An unconventional T cell nexus drives HCK-mediated chronic obstructive pulmonary disease in mice

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory lung disease leading to progressive, destructive lung function decline, disability and death, and it is refractory to all current treatments. Haematopoietic cell kinase (HCK) is a druggable SRC-family non-receptor protein tyrosine kinase and COPD candidate gene. It is implicated in the chronic and non-resolving inflammation that causes mucosecretory bronchitis and destruction of small airways and alveoli, but how it drives pathophysiology remains obscure. Methods: Studies primarily utilised gene-targeted mice with a gain-of-function mutation in Hck that rendered the enzyme constitutively active. Bone mar..