Endocytotic processes in celiac disease

• Applicant: Privatdozent Dr. Michael Schumann
• Subject Area: Gastroenterology ; Nutritional Sciences
• Term: from 2008 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 92218811

Celiac disease (CD) is a chronic inflammatory enteropathy with a prevalence of up to 1% in Europe. After ingestion of gliadins, a protein ingredient of common grains, the adaptive and innate immune systems are activated in predisposed individuals resulting in severe flattening of the duodenal mucosa and malabsorption. Recent research revealed that CD predisposition is not only related to genes involved in Immunologie gliadin presentation (i.e. HLA-DQ2/s) but also to genes that are crucial for the epithelial barrier and intracellular processes depending on motor proteins. In accordance with these findings a French group around Dr. M. Heyman and our group have independently shown that epithelial translocation of gliadin fragments, i.e. the initial step in triggering CD, occurs via transcytosis involving the transferrin receptor CD71 and rab5 and that changes to this process are observed in CD patients. Identification of the underlying mechanisms will enable the development of therapeutic intervention strategies in the future. For this purpose, Dr. Heyman s and our research group apply in a collaborative manner for grants. While Dr. Heyman s work will focus on a CD mouse model overexpressing CD71 which bind gliadin-lgA complexes in transcytosis, we will examine endocytotic processes important for the epithelial barrier in CD. This will include (a) the characterization of transcytotic pathways of epithelial gliadin uptake under inflammatory conditions (b) the role of endocytosis of tight junction (TJ) proteins for the integrity of the epithelial barrier in CD and (c) the quantification of the transcellular and paracellular components of epithelial gliadin uptake in relation to celiac disease activity.

• DFG Programme: Research Grants
• International Connection: France
• Participating Persons: Martine Heyman, Ph.D.; Professor Dr. Jörg-Dieter Schulzke