Elucidating the Impact of CC16 on Pulmonary Epithelial-Driven Host Responses

Club Cell Secretory Protein (CC16) is a homodimeric pneumoprotein secreted by club cells and other non-ciliated epithelial cells in the distal airways. Although the complete biological functions and mechanisms of CC16 have not been elucidated, several studies have shown that CC16 has anti-inflammatory and antioxidant properties in the lungs. Studies have shown that low circulating levels of CC16 are correlated to accelerated declines in lung function, increased inflammation, and increased disease severity in asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) patients. CC16 has also been shown to directly decrease pathogen burden, pulmonary inflammation, and airway hyperresponsiveness during a variety of bacterial and viral lung infections; thereby, further supporting its role in regulating inflammation and immune responses. The airway epithelium is the first line of defense against inhaled pathogens and environmental toxicants; therefore, making it an important mediator of inflammation and immune responses. Airway epithelial cells are important regulators of normal lung homeostasis, which includes lung fluid balance, metabolism, mucociliary clearance of trapped particulates, activation of immune cells during infection or injury, and regulation of smooth muscle function. The four major epithelial cells observed within the lungs are basal, club, ciliated, and goblet cells, all of which perform different functions within the lung. Dysregulation of epithelial cells contributes to the respiratory conditions manifested in pulmonary diseases including asthma, COPD, or CF. In these studies, we provide data showing that CC16 is important for regulating protective properties within the pulmonary epithelium during naïve conditions and during infection with Mycoplasma pneumoniae (Mp). During early life Mp infection, we show that CC16 protects the lungs by decreasing airway hyperresponsiveness, remodeling, inflammation, and Mp burden within the lung i