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Sci Transl Med. 2016 Jan 13;8(321):321ra8. doi: 10.1126/scitranslmed.aad4322.

Cord blood monocyte-derived inflammatory cytokines suppress IL-2 and induce nonclassic "T(H)2-type" immunity associated with development of food allergy.

Author information

1
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. The University of Melbourne, Parkville, Victoria 3010, Australia. Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China. yzhang@wehi.edu.au harrison@wehi.edu.au peter.vuillermin@deakin.edu.au.
2
Barwon Health, Geelong, Victoria 3220, Australia. Deakin University, Geelong, Victoria 3216, Australia.
3
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
4
The University of Melbourne, Parkville, Victoria 3010, Australia. Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia.
5
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. The University of Melbourne, Parkville, Victoria 3010, Australia. yzhang@wehi.edu.au harrison@wehi.edu.au peter.vuillermin@deakin.edu.au.
6
The University of Melbourne, Parkville, Victoria 3010, Australia. Barwon Health, Geelong, Victoria 3220, Australia. Deakin University, Geelong, Victoria 3216, Australia. Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia. yzhang@wehi.edu.au harrison@wehi.edu.au peter.vuillermin@deakin.edu.au.

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 (T(H)2)-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 (nT(reg)) 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 nT(reg) and diverted the differentiation of both nT(reg) 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.

Comment in

PMID:
26764159
DOI:
10.1126/scitranslmed.aad4322
[Indexed for MEDLINE]

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