Animal models to study gluten sensitivity

Abstract

The initial development and maintenance of tolerance to dietary antigens is a complex process that, when prevented or interrupted, can lead to human disease. Understanding the mechanisms by which tolerance to specific dietary antigens is attained and maintained is crucial to our understanding of the pathogenesis of diseases related to intolerance of specific dietary antigens. Two diseases that are the result of intolerance to a dietary antigen are celiac disease (CD) and dermatitis herpetiformis (DH). Both of these diseases are dependent upon the ingestion of gluten (the protein fraction of wheat, rye, and barley) and manifest in the gastrointestinal tract and skin, respectively. These gluten-sensitive diseases are two examples of how devastating abnormal immune responses to a ubiquitous food can be. The well-recognized risk genotype for both is conferred by either of the HLA class II molecules DQ2 or DQ8. However, only a minority of individuals who carry these molecules will develop either disease. Also of interest is that the age at diagnosis can range from infancy to 70–80 years of age. This would indicate that intolerance to gluten may potentially be the result of two different phenomena. The first would be that, for various reasons, tolerance to gluten never developed in certain individuals, but that for other individuals, prior tolerance to gluten was lost at some point after childhood. Of recent interest is the concept of non-celiac gluten sensitivity, which manifests as chronic digestive or neurologic symptoms due to gluten, but through mechanisms that remain to be elucidated. This review will address how animal models of gluten-sensitive disorders have substantially contributed to a better understanding of how gluten intolerance can arise and cause disease.

Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness

“…1,21 In healthy individuals, the immune system, through innate and adaptive immunity, plays a central role in the maintenance of tolerance to dietary antigens and other potential harmful pathogens, thus protecting the organism from the development of diseases. 22 The innate immune response is immediate and fast, including both cellular and humoral components. 23 Several cells are involved, including macrophages, neutrophils, dendritic cells, monocytes, mast cells and natural killer T cells, expressing both natural killer receptors and CD1d-restricted ab-T-cell receptors.…”

Generation of food-grade recombinant Lactobacillus casei delivering Myxococcus xanthus prolyl endopeptidase

“…In vitro approaches including intestinal biopsy organ culture and cell lines were advantageous, however nowadays animal models provide much information. Different species have been used as animal model of CD including dogs, horses, monkeys, rats, rabbits and mice, even if none mimics all the features of the disease (Marietta and Murray 2012; Schuppan et al 2009; Stoven et al 2013). Gluten sensitive rhesus macaques are good for testing new therapies as the applicability of the barley endoprotease, EP-B2 (Bethune et al 2008) and new-born rats sensitised with INF-γ and fed gliadin evaluated the administration of a Bifidum strain (Laparra et al 2013).…”

A Mouse Model of Anaphylaxis and Atopic Dermatitis to Salt-Soluble Wheat Protein Extract

“…The potential utility of mouse models in basic and applied biomedical research is well appreciated [30,31,32]. Along with previous mouse models of gliadin sensitivity, our new model of SSWP hypersensitivity with additional clinical (i.e., dermatitis) and mediator (i.e., mMCP-1) phenotypes should provide a novel opportunity for further research and development.…”