Discussion
Dexamethasone-induced CD4+ FKBP51 expression is uniquely associated with worse asthma control in obese children with asthma and may underlie the corticosteroid resistance observed in this population.
Methods
High-dimensional flow cytometry of PBMC at baseline and after dexamethasone stimulation was performed to characterize lymphocyte subpopulations, T-lymphocyte polarization, proliferation (Ki-67+), and expression of the steroid-responsive protein FK506-binding protein 51 (FKBP51). T-lymphocyte populations were compared between obese and normal-weight participants, and an unbiased, unsupervised clustering analysis was performed. Differentially expressed clusters were compared with asthma control, adjusted for ICS and exhaled nitric oxide.
Results
In the obese population, there was an increased cluster of CD4+ T-lymphocytes expressing Ki-67 and FKBP51 at baseline and CD4+ T-lymphocytes expressing FKBP51 after dexamethasone stimulation. CD4+ Ki-67 and FKBP51 expression at baseline showed no association with asthma control. Dexamethasone-induced CD4+ FKBP51 expression was associated with worse asthma control in obese participants with asthma. FKBP51 expression in CD8+ T cells and CD19+ B cells did not differ among groups, nor did polarization profiles for Th1, Th2, Th9, or Th17 percentage.