Abstract
Understanding the early events involved in the induction of immune tolerance to harmless environmental antigens and microbiota compounds could reveal potential targets for allergic disease therapy or prevention. Regulatory T cells (Treg), particularly induced Treg (iTreg), are crucial for the induction and maintenance of tolerance against environmental antigens including allergens. A decrease in the number and/or function of Treg or iTreg could represent an early predictor of allergy development. We analyzed proportional and functional properties of Treg in the cord blood of children of allergic mothers (neonates at high risk of allergy development) and healthy mothers (neonates with relatively low risk of allergy development). We observed a higher number of induced Treg in the cord blood of females compared to males, suggesting an impaired capacity of male immunity to set up tolerance to allergens, which could contribute to the higher incidence of allergy observed in male infants. The decreased proportion of iTreg in cord blood compared with maternal peripheral blood documents the general immaturity of the neonatal immune system. We observed a positive correlation in the demethylation of the Treg-specific demethylated region (TSDR) and the proportion of Treg in cord blood. Our data suggest that immaturity of the neonatal immune system is more severe in males, predisposing them to increased risk of allergy development.
Highlights
Allergic diseases are a highly diverse, multifactorial group of immunological disorders, characterized by unwarranted immune reactivity to and/or failure of tolerance to relatively innocuous exogenous antigens, i.e., allergens
The underlying cause of allergy is a dysregulation of the fine balance among various branches of the immune system which are orchestrated by specialized subpopulations of CD4+ T cells (e.g., Th1, Th2, Th9, Treg, Th17, Th22)
Contrary to our previous observations [42,47], we did not see any difference in Treg, induced Treg (iTreg) or natural Treg (nTreg) proportions between the cord blood of children of healthy and allergic mothers
Summary
Allergic diseases are a highly diverse, multifactorial group of immunological disorders, characterized by unwarranted immune reactivity to and/or failure of tolerance to relatively innocuous exogenous antigens, i.e., allergens. The underlying cause of allergy is a dysregulation of the fine balance among various branches of the immune system which are orchestrated by specialized subpopulations of CD4+ T cells (e.g., Th1, Th2, Th9, Treg, Th17, Th22) The roots of this dysregulation can be tracked to the prenatal period, when developing fetal immunity is maintained under Th2 bias in order to prevent harmful reactivity against antigenically foreign maternal determinants [1]. This Th2 bias needs to be postnatally retracted and a new balance among immune response branches must be established in order to avoid Th2- and immunoglobulin E (IgE)-mediated sensitization and hyper-responsiveness toward innocuous environmental antigens, which constitute the most common form of allergy.
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