Distinct characteristics of Tregs of newborns of healthy and allergic mothers.

Viktor Černý,Libuše Kolářová,Ludmila Prokešová,Petra Petrásková,Kristýna Boráková,Olga Novotná,Jiří Hrdý,Susmit Suvas

doi:10.1371/journal.pone.0207998

Viktor Černý, Libuše Kolářová + Show 6 more

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https://doi.org/10.1371/journal.pone.0207998

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Abstract

Allergic diseases represent a major issue in clinical and experimental immunology due to their high and increasing incidence worldwide. Allergy status of the mother remains the best predictor of an individual’s increased risk of allergy development. Dysregulation of the balance between different branches of immune response, chiefly excessive polarization towards Th2, is the underlying cause of allergic diseases. Regulatory T cells (Tregs) play a pivotal role in the timely establishment of physiological immune polarization and are crucial for control of allergy. In our study we used flow cytometry to assess Tregs in cord blood of newborns of healthy (n = 121) and allergic (n = 108) mothers. We observed a higher percentage of Tregs (CD4+CD25+CD127lowFoxP3+) in cord blood of children of allergic mothers. However, the percentage of cells expressing extracellular (PD-1, CTLA-4, GITR) and intracellular (IL-10, TGF-β) markers of function was lower (significantly for PD-1 and IL-10) within Tregs of these children. Furthermore, Helios- induced Tregs in the cord blood of children of allergic mothers were decreased. These results were supported by a decrease in plasma levels of IL-10 and TGF-β in cord blood of newborns of allergic mothers, implying lower tolerogenic capacity on the systemic level. Taken together, these findings reflect deficient function of Tregs in the group with higher risk of allergy development. This may be caused by a lower maturation status of the immune system, specifically Tregs, at birth. Such immaturity may represent an important mechanism involved in the increased risk of allergy in children of allergic mothers.

Highlights

Allergic diseases belong to the most common and important medical conditions
Tregs were tested for their surface functional markers (PD-1, CTLA-4, GITR) and intracellular cytokines (IL-10, TGF-β) to reveal possible differences in functional characteristics
After adding antibodies against Helios, a transcription factor characteristic for natural but not induced Tregs, we revealed a higher proportion of FoxP3+Helios+ natural Tregs (nTregs) (Fig 2B; p = 0.0149) and a lower proportion of FoxP3+Helios- iTregs (Fig 2C; p = 0.0175) in CD4+CD25+CD127low Tregs of children of allergic mothers

Summary

Introduction

Allergic diseases belong to the most common and important medical conditions. The early events leading to the development of allergy in predisposed infants remain to be conclusively elucidated. The hygiene hypothesis is a major theory, postulating that lower exposure to microbes typical for the more developed countries may delay the development of the immune system and alter the balance among immune response branches (e.g. Th1, Th2, Treg, Th17), facilitating allergy. Persistence of the Th2 bias predisposes towards allergy development; Th1 and Th17 responses play important roles in anti-infectious immunity, but under certain conditions can lead to the development of autoimmune diseases. Regulatory T cells (Tregs) are the master T lymphocyte population overseeing this fine tuning and controlling potential development of pathological reactions including allergy-associated Th2 responses [2]

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