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

CHAN PY; JOANNAS LD; HUNTSMAN S; WEINSTEIN JS; FLAVELL RA; BURCHARD EG; ROTHLIN CV; DE KOUCHKOVSKY D; HU D; LICONA-LIMÓN P; CRAFT JE; CORREALE J; GHOSH S; CARRERA SILVA EA; HAO L; ENG C; HERBERT DR; REPETTO SILVIA; TORGERSON DG

SCIENCE

AMER ASSOC ADVANCEMENT SCIENCE

Año: 2016 vol. 352 p. 99 - 103

0036-8075

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.