Transdifferentiation of Clara Cell 10-kDa Protein Secreting Cells in Experimental Allergic Rhinitis

Abstract

The reasons for the down-regulated Clara cell 10-kDa protein (CC10) expression in allergic rhinitis (AR) are unclear and the airway remodeling in AR has received little attention. This study explores epithelium remodeling and the change of CC10 secreting cells in AR by using a murine model. AR murine models were established by ovalbumin sensitization and challenge. In some mice, dexamethasone was given before each challenge. Histological changes of nasal mucosa were examined by means of hematoxylin and eosin and periodic acid-Schiff staining. CC10 and trefoil factor family (TFF) 1 expression were evaluated by immunohistochemistry. In AR mice, both in turbinate and in septal mucosa, total cell number and the number of basal cells did not change; however, the number of dome-shaped cells decreased and the number of ciliated and goblet cells increased in turbinate mucosa, and the number of ciliated cells decreased and the number of goblet cells increased in septal mucosa. In turbinate mucosa, the number of CC10(+) cells (mainly dome-shaped cells) decreased whereas the number of TFF1(+) cells (mainly ciliated cells) increased. In septal mucosa, the number of CC10(+) and TFF1(+) cells (mainly ciliated cells) decreased simultaneously. Intermediate phenotypic goblet cells could express CC10 and TFF1. CC10 and TFF1 could be localized in the same cells. Dexamethasone reversed the changes of epithelium significantly. Allergen exposure leads to a possible transdifferentiation of CC10 secreting cells into TFF1 secreting cells and/or goblet cells in upper airways. Nasal turbinate and septal epithelium display different patterns of transdifferentiation.