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

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

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

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 by Tyro3 in 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-specific Pros1 knockouts phenocopied the loss of Tyro3. Thus, a PROS1-mediated feedback from adaptive immunity engages a rheostat, TYRO3, on innate immune cells to limit the intensity of type 2 responses.

Original languageEnglish (US)
Pages (from-to)99-103
Number of pages5
JournalScience
Volume352
Issue number6281
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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