Widespread alterations in the peripheral blood innate immune cell profile in cystic fibrosis reflect lung pathology

Cystic fibrosis (CF) is caused by mutations to the CF transmembraneconductance regulator (CFTR) gene. CFTR is known to be expressed on multipleimmune cell subtypes, dendritic cells, monocytes/macrophages, neutrophils andlymphocytes. We hypothesized that the lack of CFTR expression on peripheralblood innate immune cells would result in an altered cell profile in the peripheryand that this profile would reflect lung pathology. We performed a flowcytometric phenotypic investigation of innate immune cell proportions inperipheral blood collected from 17 CF patients and 15 age-matched healthycontrols. We observed significant differences between CF patients and controls inthe relative proportions of natural killer (NK) cells, monocytes and their subsets,with significant correlations observed between proportions of NK and monocytecell subsets and lung function (forced expiratory volume in 1 sec, % predicted;FEV1% predicted) in CF patients. This study demonstrates the widespreadnature of immune dysregulation in CF and provides a basis for identification ofpotential therapeutic targets. Modulation of the distinct CF-related immune cellphenotype identified could also be an important biomarker for evaluating CFTRtargeted drug efficacy.