TSLP receptor is not essential for house dust mite-induced allergic rhinitis in mice

Abstract

TSLP induces Th2 cytokine production by Th2 cells and various other types of cells, thereby contributing to Th2-type immune responses and development of allergic disorders. We found that house dust mite (HDM) extract induced TSLP production by nasal epithelial cells, suggesting that TSLP may be involved in development of HDM-induced allergic rhinitis (AR). To investigate that possibility in greater detail, wild-type and TSLP receptor-deficient (TSLPR^-/-) mice on the C57BL/6J background were repeatedly treated intranasally with HDM extract. The frequency of sneezing, numbers of eosinophils and goblet cells, thickness of submucosal layers, serum levels of total IgE and HDM-specific IgG1, and levels of IL-4, IL-5 and IL-13 in the culture supernatants of HDM-stimulated LN cells were comparable in the two mouse strains. Those findings indicate that, in mice, TSLPR is not crucial for development of HDM-induced AR.

Keywords: AR, allergic rhinitis; Allergy; HDM, house dust mites; House dust mite; Mouse; Rhinitis; TSLP receptor; TSLP, thymic stromal lymphopoietin; TSLPR, thymic stromal lymphopoietin receptor.

Fig. 1

TSLP induction by nasal epithelial cells in response to HDM extract. Nasal epithelial cells from wild-type mice were cultured in the presence and absence of HDM extract for 24 h, 48 h and 7 days. The levels of TSLP in the culture supernatants were determined by ELISA. Data show the mean±SEM (n=3). *p<0.05 and **p<0.01. The data show representative results from 3 independent experiments.

Fig. 2

TSLPR is not essential for immediate reaction during HDM-induced AR. Wild-type and TSLPR^-/- mice were treated intranasally with HDM extract or PBS. Sera were collected 48 h after the last inhalation. (A) The frequency of sneezing was counted for 5 min after the last HDM or PBS treatment. (B)The serum levels of total IgE and (C) HDM-specific IgG1 were determined by ELISA. Data show the mean±SEM (wild-type mice, n=4 [PBS] and n=6–8 [HDM]; and TSLPR^−/− mice, n=4 [PBS] and n=6-8 [HDM]).

Fig. 3

TSLPR is not essential for development of HDM-induced AR. Wild-type and TSLPR^−/− mice were treated intranasally with HDM extract or PBS. Tissues were harvested 48 h after the last inhalation. (A) The number of eosinophils in the nasal mucosa. (B) The number of goblet cells in the nasal mucosa. (C) The thickness of submucosal layers. (D) H&E and PAS staining of nasal mucosa sections. Arrow = eosinophil; arrowhead=goblet cell. Scale bar=20 µm. Data show the mean±SEM (wild-type mice, n=4 [PBS] and n=6-8 [HDM]; and TSLPR^−/− mice, n=4 [PBS] and n=6–8 [HDM]) (A, B and C). Data show representative results from 4 to 6 mice in each group (D).

Fig. 4

TSLPR is not required for induction and activation of HDM-specific LN cells. Wild-type and TSLPR^−/− mice were treated intranasally with HDM extract or PBS. Cervical LNs were harvested 48 h after the last inhalation. LN cells were cultured in the presence of HDM extract for 72 h. The levels of IL-4, IL-5 and IL-13 in the culture supernatants were determined by ELISA. Data show the mean±SEM (wild-type mice, n=4 [PBS] and n=6-8 [HDM]; and TSLPR^−/− mice, n=4 [PBS] and n=6-8 [HDM]) (A, B and C).