GSE134900 The interplay between IL-15, gluten and HLA-DQ8 drives the development of coeliac disease in mice

Contributors : Luis Barreiro ; Bana JabriSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensCoeliac disease (CeD) is a complex, polygenic inflammatory enteropathy with autoimmune features caused by exposure to dietary gluten that occurs in a subset of genetically susceptible HLA-DQ8 and HLA-DQ2 individuals. Attempts to develop a pathophysiologically relevant animal model that develops villous atrophy (VA) have failed. The need to develop non-dietary treatments for this common disorder is now widely recognized, but it is hampered by the lack of a preclinical model. Furthermore, while human studies have led to major advances in our understanding of CeD pathogenesis, direct demonstration of the respective roles of disease-predisposing HLA molecules, and adaptive and innate immunity in the development of tissue damage is missing. To address these unmet needs, we engineered a mouse model that reproduces the dual overexpression of IL-15 in the gut epithelium and the lamina propria (Lp) characteristic of active CeD, expresses the predisposing HLA-DQ8 molecule, and develops VA upon gluten ingestion. We show that overexpression of IL-15 in both the epithelium and Lp is required for development of VA, demonstrating the location-dependent central role of IL-15 in CeD pathogenesis. Furthermore, our study reveals the critical role played by both CD4+ and cytotoxic CD8+ T cells in VA development. Finally, it establishes that HLA-DQ8 is central for tiss...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research