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

Yuxia Zhang, Fiona Collier, Gaetano Naselli, Richard Saffery, Mimi LK Tang, Katrina J. Allen, Anne-Louise Ponsonby, Leonard C. Harrison, Peter Vuillermin, on behalf of the BIS Investigator Group

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43 Citations (Scopus)

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.

Original languageEnglish
Article number321ra8
Number of pages8
JournalScience Translational Medicine
Volume8
Issue number321
DOIs
Publication statusPublished - 13 Jan 2016
Externally publishedYes

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