Asthma is one of the most common inflammatory diseases affecting the airways. Approximately 300 million individuals suffer from
asthma around the world. Allergic immune responses in the asthmatic airways are predominantly driven by Th2 cells and eosinophils. Lymphocyte-specific
protein tyrosine kinase (LCK) is a non-
receptor tyrosine kinase which regulates several key intracellular events through phosphorylation of its substrates. Some of the intracellular signaling pathways activated by LCK phosphorylation help in differentiation of Th2 cells which secrete allergic
cytokines that amplify airway
inflammation. Therefore, this investigative study was designed to determine the role of LCK in a cockroach extract (CE)-induced airway
inflammation murine model of allergic
asthma. Further, the effect of a pharmacological LCK inhibitor,
A-770041, on allergic airway
inflammation and key intracellular pathways in CD4+ T cells was assessed. Our data exhibit that there is an activation of LCK during allergic airway
inflammation as depicted by increased p-LCK levels in CD4+ T cells. Activated LCK is involved in the activation of ITK, PLC-γ, GATA3, NFkB, and NFATc1. Activated LCK is also involved in the upregulation of Th2 related
cytokines, such as IL-4/IL-5/
IL-13 and oxidative stress, and the downregulation of Treg cells. Furthermore, utilization of LCK inhibitor causes the reduction in p-LCK, PLC-γ, GATA3, and NFATc1 as well as Th2
cytokines and oxidative stress. LCK inhibitor causes upregulation of Treg cells in allergic mice. LCK inhibitor also caused a reduction in CE-induced airway
inflammation and mucus secretion. Therefore, the inhibition of LCK signaling could be a fruitful approach to adjust allergic airway
inflammation through the attuning of Th2/Treg immune responses. This study could lead to the design of newer treatment options for better management of allergic
inflammation in
asthma.