Food Allergy

A Glimpse Into the Inner Workings of Gut Immunology

Jennifer S. Kim; Hugh A. Sampson

Disclosures

Curr Opin Gastroenterol. 2012;28(2):99-103. 

In This Article

Abstract and Introduction

Abstract

Purpose of review How food protein becomes recognized as an allergen remains a fundamental question. Previous studies
indicated that the pathophysiology of food allergy is because of a skewed Th2 response to specific food glycoproteins. The focus has now shifted to understanding how a failure of regulatory mechanisms results in food allergy. This review summarizes the recent findings elucidating the small intestine's role in the pathophysiology of food allergy and the immune mechanisms of oral tolerance.
Recent findings Gut homeostasis and immunity occur via a complex interplay of innate and adaptive immune responses.
Immune exclusion is performed mainly by secretory IgA, although there are back-up mechanisms in place to induce oral tolerance when secretory IgA is lacking. Oral tolerance cannot occur in murine models lacking T regulatory cells, for which Foxp3+ is a key marker. Migration of Foxp3+ T cells from the mesenteric lymph nodes (MLNs) to the lamina propria occurs via gut-homing signals. Also in the MLNs are CD103+ dendritic cells, which drive the differentiation of Foxp3+ T cells in the presence of TGF-b and retinoic acid produced from dietary vitamin A. Lastly, microenvironmental signals from the microbiome can serve to enhance these interactions.
Summary We have focused primarily on local immunologic variables that may affect the induction of oral tolerance in the gut and the mechanisms elucidated in animal models. However, many other variables such as genetics, commensal microbiota, and diet are likely to be important factors.

Introduction

Food allergy is a growing problem among developed countries. Recent estimates approximate prevalence to be 4–8% in the United States.[1–4] Similar trends have been observed in other atopic disorders, such as asthma and atopic dermatitis. Interestingly, relatively few foods are responsible for more than 90% of food allergy. These include milk, egg, soy, and wheat (which are frequently outgrown), as well as peanut, tree nuts, fish, and shellfish (which tend to be life-long). Allergy to seeds, such as sesame and mustard, is also not uncommon.

Foods are introduced first to the gastrointestinal tract mucosa, which contains more lymphoid cells and produces more antibodies than any other site in the body. The gut has the critical task of determining friend from foe. Tolerance is the normal response to food antigens and is characterized by the secretion of IL-10 and TGF-β by T lymphocytes. IL-10 is a regulatory cytokine that favors T-cell anergy and also activates antigen-specific secretory IgA antibody production.[5] TGF-β has an immunosuppressive effect on B and T cells, maintaining immune nonresponsiveness to commensal bacterial and food antigens. It is also a switch factor for secretory IgA production.[6]

Normally, immunologic responses at the epithelium lead to a progression of events aimed at inactivating and removing offending antigens or microbes in addition to developing a tolerogenic response to nonpathogenic proteins, such as foods. Factors involved in oral tolerance induction include antigen dose (high dose and low dose) and form (soluble), as well as host characteristics such as microbiome content, genetics, age, and gastric acid suppression.

The failure to develop or the breakdown of oral tolerance leads to food allergy,[7,8] which may be IgE mediated, non-IgE mediated, or both. How food protein becomes recognized as an allergen in a naïve individual remains a fundamental question. Traditionally, the development of food allergy was primarily attributed to a skewed Th2 allergic response. However, it is now recognized that the failure of regulatory mechanisms may play a critical role in this Th2 skewing.[9]

This review will address the recent findings that have contributed to our understanding of the small intestine's role in the pathophysiology of food allergy and mechanisms of oral tolerance.

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