Study of in vivo effects of p31-43 gliadin peptide in a murine model of enteropathy

MARÍA GOMEZ CASTRO; CARASI PAULA; ARAYA ROMINA ELIZABETH; PEREZ FEDERICO; STRINGA PABLO; CHIRDO FERNANDO

Congreso; IV LASID Meeting LXIII Argentinean Immunology Society Meeting II French-Argentinean Immunology Meeting; 2015

Celiac Disease (CD) is a high prevalence chronic gastrointestinal disease. Villus atrophy, crypt hyperplasia, and lymphocytic infiltration are the characteristics findings in duodenal mucosa in active CD. Gluten-specific IFNproducing T cells are abundant in the mucosa. P31-43 gliadin is the most studied model peptide which has toxic effects but is not able to induce an adaptive immune response. In previous studies, we showed the toxic effects of intraluminally delivered p31-43 in a murine model of enteropathy. Receptor and signaling pathways involved in this mechanism are unknown. Our aim was to investigate the in vivo effects of p31-43 in the small intestinal mucosa. By microsurgery in C57BL6 mice, P31-43, two peptides derived from p31-43, one with inverted sequence and another with random sequence, and a not related peptide used as control, were intraluminally administrated (100 μl, 10 μg/ml). Mice were sacrificed after 4 or 16 hs post-treatment and small intestine samples were collected and histologically evaluated. MyD88 and IFNAR KO mice were assessed as well. We found that among all the peptides studied only the intraluminal administration of p31-43 induced histological changes in the small intestinal mucosa characterized by decreased Villi/Crypt ratio (p<0,001), increased intraepithelial lymphocyte number (p<0,0001) and higher histological score. Treatment of MyD88 KO and IFNαR KO mice with p31-43 did not induce histological changes.In conclusion, these results show that p31-43 induces a sequence-dependent enteropathy by innate immunity mechanisms. Intestinal damage elicited by p31-43 is MyD88 and IFNαR dependent.