Bronchial epithelial cells cultured from clinically stable lung allograft patients promote the development of macrophages from monocytes rather than dendritic cells (2009)

Author(s): Ward C, Eger K, Diboll J, Jones D, Haniffa MA, Fisher A, Brodlie M, Lordan JL, Corris PA, Hilkens CM

    Abstract: Introduction: Chronic allograft failure occurs as a result of alloimmune and non-allo-immune injury. Dendritic cells (DC) are thought to be crucial in regulating (allo)immune airway damage and interactions with epithelial cells are likely. Studies in human lung transplantation are limited however, and the available literature on DC inconsistent. Our study focused on the ex-vivo influence of primary bronchial epithelial cells derived from lung allografts on DC differentiation. Methods: Epithelial cell conditioned media (ECCM) were added to monocytes differentiating into DC under the influence of Interleukin-4 and Granulocyte Macrophage-Colony Stimulating Factor. The resultant cells were compared to DC cultured without ECCM and to monocyte-derived macrophages. Expression of typical DC (e.g. CD1a) and macrophage (e.g. CD14) markers was assessed by flow cytometry. Phenotypical assessments were complimented by functional studies of mannose receptor-mediated phagocytosis (FITC dextran uptake) and antigen-presenting capability (Mixed Lymphocyte Reactions). Results: Cells exposed to ECCM expressed statistically significantly, lower levels of CD1a than unexposed DC. CD14 expression was increased, as was phagocytic function. ECCM-cultured cells also expressed lower levels of T-cell co-stimulatory molecules, secreted an anti-inflammatory cytokine profile and had significantly reduced antigen-presenting capability. Conclusion: Using phenotypic and functional approaches our study has shown that ECCM from lung allografts drives the production of macrophage-like cells from monocytes, rather than DC. Our data suggest that epithelial cells may restrain airway DC and potential alloimmunity. It remains unclear whether the observed effect is specifically seen in lung transplant recipients or might be a general property of bronchial epithelial cells. It is possible that this may reflect a homeostatic inter-relationship between airway epithelial and DC populations, relevant both to lung allografts and the lung more generally.

      • Journal: Thorax
      • Volume: 64
      • Issue: 5
      • Pages: 430-435
      • Publisher: BMJ Group
      • Publication type: Article
      • Bibliographic status: Published

      Dr Malcolm Brodlie
      MRC Clinician Scientist, Clinical Senior Lecturer and Honorary Consultant Paediatric Respiratory Physician

      Julie Diboll
      Research Technician

      Professor Andrew Fisher
      Dean of Clinical Medicine and Professor of Respiratory Transplant Medicine

      Dr Catharien Hilkens
      Reader in Immunotherapy

      Dr Christopher Ward
      Senior Lecturer; Respiratory Medicine