Julie Ledford, PhD - an Assistant Professor in CMM - together with colleagues in the Department of Medicine and the Asthma and Airways Disease Research Center recently published their study entitled “Club Cell Secretory Protein Deficiency Leads to Altered Lung Function” in the American Journal of Respiratory and Critical Care Medicine. While Club Cell Secretory Protein 16 (CC16) has been described as a serum biomarker for obstructive lung diseases, a distinct mechanism of action for CC16 has remained elusive. This translational study used data from the birth cohort of the Tucson Children’s Respiratory Study (TCRS) and examined the relation of circulating CC16 levels with pulmonary function and responses to bronchial methacholine challenge from childhood up to age 32 years. In parallel, the study set out to comprehensively examine pulmonary physiology in mice sufficient or deficient in CC16. It was discovered in both mouse and man that deficits in CC16 significantly impaired lung function and increased sensitivity to methacholine. In addition, CC16 deficient mice had increased collagen deposition, smooth muscle thickness and elevated gene expression of factors associated with lung remodeling. Findings in mice support the clinical observations that decreased CC16 levels in serum correlate with worse lung function by providing the first line of direct evidence that lack of CC16 in the lung results in dramatically altered pulmonary function and structural alterations consistent with enhanced remodeling. PMID: 30543455
