The role of chitinase-like proteins Ym1 and Ym2 in type 2 immunity.

Ym1 and Ym2 are chitinase-like proteins (CLPs) that are abundantly induced in the lungs of mice
with asthma and in mice with helminth infection. Very similar CLPs are found in the blood of
asthmatics, and these are used as biomarkers for asthma severity and lung function decline. Their
function is unknown.
Ym1 is best known as a highly expressed marker of alternatively activated macrophages (AAMs).
These immune cells are associated with type 2 immune responses and are involved in wound
healing, tissue repair, defense against parasites, airway remodeling and lung development. In
asthmatic airways and in helminth infection, Ym1 and Ym2 can also occur in a crystalline state, but
the functional importance of this is completely unknown.
Due to a lack of selective Ym1 and Ym2 deficient mouse models, the detailed immunological
functions of these proteins have remained elusive. We hypothesize that Ym1/Ym2 are more than
just markers of AAMs. We speculate that these CLPs contribute to the intensity and type of
immune response to the antigens and pathogens that elicit them, and are important drivers of
tissue remodeling. In the last year, we have already created unique Ym1 and Ym2 deficient mice,
and ways to produce soluble and crystalline Ym1. With these highly unique tools, we will investigate if and how the lack of Ym1 and Ym2 affects the development of pathogenic type 2
immunity in asthma, protective immunity to helminths and lung development and remodeling.