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

Science (New York, N.Y.) 2016 Apr 01

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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. Copyright © 2016, American Association for the Advancement of Science.

Citation

Pamela Y Chan, Eugenio A Carrera Silva, Dimitri De Kouchkovsky, Leonel D Joannas, Liming Hao, Donglei Hu, Scott Huntsman, Celeste Eng, Paula Licona-Limón, Jason S Weinstein, De'Broski R Herbert, Joseph E Craft, Richard A Flavell, Silvia Repetto, Jorge Correale, Esteban G Burchard, Dara G Torgerson, Sourav Ghosh, Carla V Rothlin. The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity. Science (New York, N.Y.). 2016 Apr 01;352(6281):99-103