GM-CSF-induced autoimmune gastritis in interferon alpha receptor deficient mice

J Autoimmun. 2008 Nov;31(3):274-80. doi: 10.1016/j.jaut.2008.04.003. Epub 2008 May 23.

Abstract

Experimental autoimmune gastritis (EAG), a mouse model of human autoimmune gastritis, is characterised by gastric mononuclear cell infiltrates and parietal and zymogenic cell destruction. The gastritis is accompanied by circulating auto-antibodies to parietal cell-associated gastric H(+)/K(+) ATPase. As interferon alpha has been implicated in the regulation of immune responses, we asked whether EAG induced by the local transgenic expression of granulocyte-macrophage colony stimulating factor (GM-CSF) in the stomach (PC-GMCSF transgenic mice) would be affected by deficiency of its binding receptor. To address this, we crossed PC-GMCSF transgenic mice with mice deficient in interferon alpha (IFNalpha) receptor2 (IFNAR2). We found that EAG development in the PC-GMCSF transgenic mice was not affected by IFNAR2 deficiency. There was no difference in severity of gastric pathology, nor in autoantibody levels in the IFNAR2 deficient mice compared to wild-type, and heterozygous littermates. We conclude that the local transgenic expression of GM-CSF in the stomach overrides any possible modulatory effects of IFNAR2 on EAG development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / immunology
  • Adenosine Triphosphatases / metabolism
  • Animals
  • Autoantibodies / blood
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Disease Models, Animal
  • Gastritis / genetics
  • Gastritis / immunology*
  • Gastritis / pathology
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Mice
  • Mice, Transgenic
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / immunology
  • Receptor, Interferon alpha-beta / metabolism

Substances

  • Autoantibodies
  • Ifnar2 protein, mouse
  • Receptor, Interferon alpha-beta
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Adenosine Triphosphatases