GM-CSF-induced autoimmune gastritis in interferon alpha receptor deficient mice.
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.
Field
Judith
J
Department of Medicine, Monash University, Clayton, Victoria 3168, Australia.
Alderuccio
Frank
F
Hertzog
Paul
P
Toh
Ban-Hock
BH
D000251:Adenosine Triphosphatases / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005756:Gastritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; C508034:Ifnar2 protein, mouse; D053633:Receptor, Interferon alpha-beta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000251:Adenosine Triphosphatases