Cord blood monocyte-derived inflammatory cytokines suppress IL-2 and induce nonclassic "TH2-type" immunity associated with development of food allergy
- Author(s)
- Zhang, Y; Collier, F; Naselli, G; Saffery, R; Tang, ML; Allen, KJ; Ponsonby, AL; Harrison, LC; Vuillermin, P; BISInvestigator Group,;
- Details
- Publication Year 2016-01-13,Volume 8,Issue #321,Page 321ra8
- Journal Title
- Sci Transl Med
- Publication Type
- Journal Article
- 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-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.
- Publisher
- AAAS
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 26764159
- Publisher's Version
- https://doi.org/10.1126/scitranslmed.aad4322
- NHMRC Grants
- NHMRC/1037321,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-01-29 11:46:12
Last Modified: 2016-01-29 02:25:12