Page 996 - Veterinary Immunology, 10th Edition

macrophages, or M cells and presented to intestinal T cells in such a
VetBooks.ir way that they drive the development of IL-10–producing Treg cells.

Other tolerance-promoting molecules include retinoic acid, IDO,
and TGFβ. The microbiota appear to play a minor role in oral

tolerance since it develops in germ-free animals. If this tolerance
breaks down, a type 2 response triggered by IL-33 and ILCs may
occur. IL-33 increases mucosal permeability and promotes Th2
skewing of the immune response. In such cases, class-switching

results in the production of IgE and the development of food
allergies. Th2 responses may also occur if Tregs are destroyed or
dysfunctional.
Recent experimental evidence suggests that certain intestinal

infections may initiate food allergies by breaking oral tolerance.
Thus reoviruses can trigger Th1 responses in Peyer's patches. The
type I interferons induced by the infection then suppress pTreg
activation and so permit food allergens to trigger immune

responses. This has been demonstrated in the case of Th1 responses
to gluten but could well apply to Th2 responses as well.
About 2% of food protein is absorbed from the intestine as
peptide fragments large enough to be recognized as foreign. More

may enter if there are defects in the integrity of the enterocyte tight-
junction barrier. Antigens may enter the bloodstream and reach
skin mast cells within a few minutes. It has been estimated that up
to 30% of skin diseases in dogs are due to allergies and that

responses to food allergens may account for many cases of
cutaneous disease in dogs and cats, although their true prevalence
is unknown. The clinical consequences of food allergies are seen
both in the digestive tract and on the skin (Fig. 30.4).

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