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

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

Author information

1
Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA.
2
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.
3
Department of Pathology, School of Medicine, Yale University, New Haven, CT 06520, USA.
4
Department of Medicine, University of California San Francisco, CA 94158, USA.
5
Department of Experimental Medicine, University of California San Francisco, CA 94158, USA.
6
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.
7
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.
8
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.
9
Center for Research on Neuroimmunological Diseases, Raúl Carrea Institute for Neurological Research (FLENI), Buenos Aires 1428, Argentina.
10
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.
11
Department of Neurology, School of Medicine, Yale University, New Haven, CT 06520, USA.
12
Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA. carla.rothlin@yale.edu.

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.

PMID:
27034374
PMCID:
PMC4935984
DOI:
10.1126/science.aaf1358
[Indexed for MEDLINE]
Free PMC Article

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