MULTIPLE CELL DEATH PATHWAYS ARE ACTIVE IN THE SMALL INTESTINE. STUDIES IN CELIAC DISEASE AND A MOUSE MODEL.

CAROLINA N. RUERA; MICULÁN, EMANUEL; PEREZ, FEDERICO; DUCCA, GERÓNIMO; IRIBARREN MARÍA LUZ; GUZMAN LUCIANA; LORENA MENENDEZ; GARBI LAURA; CARASI, PAULA; CHIRDO FERNANDO

Sorrento

Simposio; 19th International Celiac Disease Symposium; 2022

International Society for the Study of Celiac Disease (ISSCD)

MULTIPLE CELL DEATH PATHWAYS ARE ACTIVE IN THE SMALL INTESTINE. STUDIES IN CELIAC DISEASE AND A MOUSE MODEL. Objective: Apoptosis is the most common cell death pathway used for massive elimination of cells. This has been considered to explain the increased lost of enterocytes in CD. However, other death mechanisms may be involved in chronic enteropathy. This study aimed to assess the role of inflammation and cell death in the small intestine in a mouse model of enteropathy and in the duodenum of celiac disease (CD) patients.Methods: Wild type mice were treated by intragastric administration of p31-43. Small intestines were collected at 4-16h after treatment. Human duodenal biopsies were collected during the procedure for CD diagnosis. Small intestine samples were used for confocal microscopy studies, western blot and RT-PCR analysis.Results: Increased number of dead cells was detected in both duodenum of untreated CD patients and in proximal small intestine of mice orally challenged with p31-43. Studies in mice showed mucosal damage and significantly increased of caspase-1, IL-1β and GSDMD active forms in p31-43 treated mice. Blocking caspase-1 and NLRP3 activity confirmed the role of the inflammasome. In human duodenal tissue, an increase in cleaved caspase-8 and -3, caspase-1, IL-1β and GSDMD in untreated CD samples was observed. Expression of RIPK3, as marker of necroptosis was also increased in tissue with enteropathy from both p31-43 treated mice and CD patients.Conclusion: Major cell death pathways (apoptosis, pyroptosis, and necroptosis) are active in the small intestine in both mice treated with p31-43 and in active CD.