title: Invariant natural killer T (iNKT) cells prevent autoimmunity, but induce pulmonary inflammation in cystic fibrosis.
abstract: OBJECTIVE
  Inflammation is a major and critical component of the lung pathology in the hereditary disease cystic fibrosis. The molecular mechanisms of chronic inflammation in cystic fibrosis require definition.
  
  
  METHODS
  We used several genetic mouse models to test a role of iNKT cells and ceramide in pulmonary inflammation of cystic fibrosis mice. Inflammation was determined by the pulmonary cytokine profil and the abundance of inflammatory cells in the lung.
  
  
  RESULTS
  Here we provide a new concept how inflammation in the lung of individuals with cystic fibrosis is initiated. We show that in cystic fibrosis mice the mutation in the Cftr gene provokes a significant up-regulation of iNKT cells in the lung. Accumulation of iNKT cells serves to control autoimmune disease, which is triggered by a ceramide-mediated induction of cell death in CF organs. Autoimmunity becomes in particular overt in cystic fibrosis mice lacking iNKT cells and although suppression of the autoimmune response by iNKT cells is beneficial, IL-17(+) iNKT cells attract macrophages and neutrophils to CF lungs resulting in chronic inflammation. Genetic deletion of iNKT cells in cystic fibrosis mice prevents inflammation in CF lungs.
  
  
  CONCLUSIONS
  Our data demonstrate an important function of iNKT cells in the chronic inflammation affecting cystic fibrosis lungs. iNKT cells suppress the auto-immune response induced by ceramide-mediated death of epithelial cells in CF lungs, but also induce a chronic pulmonary inflammation.
authors: Institute of Medical Microbiology and Hygiene University Hospital, Tübingen, Germany.
authors: Nanna
authors: N
authors: Siegmann
authors: David
authors: D
authors: Worbs
authors: Frauke
authors: F
authors: Effinger
authors: Tobias
authors: T
authors: Bormann
authors: Madlen
authors: M
authors: Gebhardt
authors: Martina
authors: M
authors: Ulrich
authors: Fredrik
authors: F
authors: Wermeling
authors: Eva
authors: E
authors: Müller-Hermelink
authors: Tilo
authors: T
authors: Biedermann
authors: Mike
authors: M
authors: Tighe
authors: Michael J
authors: MJ
authors: Edwards
authors: Charles
authors: C
authors: Caldwell
authors: Elizabeth
authors: E
authors: Leadbetter
authors: Mikael C I
authors: MC
authors: Karlsson
authors: Katrin Anne
authors: KA
authors: Becker
authors: Erich
authors: E
authors: Gulbins
authors: Gerd
authors: G
authors: Döring
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018181:Mice, Inbred CFTR; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology
chemical_list: D001323:Autoantibodies; D020381:Interleukin-17; D019005:Cystic Fibrosis Transmembrane Conductance Regulator