Abstract
BackgroundThe imbalance between Th17 and Treg cells has been studied in various diseases including allergic asthma but their roles have not been fully understood in the development of the late phase asthmatic response.ObjectivesTo determine changes in Th17 and Treg cell numbers between isolated early responders (ERs) and dual responders (DRs) undergoing allergen inhalation challenge. To identify gene expression profiles associated with Th17 and Treg cells.Methods14 participants (8 ERs and 6 DRs) with mild allergic asthma underwent allergen inhalation challenge. Peripheral blood was collected prior to and 2 hours post allergen challenge. DNA methylation analysis was used to quantifiy the relative frequencies of Th17, Tregs, total B cells, and total T cells. Gene expression from whole blood was measured using microarrays. Technical replication of selected genes was performed using nanoString nCounter Elements.ResultsThe Th17/Treg ratio significantly increased in DRs compared to ERs post allergen challenge compared to pre-challenge. Genes significantly correlated to Th17 and Treg cell counts were inversely correlated with each other. Genes significantly correlated with Th17/Treg ratio included the cluster of genes of the leukocyte receptor complex located on chromosome 19q 13.4.ConclusionsTh17/Treg imbalance post-challenge may contribute to the development of the late phase inflammatory phenotype.
Highlights
The imbalance between a proinflammatory T helper 17 (Th17) and a regulatory T (Treg) cell phenotype may play a crucial role in allergic airway inflammation [1]
T cell, B cell and Th17 cell counts were significantly positively correlated with the genes targeted in epigenetic cell counting in both the microarray (Figure 1; top row) and nanoString (Figure 1; bottom row) platforms
Regulatory T (Treg) cell counts were not correlated with Forkhead box protein 3 (FOXP3) gene expression measured using microarrays but was significantly correlated using nanoString, suggesting greater sensitivity of the platform (Figure 1, red points)
Summary
The imbalance between a proinflammatory T helper 17 (Th17) and a regulatory T (Treg) cell phenotype may play a crucial role in allergic airway inflammation [1]. We have previously demonstrated that peripheral blood is a useful biological material with which to study changes in the blood transcriptome, proteome and metabolome of individuals with mild atopic asthma undergoing allergen inhalation challenge [13,14,15,16]. We have used qPCR based DNA methylation analysis to estimate the number of Th17 cells, Treg cells, T cells and B cells in peripheral blood of mild atopic asthmatics undergoing allergen inhalation challenge. We hypothesized that changes in specific immune cell counts in peripheral blood would be associated with the allergen-induced late phase asthmatic response. The imbalance between Th17 and Treg cells has been studied in various diseases including allergic asthma but their roles have not been fully understood in the development of the late phase asthmatic response
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