Ubiquitin pathway inhibitors for treatment of asthma

DESCRIPTION (provided by applicant): Asthma is a chronic disease with considerable morbidity and no cures. Symptomatic treatment is efficacious but produces significant adverse effects. Thus, improved, targeted therapies for asthma are needed. Asthma develops when T cells (CD4+) differentiate to effector T cells, which secrete cytokines that assist in the recruitment and proliferation of various innate immune cells into tissues. Th2 and Th17 cells contribute to pathogenesis by secreting inflammatory cytokines that induce the influx of neutrophils and eosinophils, leading to airway inflammation. Targeted suppression of pro-inflammatory cytokines and chemokines are thus attractive approaches to attenuate allergic responses in asthma. It is proposed here to achieve this therapeutic aim by exploiting the ubiquitin proteasome pathway. Protein ubiquitylation is a key regulatory mechanism of innate and adaptive immune systems; ligases such as Itch, Nedd4 (HECT), Cbl-b, and MID1 (RING) regulate immune responses