BACKGROUND: Glucocorticosteroids (GCs) are highly effective in mitigating allergic inflammation. In this study, we investigate the effects of dexamethasone (DEX) on regulatory T cells (Tregs) in a murine model of allergic rhinitis (AR). METHODS: BALB/c mice were sensitized to ovalbumin (OVA) followed by intranasal OVA challenge. Mice in the treatment group received DEX by intraperitoneal injection (5 mg/kg/day) 1 hour before the OVA challenge. Further, CD4(+) CD25(-) T cells from the spleens were cultured in presence of DEX. The effects of DEX on CD4(+) Foxp3(+) T cells were then assessed in vivo as well as in vitro. RESULTS: Frequencies of sneezing and scratching decreased significantly in the DEX-treated group compared to that in the OVA group. Histopathological analyses showed that DEX restored the destroyed and discontinuous ciliated epithelium of the nasal mucosa in the OVA group. Moreover, DEX inhibited the production of interleukin (IL)-4, IL-5, and IL-13 in the nasal cavity lavage fluid in this group. We also observed a significant increase in the percentage of CD4(+) Foxp3(+) T cells in the OVA group. In vivo, DEX treatment significantly decreased the number of CD4(+) Foxp3(+) T cells. However, in vitro, the proportion of these cells increased in the presence of DEX. Furthermore, the number of late stage apoptotic CD4(+) T cells was also significantly increased upon exposure to DEX. CONCLUSION: DEX therapy effectively suppresses AR symptoms, but does not result in the expected increase in the frequency of Tregs in vivo. Thus, whether GCs exert immunosuppressive effects by influencing the number of Tregs remains unresolved.
BACKGROUND: Glucocorticosteroids (GCs) are highly effective in mitigating allergic inflammation. In this study, we investigate the effects of dexamethasone (DEX) on regulatory T cells (Tregs) in a murine model of allergic rhinitis (AR). METHODS: BALB/c mice were sensitized to ovalbumin (OVA) followed by intranasal OVA challenge. Mice in the treatment group received DEX by intraperitoneal injection (5 mg/kg/day) 1 hour before the OVA challenge. Further, CD4(+) CD25(-) T cells from the spleens were cultured in presence of DEX. The effects of DEX on CD4(+) Foxp3(+) T cells were then assessed in vivo as well as in vitro. RESULTS: Frequencies of sneezing and scratching decreased significantly in the DEX-treated group compared to that in the OVA group. Histopathological analyses showed that DEX restored the destroyed and discontinuous ciliated epithelium of the nasal mucosa in the OVA group. Moreover, DEX inhibited the production of interleukin (IL)-4, IL-5, and IL-13 in the nasal cavity lavage fluid in this group. We also observed a significant increase in the percentage of CD4(+) Foxp3(+) T cells in the OVA group. In vivo, DEX treatment significantly decreased the number of CD4(+) Foxp3(+) T cells. However, in vitro, the proportion of these cells increased in the presence of DEX. Furthermore, the number of late stage apoptotic CD4(+) T cells was also significantly increased upon exposure to DEX. CONCLUSION:DEX therapy effectively suppresses AR symptoms, but does not result in the expected increase in the frequency of Tregs in vivo. Thus, whether GCs exert immunosuppressive effects by influencing the number of Tregs remains unresolved.
Authors: Carina Matos; Katrin Peter; Laura Weich; Alice Peuker; Gabriele Schoenhammer; Tobias Roider; Sakhila Ghimire; Nathalie Babl; Sonja Decking; Martina Güllstorf; Nicolaus Kröger; Kathrin Hammon; Wolfgang Herr; Klaus Stark; Iris M Heid; Kathrin Renner; Ernst Holler; Marina Kreutz Journal: Front Immunol Date: 2022-01-04 Impact factor: 7.561