The Roles and Mechanisms of Gut Microbiota in Food Allergy

Figure 1

Immune tolerance and tolerance breakdown to food antigens. (a) Under homeostatic states, food antigens in the gastrointestinal lumen pass into the submucosa by passaging through gaps between epithelial cells or by transporting through epithelial cells, M cells, or goblet cells. CX3CR1⁺ macrophages may also sample antigens by extending dendrites between epithelial cells. Transported antigens are sampled to CD103⁺ DCs in the lamina propria. Antigen-loaded DCs migrate to the mesenteric lymph nodes where these DCs produce TGF-β and RA, thereby inducing naive T cells to differentiate into antigen-specific Foxp3⁺ Treg cells. Treg cells home back to the gut and regulate B cell antibody class switching to IgA via production TGF-β. IgA is transported into the intestinal lumen and excludes luminal food antigens. (b) Tolerance breakdown is characterized by the transformation of CD103⁺ DCs from inducing Treg cells to proallergic Th2 effector cells. Exposure to certain PAMPs or injury to the epithelium (which leads to the expression of IL-25, IL-33, and TSLP) induces mucosal DCs to acquire a phenotype that favors Th2 cell priming when induced by the food antigens. Th2 cells produce IL-4 that stimulates many aspects of allergic response, including driving IgE switching in B cells, promoting mast cell survival, enhancing the further expansion of Th2 cells, and suppressing the function of tolerogenic Treg cells. ILC2s also produce IL-4 and IL-13 to block Treg cell function. M cell: microfold cell; CX3CR1⁺: CX3C-chemokine receptor 1; DCs: dendritic cells; TGF-β: transforming growth factor-β; RA: retinoic acid; Foxp3⁺ Treg cells: forkhead box P3 regulatory T cells; IgA: immunoglobulin A; IgE: immunoglobulin E; Th2 cell: T helper 2 cell; PAMPs: pathogen-associated molecular patterns; IL-25: interleukin-25; TSLP: thymic stromal lymphopoietin; ILC2s: group 2 innate lymphoid cells.