Epithelial IgG and its relationship to the loss of F508 in the common mutant form of the cystic fibrosis transmembrane conductance regulator

FEBS Lett. 2009 Aug 6;583(15):2493-9. doi: 10.1016/j.febslet.2009.07.002. Epub 2009 Jul 9.

Abstract

The most debilitating feature of cystic fibrosis (CF) disease is uncontrolled inflammation of respiratory epithelium. The relationship between the commonest mutated form of CFTR (F508del or DeltaF508) and inflammation has not yet been elucidated. Here, we present a new paradigm suggesting that CFTR can interact with intra-epithelial IgG, establishing a direct link between normal CFTR and the immune system. Further, our data show that the amino-acid sequence local to F508 can bind IgG with high affinity, dependent on F508, such that loss of F508 abolishes this link both in vitro and in the intact cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cystic Fibrosis / immunology
  • Cystic Fibrosis / pathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology*
  • Epithelial Cells / physiology*
  • Humans
  • Immunoglobulin G / metabolism*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mutation*
  • Peptides / genetics
  • Peptides / metabolism
  • Phenylalanine / metabolism
  • Poxviridae / genetics
  • Poxviridae / metabolism
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / pathology
  • Sequence Alignment
  • Sheep

Substances

  • Immunoglobulin G
  • Peptides
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Phenylalanine