Abstract
BackgroundMaternal allergic disease history and impaired regulatory T-cells (Tregs) are critical risk factors for allergy development in children. However, the mechanisms that underlie these risk factors remain poorly defined. Therefore, the aim of this study was to assess whether maternal allergies affect the Tregs of offspring and lead to allergy development in childhood.MethodsA total of 332 mothers of healthy newborns (234 from no allergic mothers, 98 from allergic mothers) were recruited to this study. Detailed questionnaires were administered yearly to determine the allergy status of the mothers and the newborns from birth to 3 years of age. Cord blood samples obtained at the time of birth were analysed for Treg counts, as well Treg activity, based on their response to Toll-like receptor (TLR) stimuli such as lipid A (LPA) and peptidoglycans (PPG). Surface markers, associated genes, suppressive capacity, and cytokine levels of Tregs were also measured. Possible correlations between Treg activity and maternal or neonate allergies were assessed. In addition, environmental microbial content and other known risk factors for allergies were measured.ResultsCord blood mononuclear cells (CBMCs) from offspring with allergic mothers showed fewer CD4+CD25+FOXP3+ T cells, lower expression levels of associated genes, and reduced cytokine production of interleukin (IL)-10 and interferon-γ (P < 0.05), especially via the PPG-TLR2 pathway. Suppression of effector T cells by Tregs from children of mothers with allergies was impaired, especially IL-13 production by Type 2 T helper (Th2) cells (P = 0.026). Children who developed allergies in the first 3 years of life had lower numbers of CD4+CD25+FOXP3+ T cells and reduced FOXP3 expression and IL-10 production as newborns (P < 0.05). Maternal allergic background was identified as a risk factor for allergy development in the children (Odds ratio (OR) = 2.46, 95 % CI = 1.05–5.79); while declining Treg numbers, IL-10 production, and FOXP3 expression in neonates (PPG and LPA stimulated) were identified as independent risk factors for allergic diseases in offspring at 3 years of age after adjusting for maternal allergic history and environmental factors (P < 0.05).ConclusionMaternal allergy correlated with impaired Tregs in neonates, and this could enhance the susceptibility of offspring to allergic diseases in early childhood due to an imbalance of Th1 and Th2 cells.
Highlights
Maternal allergic disease history and impaired regulatory T-cells (Tregs) are critical risk factors for allergy development in children
Immune system stimulation may be critical to early immune modulation, and several studies have reported that young children growing up in environments rich in microbial stimuli have a lower risk of allergy [13, 14]
A follow-up study was conducted for the 273 children for whom a completed follow-up questionnaire was completed at 0–3 years of age (Table 2)
Summary
Maternal allergic disease history and impaired regulatory T-cells (Tregs) are critical risk factors for allergy development in children. Some prospective cohort studies of Western countries have shown that susceptibility to allergic diseases in children may occur early in life [4,5,6], and during this time period regulatory T-cells (Tregs) could be involved. The suppressive capacity of Tregs is required to maintain the balance of T helper (Th) cells, including Th1, Th2, and Th17 cells Unchecked proliferation of these Th cell populations has been shown to play a key role in the pathogenesis of allergic diseases. Activation of the TLR2/4 pathways has been shown to upregulate Tregs and induce cytokine secretion in both children and animal models with allergy development [13,14,15]
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