Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 8, Issue 321, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aad4322
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Funding
- Australian National Health and Medical Research Council (NHMRC) [1037321, 1029927, 1082307, 607370]
- Juvenile Diabetes Research Foundation [17-2013-547]
- Walter and Eliza Hall Institute Catalyst Fund [45941]
- National Health and Medical Research Council of Australia [1082307] Funding Source: NHMRC
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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-1 beta, 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 nT(reg) and diverted the differentiation of both nTreg and naive CD4(+) T cells toward an IL-4-expressing nonclassical T(H)2 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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