Internal Medicine (Rheumatology), School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Craft
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA. Howard Hughes Medical Institute, School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médica, University of Buenos Aires-CONICET, Buenos Aires, 1121, Argentina. Hospital de Clinicas Jose de San Martin, University of Buenos Aires, 1120, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Repetto
authors.affiliation: Center for Research on Neuroimmunological Diseases, Raúl Carrea Institute for Neurological Research (FLENI), Buenos Aires 1428, Argentina.
authors.forename: Jorge
authors.initials: J
authors.lastname: Correale
authors.affiliation: Department of Medicine, University of California San Francisco, CA 94158, USA. Department of Bioengineering, School of Pharmacy, University of California San Francisco, CA 94158, USA.
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.affiliation: Department of Medicine, University of California San Francisco, CA 94158, USA.
authors.forename: Dara G
authors.initials: DG
authors.lastname: Torgerson
authors.affiliation: Department of Neurology, School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Sourav
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA. carla.rothlin@yale.edu.
authors.forename: Carla V
authors.initials: CV
authors.lastname: Rothlin
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology*; D001798:Blood Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D006790:Host-Parasite Interactions / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000276:immunology; D017293:Protein S; D039981:Pyroglyphidae / Q000276:immunology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D017206:Strongylida Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001798:Blood Proteins; C523390:PROS1 protein, human; D017293:Protein S; D015847:Interleukin-4; D020794:Receptor Protein-Tyrosine Kinases; C084944:TYRO3 protein, human; C513478:Tyro3 protein, mouse