The novel role of downstream of kinase-1 in the ovalbumin-induced murine model of asthma (141.4)

Abstract

Abstract The downstream of kinase (DOK)-1, a 62 kDa adaptor protein negatively regulates the protein tyrosine kinase (PTK) pathway in mast cells, but the role of DOK-1 in a murine model of asthma has not been defined. This study provides experimental evidence demonstrating that DOK-1 is a key regulator for aiway inflammation in a murine model of asthma. Here, we have found that the markable reduction of pulmonary CD4+ T cell population and Th2 cytokines leads to the inhibition of pulmonary CD4+ T cell differentiation into Th2 cells in DOK-1 overexpression mice. DOK-1 overexpression in STAT-6 knockout (KO) mice increased the expression of STAT-4 and T-bet, which is transcription factor for Th1 differentiation. Conversely, Th2 regulatory molecules, STAT-6 and GATA-3 are impaired by DOK-1 overexpression in STAT-4 KO mice. Taken together, DOK-1 regulates Th1/Th2 immune balance through STAT4- and STAT6-dependent pathways, our findings provide additional insight into the immunological function of DOK-1 in Th2 inflammation and suggest a new potential therapeutic target for the treatment of asthmatic patients.