Defective Inflammation Resolution in Cystic Fibrosis: Cellular Mechanisms and Emerging Pro-resolving Therapies in the CFTR Modulator Era.

Abstract

Cystic fibrosis (CF) is a fatal monogenic hereditary disease that affects approximately 100,000 people worldwide. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, impairing biosynthesis and/or function of a protein that regulates chloride and bicarbonate fluxes. CFTR loss of function is associated with aberrant, non-resolving inflammation that in combination with recurrent infection leads to respiratory insufficiency. Cellular and molecular studies have uncovered failures in key mechanisms of inflammation resolution, consequent to loss of function of CFTR expressed by leukocytes, platelets, and epithelial and endothelial cells. This chapter illustrates these processes and discusses pro-resolving therapeutic approaches to combat CF inflammation.