Humanized celiac-prone epithelium in vitro express MHC-II and co-stimulatory molecules necessary for gluten peptide presentation

Abstract

Background: The role intestinal epithelial cells (IECs) play in the breakdown of tolerance to gluten at an early stage in celiac disease (CeD) is unclear. Epithelial stress is a feature of CeD, and although the triggers are largely unknown, it is accompanied by expression of several markers that could be involved in initiation of inflammatory responses. IECs have been shown to express MHC class II (MHC-II) molecules and participate in antigen presentation in several models. Whether IECs can participate in gluten peptide presentation, the major environmental trigger in celiac disease, is unknown. To study this, a model expressing human MHC-II, HLA DQ8 or HLADQ2, would be required. Aims: To develop organoid monolayers from transgenic mice expressing human celiac risk genes: HLA-DQ8 and -DQ2. To investigate conditions leading to the induction of epithelial MHC-II and its main co-stimulatory molecules, CD80, CD86 and CD40, that could enable early gluten peptide presentation.