Why do most foods not cause allergies?

in great shape , Artist’s rendering of a T cell.

One of the primary jobs of the adaptive immune system is to recognize foreign substances in our bodies and reject them without any formality by removing inflammation. So the fact that it lets about 100 grams of assorted exotic animal and plant proteins pass through our digestive systems each day is curious to take a peek at – food allergies are an exception.

The most common explanation for this “oral tolerance” is that immune cells that react to proteins in food are produced, but preferentially killed or somehow inactivated. But most of the experiments that lead to this conclusion were done with transgenic mice that had a severely impaired T cell repertoire and thus lacked a normal immune response. The new work, published in Nature, uses mice with normal, functioning immune systems to re-examine this result.

The mice were reared on a gluten-free diet and then challenged with a portion of a gluten protein called gliadin – a protein known to elicit a T cell response.

(Gliadin is half of the gluten that induces celiac disease; it promotes the generation of antibodies that react to a native protein in our guts that resembles gliadin. Gluten sensitivity and intolerance to gliadin as well as other proteins and saccharides. In wheat. Allergies in wheat are caused by gliadin and other proteins, but allergy is mediated through a different arm of the immune system.)

A week after the mice started eating the gliadin peptide, their guts showed a slight increase in T cells that responded to it. Some of these T cells may indicate a weak antibody response, but there were many regulatory T cells (Treg cells), which are immunosuppressive. Others seemed to be part of a population distinct from any well-understood T cell lineage, but could convert to Treg cells. None of these T cells could stimulate inflammation. A similar response was observed when mice were fed some other fragment of the foreign protein.

The authors suggest that under normal conditions, food-responsive T cells differentiate this poorly defined “lineage-negative” pathway based on local immunosuppressive signals in the gut and, therefore, do not trigger pathology in response to food.

So why do food allergies happen at all? The researchers speculate that, if inflammation is already present when you first eat something, over-activated T cells may develop and cause pathology.

Nature2022. DOI: 10.1038/s41586-022-04916-6

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