Sensitization to and challenge with gliadin induce pancreatitis and extrapancreatic inflammation in HLA-DQ8 mice: An animal model of type 1 autoimmune pancreatitis
Gut and Liver
Autoimmune diseases; Celiac disease; Pancreatitis
Background/Aims: The aim of this study was to establish a pathogenetic mechanism of pancreatitis in celiac disease and IgG4-related disease using gluten-sensitive human leukocyte antigen (HLA)-DQ8 transgenic mice. Methods: Transgenic mice expressing HLA-DQ8 genes were utilized. Control mice were not sensitized but were fed gliadin-free rice cereal. Experimental groups consisted of gliadin-sensitized and gliadin-challenged mice; nonsensitized mice with cerulein hyperstimulation; and gliadin-sensitized and gliadinchallenged mice with cerulein hyperstimulation. Results: Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation showed significant inflammatory cell infiltrates, fibrosis and acinar atrophy compared with the control mice and the other experimental groups. The immunohistochemical analysis showed greater IgG1-positive plasma cells in the inflammatory infiltrates of gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation compared with the control mice and the other experimental groups. Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation or gliadin-sensitized and gliadinchallenged mice showed IgG1-stained inflammatory cell infiltrates in the extrapancreatic organs, including the bile ducts, salivary glands, kidneys, and lungs. Conclusions: Gliadinsensitization and cerulein hyperstimulation of gluten-sensitive HLA-DQ8 transgenic mice resulted in pancreatitis and extrapancreatic inflammation. This animal model suggests that chronic gliadin ingestion in a susceptible individual with the HLA-DQ8 molecule may be associated with pancreatitis and extrapancreatic inflammation.
Moon, S., Kim, J., Kim, M., Park, D., Song, T., Kim, S., Lee, S., Seo, D., Lee, S., & Kim, M. (2016). Sensitization to and challenge with gliadin induce pancreatitis and extrapancreatic inflammation in HLA-DQ8 mice: An animal model of type 1 autoimmune pancreatitis. Gut and Liver, 10 (5). http://dx.doi.org/10.5009/gnl15484