The role of invariant NKT cells in cystic fibrosis

• Applicant: Professor Dr. Gerd Döring (†)
• Subject Area: Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 42103084

• Final Report Year: 2011

Final Report Abstract

Here we demonstrate that iNKT cells accumulate in various organs of two cystic fibrosis (CF) mouse strains. iNKT cell accumulation in CF mice was independent of microbial infection. The combined analysis of CF mice and CF mice lacking iNKT cells demonstrated that iNKT cells limit the activation of autoreactive CD1d-positive B cells in CF mice presumably directed against apoptotic cell autoantigens, present in elevated rates in CF mice and in CF patients. The findings that CF patients reveal serum autoantibodies suggest that the iNKT cell control of autoreactive B cells in CF patients is not complete. Our results demonstrate a novel pathophysiological autoimmune mechanism which link iNKT cell activity to abnormal apoptosis in a mouse model of CF.

Publications

• Ceramide accumulation medi ates inflammation, cell death and infection susceptibility in cystic fibrosis. Nature Med 2008;14: 382-91
  Teichgräber V, Ulrich M, Riethmüller J, Grassme H, Wilker B, De Oliveira- Munding CC, van Heeckeren AM, Barr M, von Kürthy G, Schmid KW, Weller M, Tümmler B, Lang F, Döring G, Gulbins E