The Th17 pathway in Cystic Fibrosis lung disease
Author(s)
Tan, Hui-leng
Type
Thesis
Abstract
In contrast to the neutrophilic inflammation found in the airway lumen, lymphocytes
predominate in the airway wall of Cystic fibrosis (CF) patients. The Th17 pathway could play
an important role in CF, as IL-17, secreted by Th17 lymphocytes, is proinflammatory,
stimulates neutrophil recruitment and has been detected in CF sputum.
This thesis investigates the hypothesis that T lymphocytes, in particular Th17 lymphocytes,
are present in the CF airway wall and activation of the Th17 pathway is CF specific.
Lymphocyte populations were characterised in endobronchial biopsies of children with CF,
non-CF bronchiectasis and controls and related to clinical status, microbiological cultures and
inflammation (cells and soluble factors) in bronchoalveolar lavage fluid (BALF). In parallel,
lymphoid aggregates seen in the nasal mucosa of CF mice were investigated.
Immunohistochemistry was performed on these endobronchial biopsies, staining for CD4,
CD8 and IL-17. Cellular sources of IL-17 were determined following development of a novel
immunofluorescence double staining protocol. Cells and cytokine levels were measured in
BALF. Flow cytometry analysis of the nasal mucosa of CF and wild type mice was
performed.
Significant differences in T helper (CD4+) cells but not cytotoxic (CD8+) T cells were found
between patient groups. Established CF and non-CF bronchiectasis samples had higher
numbers of IL-17+ cells than controls; newly diagnosed CF patients had intermediate counts.
Double staining confirmed there were Th17 lymphocytes in the submucosa of these biopsies.
IL-17+ neutrophils, !"T cells and natural killer T cells were also identified. CF mice were
also shown to have CD4+IL-17+ cells in their nasal mucosa.
In conclusion, Th17 lymphocytes are present in the airway submucosa in CF and represent
one of a number of sources of IL-17. Non-CF bronchiectasis patients had similar numbers of
IL-17+ cells, suggesting activation of the Th17 pathway is not CF specific.
predominate in the airway wall of Cystic fibrosis (CF) patients. The Th17 pathway could play
an important role in CF, as IL-17, secreted by Th17 lymphocytes, is proinflammatory,
stimulates neutrophil recruitment and has been detected in CF sputum.
This thesis investigates the hypothesis that T lymphocytes, in particular Th17 lymphocytes,
are present in the CF airway wall and activation of the Th17 pathway is CF specific.
Lymphocyte populations were characterised in endobronchial biopsies of children with CF,
non-CF bronchiectasis and controls and related to clinical status, microbiological cultures and
inflammation (cells and soluble factors) in bronchoalveolar lavage fluid (BALF). In parallel,
lymphoid aggregates seen in the nasal mucosa of CF mice were investigated.
Immunohistochemistry was performed on these endobronchial biopsies, staining for CD4,
CD8 and IL-17. Cellular sources of IL-17 were determined following development of a novel
immunofluorescence double staining protocol. Cells and cytokine levels were measured in
BALF. Flow cytometry analysis of the nasal mucosa of CF and wild type mice was
performed.
Significant differences in T helper (CD4+) cells but not cytotoxic (CD8+) T cells were found
between patient groups. Established CF and non-CF bronchiectasis samples had higher
numbers of IL-17+ cells than controls; newly diagnosed CF patients had intermediate counts.
Double staining confirmed there were Th17 lymphocytes in the submucosa of these biopsies.
IL-17+ neutrophils, !"T cells and natural killer T cells were also identified. CF mice were
also shown to have CD4+IL-17+ cells in their nasal mucosa.
In conclusion, Th17 lymphocytes are present in the airway submucosa in CF and represent
one of a number of sources of IL-17. Non-CF bronchiectasis patients had similar numbers of
IL-17+ cells, suggesting activation of the Th17 pathway is not CF specific.
Date Issued
2011-09
Date Awarded
2012-05
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Bush, Andrew
Davies, Jane
Lloyd, Clare
Sponsor
National Heart and Lung Institute
Publisher Department
National Heart and Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Medicine (Research) MD (Res)