Abstract
The immune system’s correct functioning requires a sophisticated balance between responses to continuous microbial challenges and tolerance to harmless antigens, such as self-antigens, food antigens, commensal microbes, allergens, etc. When this equilibrium is altered, it can lead to inflammatory pathologies, tumor growth, autoimmune disorders, and allergy/asthma. The objective of this review is to show the existing data on the importance of regulatory T cells (Tregs) on this balance and to underline how intrauterine and postnatal environmental exposures influence the maturation of the immune system in humans. Genetic and environmental factors during embryo development and/or early life will result in a proper or, conversely, inadequate immune maturation with either beneficial or deleterious effects on health. We have focused herein on Tregs as a reflection of the maturity of the immune system. We explain the types, origins, and the mechanisms of action of these cells, discussing their role in allergy and asthma predisposition. Understanding the importance of Tregs in counteracting dysregulated immunity would provide approaches to diminish asthma and other related diseases in infants.
Highlights
The objective of this review is to show the existing data on the importance of regulatory T cells (Tregs) on this balance and to underline how intrauterine and postnatal environmental exposures influence the maturation of the immune system in humans
Regulatory T cells are a specific CD4+ T cell population involved in peripheral tolerance by inhibiting autoreactive CD4+ T cells that have eluded negative selection in the thymus and controlling inflammation in diverse biological processes, such as infection, metabolic disease, tissue repair, cancer, and hypersensitivity reactions [1, 227]
In another study, Treg numbers were higher in asthmatic versus healthy children, and Tregs of children with AA show sufficient suppression of Th1/Th2 cytokines; whereas Tregs from infants with non-allergic asthma (NA) do not. These results suggest that the high number of Tregs in certain patients with AA might still not been sufficient to control the disease or additional mechanisms, such as deficiency in innate immune regulation, may be relevant for persistent inflammation [70, 73]
Summary
A high percentage of asthmatics (ninety percent) are diagnosed by 6 years of age, suggesting that the influence of intrauterine milieu and early life events such as atopic diseases and wheezing illnesses induced by respiratory viral infections are highly determinant for the development or not of asthma during childhood [66, 67] In this sense, abnormal regulatory T-cell function and/or numbers have been pointed to as the main cause of AA incidence and it has been observed that Tregs are already defective in the umbilical cord blood of newborns at a genetic risk of allergy [67, 68].
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