Goblet cells are derived from a FOXJ1-expressing progenitor in a human airway epithelium.
The overproduction of mucus is a key pathology associated with respiratory diseases, such as asthma and chronic obstructive pulmonary disease. These conditions are characterized by an increase in the number of mucus-producing goblet cells in the airways. We have studied the cellular origins of goblet cells using primary human bronchial epithelial cells (HBECs), which can be differentiated to form a stratified epithelium containing ciliated, basal and goblet cells. Treatment of differentiated HBEC cultures with the cytokine IL-13, an important mediator in asthma, increased the numbers of goblet cells and decreased the numbers of ciliated cells. To determine whether ciliated cells act as goblet cell progenitors, ciliated cells in HBEC cultures were hereditably labeled with enhanced green fluorescent protein (EGFP) using two lentiviral vectors, one which contained Cre recombinase under the control of a FOXJ1 promoter and a second Cytomegalovirus (CMV)-floxed-EGFP construct. The fate of the EGFP-labeled ciliated cells was tracked in HBEC cultures. Treatment with IL-13 reduced the numbers of EGFP-labeled ciliated cells compared with untreated cultures. In contrast, IL-13 treatment significantly increased the numbers of EGFP-labeled goblet cells. This study demonstrates that goblet cells formed in response to IL-13 treatment are in part or wholly derived from progenitors that express the ciliated cell marker, FOXJ1.
Novartis Institutes for Biomedical Research, Respiratory Disease Area, Horsham, West Sussex, UK.
Jonathan
J
Turner
Jan
J
Roger
Juliette
J
Fitau
Delphine
D
Combe
June
J
Giddings
Gino Van
GV
Heeke
Carol E
CE
Jones
D000818:Animals; D001980:Bronchi / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D020397:Goblet Cells / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018793:Interleukin-13 / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D010957:Plasmids / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea / Q000378:metabolism*
C106349:FOXJ1 protein, human; D051858:Forkhead Transcription Factors; D018793:Interleukin-13