Grant: Operating Grant

Severe asthma is a disease with significant mortality, morbidity and pharmacoeconomic impact. Severe asthma is an inflammatory disease and is often associated with allergies and very high levels of IgE, the primary allergy antibody. Lung biopsies from severe asthmatics often have significant antibody forming cells known as B-lymphocyte in their lungs which is not found in to the same extent in milder asthmatics. Semaphorin 4C (Sema4C) is a member of a family of molecules which play an important role in development of the nervous system and blood vessels, and recently has been found to be important in regulation of the immune system. Our laboratory has found that Sema4C is highly expressed on human and murine B-lymphocytes in allergic inflammation. Moreover, mice who have had the Semaphorin 4C gene removed (Sema4C Knock-out mice) have severe bronchospasm, exceedingly high levels of IgE and increased B-lymphocytes in their lungs, all signs of severe asthma. Moreover, severe asthmatics from the McGill Severe asthma program have much lower Sema4C in their airways than mild asthmatics. In this proposal my laboratory will determine how Semaphorin 4C regulates B-lymphocytes in allergic and asthmatic pathology and thus understand a potential new direction for the therapy of severe asthma.