Dendritic cell phenotype in severe asthma reflects clinical responsiveness to glucocorticoids

Abstract

Background

Subsets of patients with severe asthma remain symptomatic despite prolonged, high dosage glucocorticoid therapy. We hypothesised that the clinical glucocorticoid sensitivity of these asthmatics is reflected in differences in peripheral blood dendritic cell subsets.

Objective

To compare peripheral blood leukocyte populations using flow cytometry at baseline and after 2 weeks of systemic glucocorticoid (steroid) treatment to identify immunological differences between steroid sensitive (SS) and steroid resistant (SR) asthmatics.

Methods

Adult severe asthmatics (SS n=12; SR n=23) were assessed for their response to two weeks of therapy with oral prednisolone. Peripheral blood was obtained before and after therapy and stained for lymphocyte (CD3, CD19, CD4, CD8 and Foxp3) and dendritic cell markers (Lineage negative [CD3, CD14, CD16, CD19, CD20, CD56], HLA-DR+, CD304, CD11c, ILT3 and CD86).

Results

A higher median frequency of myeloid DCs (mDCs) but not plasmacytoid DCs (pDCs) was observed in the blood of SR as compared to SS asthmatics (p=0.03). Glucocorticoid therapy significantly increased median B cell, but not T cell numbers in both cohorts, with a trend for increased numbers of Foxp3+ Tregs in SS (p=0.07), but not SR subjects. Oral prednisolone therapy significantly reduced the median numbers and frequencies of total DCs and pDCs in both SS and SR asthmatics. Interestingly the expression of HLA-DR and ILT3 was also reduced on pDCs in all patients. In contrast, therapy increased the median frequency of mDCs in SS, but reduced it in SR asthmatics.

Conclusions

Myeloid DC frequency is elevated in SR compared with SS asthmatics, and mDC show a differential response to oral prednisolone therapy.

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