The HLA-DQ8 transgenic mouse: A model to study the immune and cytotoxic responses to wheat gliadin

Methods Cell Biol. 2023:179:157-171. doi: 10.1016/bs.mcb.2023.01.007. Epub 2023 May 16.

Abstract

A complete understanding of celiac disease (CD) pathogenesis has been hindered to date because of the lack of adequate in vivo models. Herein, we describe two in vivo approaches in HLA-DQ8-transgenic mice to study the intrinsic cytoxicity and immune features of wheat gliadin. By adopting the first method, we explored the mucosal architecture of the small intestine following the intra-gastric administration of wheat gliadin in mice treated with indomethacin, an inhibitor of cyclooxygenases. Mice showed a significant reduction of villus height, increased crypt depth and increased intraepithelial lymphocytes. The second approach involved the mucosal sensitization to gliadin via the intranasal route. This protocol induced a Th1/Th17 phenotype in mesenteric lymph nodes, as described in CD. In conclusion, these methods remain instrumental to analyze in vivo distinct biological features of wheat gliadin and related prolamins. Furthermore, the sensitization protocol could be exploited to test innovative strategies downregulating the gliadin-specific immunity.

Keywords: Cytotoxicity; HLA-DQ8 transgenic mouse; Mucosal immunity; Wheat gluten.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gliadin*
  • HLA-DQ Antigens / genetics
  • Mice
  • Mice, Transgenic
  • Triticum* / genetics

Substances

  • HLA-DQ8 antigen
  • Gliadin
  • HLA-DQ Antigens