Using Animal Models of Celiac Disease to Understand the Role of MHC II

Abstract

Untreated CD patients develop increased numbers of intraepithelial lymphocytes, infl ammatory infi ltration of the lamina propria, intestinal permeability, and in a majority of cases, total or subtotal villous atrophy [ 1 ]. The trigger for the development of CD is gluten, typically derived from wheat, barley, and rye [ 2 ]. Gluten is a group of storage proteins found in wheat, rye, and barley. In wheat, gluten consists of two smaller subgroups of proteins, gliadins, and glutenins. In established CD patients, gliadin-specifi c T cells are more prevalent than glutenin-specifi c T cells [ 3 ]; however, there may be an initial stage of development for all CD patients in which their T cells respond to a greater number of epitopes [ 4 ]. A focusing phenomenon occurs later in which T cells in well-established CD patients are predominantly specifi c for epitopes that are a result of deamidation of gliadin by tissue transglutaminase [ 5 ]. CD is also strongly associated with HLA-DQ2 and HLA-DQ8, wherein 95 % are DQ2+ and most of the remaining are DQ8+ [ 6 ]. This contribution of MHC II is only 40 % of the familial risk, though, leaving 60 % of the genetic risk due to non-HLA genes [ 7 ]. This latter point is of great interest to the researchers that use animal models of CD for a number of reasons.The fi rst reason is that none of the spontaneous animal models seem to have a clear association with specifi c MHC II alleles, as is seen in human CD [ 8 ]. This may be interpreted in a number of ways. One interpretation is that MHC II does not play a vital role in the development of gluten-dependent enteropathy; however, years of clinical research have shown that the HLA molecules are necessary, though not suffi cient, for CD to occur [ 9 ]. Indeed, crucial information has come from T-cell lines derived from the jejunum of CD patients. Studies with these in vitro models using DQ2 and/or DQ8 restricted T cells determined that these intestinally derived T cells

Co-Silencing of Tissue Transglutaminase-2 and Interleukin-15 Genes in a Celiac Disease Mimetic Mouse Model Using a Nanoparticle-in-Microsphere Oral System

“…35,36 The poly(I:C)-based mouse model is one such system that has been used by several researchers for inducing signs and symptoms of celiac disease. 36 Poly(I:C) is a toll-like receptor-3 (TLR3) agonist that has shown to induce intestinal enteropathy similar to that observed in celiac disease. 37 In the first study that showed the effects of poly(I:C) on intestinal histopathology by Garside et al, 38 (CBAXBALB/c) F1 mice were injected intraperitoneally with poly (I:C), which resulted in a significant villous atrophy and crypt hyperplasia within 1 day post injection and recovery by 3 days post injection.…”

“…Several types of celiac disease models have been developed by researchers, which recapitulate different aspects of celiac disease. , The poly­(I:C)-based mouse model is one such system that has been used by several researchers for inducing signs and symptoms of celiac disease . Poly­(I:C) is a toll-like receptor-3 (TLR3) agonist that has shown to induce intestinal enteropathy similar to that observed in celiac disease .…”