NEI supplementation improves alum-based immunity in CFTR KO mice

Cystic fibrosis (CF) is a genetic disorder that causes severe damage to the lungs and digestive system. CF affects the cells that produce mucus, sweat, and digestive enzymes and is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Expression and function of CFTR have been extensively studied on epithelial cells and several recent publications have shown that CFTR also regulates the functions of myeloid cells. We addressed whether CFTR is expressed by B cells and the role of CFTR in B cell functions. We found that CFTR is expressed on murine and human B cells. Compared to control wild-type (WT) mice, CFTR KO exhibited reduced frequency of B cells in lymphoid tissues and lower levels of serum immunoglobulin isotypes. Upon systemic immunization with an alum-based vaccine, CFTR KO mice developed lower antibody responses than control mice. Interestingly, vaccine supplementation with an inhibitor of the serine protease elastase (NEI) enhanced the titers of vaccine-specific serum antibody responses in CFTR KO mice and CFTR heterozygote (CFTR Het) mice. We have previously reported that NEI supplementation could promote mucosal immunity in mice immunized with the alum-based injected vaccine. In this regard, CFTR KO and CFTR Het mice immunized with NEI-supplemented alum-based injected developed higher IgA and IgG responses in saliva than control WT mice. These results provide new insights on the regulatory role of CFTR for B cell differentiation and function. They also suggest that vaccine supplementation with NEI could improve protection of individuals leaving with CF against respiratory pathogens. NIH R01 DK101323