Oral ingestion of peanut has an increased likelihood of inducing oral tolerance in the majority of children at a high-risk of peanut allergy with atopic dermatitis, compared with epicutaneous exposure to peanut protein in children with atopic dermatitis and impaired skin barrier, which has an increased likelihood of allergic IgE sensitization.
a | In the induction of oral tolerance, dietary fibre is digested by probiotic bacteria to release short-chain fatty acids (SCFA; for example butyrate, which acts via GPR109A) that then stimulate dendritic cells (DC) to produce IL-10 and to induce regulatory T cells (T reg). b | Conversely, S. aureus and its toxins (for example, staphylococcal enterotoxin B; SEB25) can lead to inflammation by inducing T-cell-independent expansion of B cells, which initiates the production of thymic stromal lymphopoietin (TSLP) from keratinocytes, and stimulates mast cell degranulation, resulting in type 2 T helper cell (T H2) skewing. S. aureus also disrupts proteolytic balance in the skin by inducing multiple metalloproteases in dermal fibroblasts. DCs secrete IL-4, IL-13 and IL-6 that stimulate generation of T H2 skewed effector T cells. T H2 CD4 + T cells secrete IL-4 that induces IgE production by B cells. Failure to develop oral tolerance can be influenced by lack of ingestion of regular doses of peanut, combined with intermittent exposure to trace amounts in the diet, inflammation in the gastrointestinal tract, high gastric pH, low levels of digestive enzymes, gut dysbiosis and increased intestinal permeability or immune defects resulting in deficiency of FOXP3 (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome; see Box 1) or IgA (selective IgA deficiency, common variable deficiency). TGFβ, transforming growth factor β.