Dendritic cell phenotype in severe asthma reflects clinical responsiveness to glucocorticoids. Issue 1 (18th December 2017)

• Record Type: Journal Article
• Authors: Chambers, E. S.; Nanzer, A. M.; Pfeffer, P. E.; Richards, D. F.; Martineau, A. R.; Griffiths, C. J.; Corrigan, C. J.; Hawrylowicz, C. M.
• Is Part Of: Clinical & experimental allergy. Volume 48:Issue 1(2018)
• Page Start: 13
• Page End: 22
• Publication Date: 2017-12-18
• Subjects: asthma -- dendritic cell -- glucocorticoid -- steroid resistant -- steroid sensitive -- T cells; Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.13061
• Languages: English
• ISSNs: 0954-7894

Abstract

Summary: Background: Subsets of patients with severe asthma remain symptomatic despite prolonged, high‐dose glucocorticoid therapy. We hypothesized that the clinical glucocorticoid sensitivity of these asthmatics is reflected in differences in peripheral blood dendritic cell subsets. Objective: To compare peripheral blood leucocyte 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 2 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 = .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 = .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 shows a differential response to oral prednisolone therapy.