Mucosal antibodies in the regulation of tolerance and allergy to foods

Abstract

The intestinal mucosa is densely packed with antibody-secreting B cells, the majority of which produce IgA. Mucosal antibodies have traditionally been thought of as neutralizing antibodies that exclude antigens, but they also function in antigen sampling, allowing for selective transcytosis of antigens from the intestinal lumen. IgE-mediated antigen uptake can facilitate the development of allergic reactions to foods, but emerging evidence indicates that IgG-mediated antigen uptake may also play an important role in the development of immune tolerance to foods, particularly in the neonate. This review will focus on the role of intestinal immunoglobulins in the development of clinical tolerance and allergy to food antigens.

Figure 1. Tolerogenic and immunogenic Roles of FcRn in mucosal immunity

In the neonate, IgG and antigens derived from the breast milk can be selectively taken up by an FcRn-dependent mechanism in the gastrointestinal tract. The immune consequence is active tolerance, mediated by CD4+ CD25+ Foxp3+ regulatory T cells that are induced by DCs exposed to IgG-antigen immune complexes. In the adult intestine, host production of antimicrobial IgG antibodies can facilitate the uptake of luminal microbial antigens through an FcRn-dependent mechanism. IgG-antigen complexes are taken up by dendritic cells, and drive a response that can be host-protective, resulting in pathogen clearance, or pathogenic, resulting in inflammation.

Figure 2. Mucosal antibodies in the regulation of tolerance and allergy to foods

IgA secreted across the epithelium can bind and neutralize food allergens, and contribute to clinical tolerance to foods by preventing entry and interaction with mucosal immune cells. Secretory IgA bound to antigen can also be selectively taken up across the Peyer’s patch, but the consequence of that uptake in the context of food allergy has not yet been addressed. IgG and IgE can be secreted across the epithelium by FcRn and CD23, respectively. IgG-facilitated antigen uptake via FcRn contributes to the development of active immune tolerance in the neonate. In contrast, IgE-facilitated antigen uptake via CD23 contributes to clinical reactivity by enhancing the delivery of IgE-antigen complexes to allergic effector cells. Therapeutic approaches that promote food-specific IgA or IgG production in the gut, or inhibit antigen uptake via CD23, may be beneficial for the development of food-specific tolerance.