Cord blood monocyte–derived inflammatory cytokines suppress IL-2 and induce nonclassic “T _H 2-type” immunity associated with development of food allergy

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.

Pathogenic CD4 + T cells in patients with asthma

“…116–118 Treg cells can also undergo reprogramming toward a T H 2-like phenotype based on coexpression of Foxp3 and IL-4 in response to proinflammatory cytokines akin to those expressed in inflamed tissues. 119,120 At the level of gene transcription, miRNAs control the ability for Treg cells to acquire effector functions. This is illustrated by the ability for miR-17 to repress the Treg cell–stabilizing transcription factor Eos while derepressing genes encoding effector cytokines.…”

IgE cross-linking impairs monocyte antiviral responses and inhibits influenza-driven TH1 differentiation

“…4 Monocytes are also recruited to respiratory sites during viral infections E17 and allergen exposure, 5, E18 and implicated in food allergy development. 6 In addition, allergic stimulation via IgE cross-linking impacts monocyte functions including apoptosis, E19 cytokine secretion, and phagocytosis. 7 Defining IgE-mediated effects on monocyte antiviral responses could reveal additional pathways involved in atopic disease pathogenesis.…”

Transcriptional Profiling of Egg Allergy and Relationship to Disease Phenotype

“…Der p 2 and Der f 2 (from dust mite), Fel d 1 (cat allergen) and Can f 6 (dog allergen) are lipid-binding proteins that enhance signaling through TLR4 [27]. A recent report studying the immune profile of cord blood samples demonstrated that monocyte responsiveness to LPS was significantly increased in infants who developed food allergy, and that monocyte-derived inflammatory cytokines could promote the development of Th2 cells [28]. Therefore, there may be a unique contribution of TLR, and TLR4 associated pathways particularly, in the generation of inappropriate immune responses to egg in allergic individuals.…”