Evaluation of the response to elexacaftor-tezacaftor-ivacaftor of the rare CFTR variants L383S, I507del, L1065P and R1066H in intestinal organoid-derived epithelial monolayers.

Introduction: Cystic fibrosis (CF) is caused by mutation of the CFTR gene, encoding an epithelial anion channel. Here we evaluated the effect of the modulator combination elexacaftor-tezacaftor-ivacaftor (ETI) on the function of four rare, poorly characterized CFTR variants: L383S, I507del, L1065P and R1066H.

Methods: Intestinal organoids were obtained from subjects carrying the CFTR variants L383S, I507del, L1065P or R1066H in trans of a minimal function allele (class I mutation).

Pro-inflammatory cytokines stimulate CFTR-dependent anion secretion in pancreatic ductal epithelium.

Background: Loss of CFTR-dependent anion and fluid secretion in the ducts of the exocrine pancreas is thought to contribute to the development of pancreatitis, but little is known about the impact of inflammation on ductal CFTR function. Here we used adult stem cell-derived cell cultures (organoids) obtained from porcine pancreas to evaluate the effects of pro-inflammatory cytokines on CFTR function.

Methods: Organoids were cultured from porcine pancreas and used to prepare ductal epithelial monolayers.

Bicarbonate Transport in Cystic Fibrosis and Pancreatitis.

CFTR, the cystic fibrosis (CF) gene-encoded epithelial anion channel, has a prominent role in driving chloride, bicarbonate and fluid secretion in the ductal cells of the exocrine pancreas. Whereas severe mutations in cause fibrosis of the pancreas in utero, CFTR mutants with residual function, or CFTR variants with a normal chloride but defective bicarbonate permeability (CFTR), are associated with an enhanced risk of pancreatitis. Recent studies indicate that CFTR function is not only compromised in genetic but also in selected patients with an acquired form of pancreatitis induced by alcohol, bile salts or smoking.