title: Iron Homeostasis and Inflammatory Status in Mice Deficient for the Cystic Fibrosis Transmembrane Regulator.
abstract: BACKGROUND
  Cystic Fibrosis (CF) is a frequent and lethal autosomal recessive disease caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Patients with CF suffer from chronic infections and severe inflammation, which lead to progressive pulmonary and gut diseases. Recently, an expanding body of evidence has suggested that iron homeostasis was abnormal in CF with, in particular, systemic iron deficiency and iron sequestration in the epithelium airway. The molecular mechanisms responsible for iron dysregulation and the relationship with inflammation in CF are unknown.
  
  
  RESULTS
  We assessed the impact of CFTR deficiency on systemic and tissue iron homeostasis as well as inflammation in wildtype and CFTR knockout (KO) mice. First, in contrast to the systemic and intestinal inflammation we observed in the CFTR KO mice, we reported the absence of lung phenotype with regards to both inflammation and iron status. Second, we showed a significant decrease of plasma ferritin levels in the KO mice, as in CF patients, likely caused by a decrease in spleen ferritin levels. However, we measured unchanged plasma iron levels in the KO mice that may be explained by increased intestinal iron absorption.
  
  
  CONCLUSIONS
  These results indicate that in CF, the lung do not predominantly contributes to the systemic ferritin deficiency and we propose the spleen as the major organ responsible for hypoferritinemia in the KO mouse. These results should provide a better understanding of iron dysregulation in CF patients where treating or not iron deficiency remains a challenging question.
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Deschemin
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Allouche
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Gif-sur-Yvette, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Brouillard
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Vaulont
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D004386:Duodenum / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018181:Mice, Inbred CFTR; D018345:Mice, Knockout; D020545:Respiratory Mucosa / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D007501:Iron