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.