Cystic Fibrosis and the Innate Immune System: Therapeutic Implications

Massimo      Conese

doi:10.2174/187153011794982022

Abstract

Cystic Fibrosis (CF), the most common autosomal lethal disorder in Caucasians, is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Although CF is multi-organ disease, the lung pathology is the chief cause of morbidity and mortality of CF patients. The hallmarks of CF lung disease are respiratory infection by opportunistic pathogens and a deranged inflammatory response. However, clinical and experimental data suggest that CF is a hyperinflammatory disorder which can arise in the absence of infection. Laboratory and animal studies suggest that CFTR is involved in regulating some neutrophil and macrophage functions and indicate that altered properties of immune cells may contribute to the dysregulated inflammation in the CF lung. Moreover, recent investigations point out to the involvement of lymphocyte subpopulations in the onset of an altered immune response to pathogens. The development of novel therapies aimed to reduce the inflammatory and regulate immune responses, including stem cell-based treatment, will be presented.

Keywords: Airway epithelial cells, cystic fibrosis (CF), CF transmembrane conductance regulator (CFTR), lymphocytes, macrophages, neutrophils, Haemophilus influenzae, Burkholderia cepacia, glutamyl-cysteinyl-glycine, sphingomyelinase, amitryptiline, transglutaminase 2, Beclin 1, neutrophil chemokines, antineutrophil elastase