%0 Journal Article %A Jane Falconer %A Malcolm Brodlie %A Sonya Carnell %A Anthony de-Soyza %A James Lordan %A Paul Corris %A Catharien Hilkens %A Chris Ward %T Epithelial cell regulation of immunity in cystic fibrosis %D 2012 %J European Respiratory Journal %P P1442 %V 40 %N Suppl 56 %X Introduction: Despite clinical importance, the adaptive immune system in cystic fibrosis (CF) lung disease has been sparsely studied.Methods: We isolated CF primary human bronchial epithelial cells (PBEC) and assessed their modulation of monocyte-derived dendritic cell (moDC) function and downstream T cell activation, hypothesising that epithelial cells skew immunity to favour chronic infection and lung damage in CF. Healthy monocytes were cultured with conditioned medium from 6 steady-state CF patient PBEC during moDC differentiation with IL-4 and GM-CSF.Results: Compared to control moDC, epithelial cell conditioned moDC were tolerogenic and macrophage-like (↓CD1a, ↓ CD86, ↑CD14 and ↑ IL-10), inducing low T cell proliferation and interferon-γ production in an allogeneic mixed lymphocyte reaction (MLR). Stimulation of PBEC or direct stimulation of moDC with clinically isolated Burkholderia cenocepacia whole cell lysate gave a mature, highly stimulatory moDC phenotype while Pseudomonas aeruginosa induced poor maturation and a less potent T cell response.Figure 1. Steady state moDC phenotype and function altered by PBEC derived soluble factors. (MFI - median fluorescence intensity, CPM - counts per minute).Conclusion: CF epithelial cells secrete factors which contribute to immune tolerance. CF pathogens may have a variable ability to overcome this regulation and induce an immune response which may favour chronic infection by Pseudomonas aeruginosa. %U https://erj.ersjournals.com/content/erj/40/Suppl_56/P1442.full.pdf