Research ArticleALLERGY

Cord blood monocyte–derived inflammatory cytokines suppress IL-2 and induce nonclassic “TH2-type” immunity associated with development of food allergy

Science Translational Medicine  13 Jan 2016:
Vol. 8, Issue 321, pp. 321ra8
DOI: 10.1126/scitranslmed.aad4322

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Fighting food allergy

For people with food allergies, a slice of pizza or a peanut butter sandwich can be deadly. Yet despite the increasing prevalence of food allergy, little is known as to the immunological causes. Now, Zhang et al. report that infants who later developed food allergy had altered immunity at birth. Cord blood from these infants had more monocytes compared with CD4+ T cells and decreased numbers of regulatory T cells. Moreover, the monocytes from food-allergic infants secreted more inflammatory cytokines than those from healthy infants. These cytokines suppressed interleukin-2 (IL-2) expression by CD4+ T cells and skewed differentiation of these cells to a nonclassical T helper 2 (TH2) phenotype. Anti-inflammatory strategies should therefore be considered in preventing food allergy in these individuals.

Abstract

Food allergy is a major health burden in early childhood. Infants who develop food allergy display a proinflammatory immune profile in cord blood, but how this is related to interleukin-4 (IL-4)/T helper 2 (TH2)–type immunity characteristic of allergy is unknown. In a general population-derived birth cohort, we found that in infants who developed food allergy, cord blood displayed a higher monocyte to CD4+ T cell ratio and a lower proportion of natural regulatory T cell (nTreg) in relation to duration of labor. CD14+ monocytes of food-allergic infants secreted higher amounts of inflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor–α) in response to lipopolysaccharide. In the presence of the mucosal cytokine transforming growth factor–β, these inflammatory cytokines suppressed IL-2 expression by CD4+ T cells. In the absence of IL-2, inflammatory cytokines decreased the number of activated nTreg and diverted the differentiation of both nTreg and naïve CD4+ T cells toward an IL-4–expressing nonclassical TH2 phenotype. These findings provide a mechanistic explanation for susceptibility to food allergy in infants and suggest anti-inflammatory approaches to its prevention.

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