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


Zhang, Y; Collier, F; Naselli, G; Saffery, R; Tang, ML; Allen, KJ; Ponsonby, AL; Harrison, LC; Vuillermin, P; BISInvestigator Group,
2016-01-13
Sci Transl Med
Journal Article
8
321
321ra8
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-1beta, IL-6, and tumor necrosis factor-alpha) in response to lipopolysaccharide. In the presence of the mucosal cytokine transforming growth factor-beta, 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 naive 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.
AAAS
Population Health and Immunity
10.1126/scitranslmed.aad4322
26764159
Refer to article for additional funding acknowledgements
Refer to copyright notice on published article.

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Creation Date 2016-01-29 11:46:12 Last Modified 2016-01-29 02:25:12