Inhaled corticosteroid use is associated with increased circulating T regulatory cells in children with asthma

Anne Marie Singh,Lisa Salazar,Robert F Lemanske,James E Gern,Christopher Tisler,Kathy A Roberg,Douglas Dasilva,Ronald Gangnon,Kristjan Burmeister,Christine M Seroogy,Paul Dahlberg,Michael D Evans,Tressa Pappas

doi:10.1186/1476-7961-11-1

Anne Marie Singh, Lisa Salazar + Show 11 more

Open Access

https://doi.org/10.1186/1476-7961-11-1

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Abstract

BackgroundT regulatory (Treg) cells are important in balancing immune responses and dysregulation of Treg cells has been implicated in the pathogenesis of multiple disease states including asthma. In this study, our primary aim was to determine Treg cell frequency in the peripheral blood of children with and without asthma. The secondary aim was to explore the association between Treg cell frequency with allergen sensitization, disease severity and medication use.MethodsPeripheral blood mononuclear cells from healthy control subjects (N = 93) and asthmatic children of varying disease severity (N = 66) were characterized by multi-parameter flow cytometry.ResultsOur findings demonstrate that children with asthma had a significantly increased frequency of Treg cells compared to children without asthma. Using a multivariate model, increased Treg cell frequency in children with asthma was most directly associated with inhaled corticosteroid use, and not asthma severity, allergic sensitization, or atopic status of the asthma.ConclusionWe conclude that low dose, local airway administration of corticosteroids is sufficient to impact the frequency of Treg cells in the peripheral blood. These data highlight the importance of considering medication exposure when studying Treg cells and suggest inhaled corticosteroid use in asthmatics may improve disease control through increased Treg cell frequency.

Highlights

The CD25+ T regulatory (Treg) cell, a widely accepted T cell subset with immune suppressive properties, was initially thought to exist primarily to prevent autoimmune diseases [1]
Asthma diagnosis and disease severity were significantly associated with perennial allergen sensitization and total IgE, but not seasonal allergen sensitization (Table 1)
To better understand the relationships among Treg cells, allergic sensitization and asthma, we examined the association between total IgE levels, allergen-specific sensitization, and Treg cell frequency

Summary

Introduction

The CD25+ T regulatory (Treg) cell, a widely accepted T cell subset with immune suppressive properties, was initially thought to exist primarily to prevent autoimmune diseases [1]. Increasing evidence suggests that Treg cells are important in varied immune responses, including allergic diseases [2,3,4,5,6]. We used multi-parameter flow cytometry to investigate the frequency of Treg cells in the peripheral blood of children ages 7–8 years with or without asthma. The frequency of Treg cells was further analyzed in relationship to disease severity, allergic sensitization and medication use. T regulatory (Treg) cells are important in balancing immune responses and dysregulation of Treg cells has been implicated in the pathogenesis of multiple disease states including asthma. Our primary aim was to determine Treg cell frequency in the peripheral blood of children with and without asthma. The secondary aim was to explore the association between Treg cell frequency with allergen sensitization, disease severity and medication use

Methods

Results

Conclusion