Nothing to Sneeze At: Receptor That Puts The Breaks on Allergic Response Identified

Up to 40% of the world’s population has allergic rhinitis, commonly known as an allergy. A Yale-led study has identified an important receptor protein that regulates the intensity of the immune response to allergens. Their finding, published in Science, provides a new target for treating this pervasive health problem.

Researchers have known for years that the immune system has a built-in mechanism to regulate the intensity and duration of its response to an invader, such as dust mites. But the mechanism was poorly understood. The Yale team focused its study on a family of receptor proteins in cells that can impede the immune system response. They conducted a series of experiments on mice models, exposing them to dust mites as well as parasites, which trigger a similar immune system reaction. They confirmed that one particular receptor, TYRO3, regulated the strength of the immune response.

Image shows a woman sneezing.
The finding points to a new approach for treating allergies and possibly asthma. Image is for illustrative purposes only.

The finding points to a new approach for treating allergies and possibly asthma. “We identified a receptor, TYRO3, that puts a brake on this response,” said Dr. Carla Rothlin, senior author and associate professor of immunobiology and pharmacology. “The relevance is if you know that you have a mechanism that inhibits the response to allergens, and it’s a receptor, you can take a pharmacological approach to push this brake.” Drugs could be developed to limit the immune response in allergies, or enhance it to fight parasites, Rothlin explained.

The researchers also uncovered variants of the TYRO3 gene that are associated with another common condition: asthma. “Future studies might reveal whether it’s contributing to this disease,” said Rothlin.

About this neuroscience research

Pamela Chan, a former graduate student in Rothlin’s lab, is first author.

Source: Ziba Kashef – Yale
Image Credit: The image is in the public domain.
Original Research: Abstract for “The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity” by Pamela Y. Chan, Eugenio A. Carrera Silva, Dimitri De Kouchkovsky, Leonel D. Joannas, Liming Hao3Donglei 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. Torgerson4, Sourav Ghosh, and Carla V. Rothlin in Science. Published online April 1 2016 doi:10.1126/science.aaf1358


Abstract

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

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.

“The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity” by Pamela Y. Chan, Eugenio A. Carrera Silva, Dimitri De Kouchkovsky, Leonel D. Joannas, Liming Hao3Donglei 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. Torgerson4, Sourav Ghosh, and Carla V. Rothlin in Science. Published online April 1 2016 doi:10.1126/science.aaf1358

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