The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity

Science. 2016 Apr 1;352(6281):99-103. doi: 10.1126/science.aaf1358.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / genetics*
  • Animals
  • Asthma / genetics
  • Asthma / immunology*
  • Blood Proteins / antagonists & inhibitors
  • Blood Proteins / genetics
  • Blood Proteins / metabolism
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Gene Knockout Techniques
  • Host-Parasite Interactions / genetics
  • Host-Parasite Interactions / immunology*
  • Humans
  • Immunity, Innate / genetics*
  • Interleukin-4 / immunology
  • Interleukin-4 / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nippostrongylus / immunology
  • Protein S
  • Pyroglyphidae / immunology
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Strongylida Infections / immunology
  • T-Lymphocytes / immunology

Substances

  • Blood Proteins
  • PROS1 protein, human
  • Protein S
  • Interleukin-4
  • Receptor Protein-Tyrosine Kinases
  • TYRO3 protein, human
  • Tyro3 protein, mouse