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Dendritic cell phenotype in severe asthma reflects clinical responsiveness to glucocorticoids
Author(s) -
Chambers E. S.,
Nanzer A. M.,
Pfeffer P. E.,
Richards D. F.,
Martineau A. R.,
Griffiths C. J.,
Corrigan C. J.,
Hawrylowicz C. M.
Publication year - 2018
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13061
Subject(s) - medicine , immunology , plasmacytoid dendritic cell , dendritic cell , glucocorticoid , foxp3 , cd14 , cd19 , myeloid , t cell , cd8 , prednisolone , immune system
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 ( CD 3, CD 19, CD 4, CD 8 and Foxp3) and dendritic cell markers (Lineage negative [ CD 3, CD 14, CD 16, CD 19, CD 20, CD 56], HLA ‐ DR +, CD 304, CD 11c, ILT 3 and CD 86). Results A higher median frequency of myeloid DC s ( mDC s) but not plasmacytoid DC s ( pDC s) 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 DC s and pDC s in both SS and SR asthmatics. Interestingly, the expression of HLA ‐ DR and ILT 3 was also reduced on pDC s in all patients. In contrast, therapy increased the median frequency of mDC s 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.