TYRO3-PROS1 axis is a novel inhibitory circuit for type II immunity

This week Science published very simple and concise study showing that in mice DC-specific TYRO3 [TAM] receptor tyrosine kinase, and T_H2 cell-specific TAM receptor agonist PROS1, represent novel inhibitory circuit dampening type II immunity (allergy, asthma, atopic dermatitis).

The senior author for this study, Carla V. Rothlin (department of immunobiology, School of Medicine, Yale University) is a shareholder of Kolltan Pharmaceuticals, so we may see some of these data going into biotech drug design. 

Using a house dust mite (HDM) model of allergic airway inflammation, the authors showed that Tyro3^–/– mice showed exaggerated allergic (T_H2) response.

Next, the authors showed that PDL2⁺ CD11c⁺ DCs expressed Tyro3 and that Tyro3^–/– PDL2⁺ DCs were the main drivers of exaggerated T_H2 cell response.

Finally, mice lacking CD4 T cell-specific PROS1 expression (Tyro3 agonist ligand) displayed similar exaggerated T_H2 cell response to the helminth N. brasiliensis ( T_H2 activator).

In summary, this study revealed that Tyro3-PROS1 axis represents novel inhibitory circuit specifically involved in regulating type II immune response (but not in T_H1 or T_H17 responses) and it could be targeted therapeutically (though it is not clear whether Tyro3-PROS1 axis also functions in humans. Limited data about human cells provided by the authors in the article were not conclusive).

David Usharauli