Th9 cells induce steroid-resistant bronchial hyperresponsiveness in mice.

Background: Reduced responsiveness to corticosteroid therapy is a major problem for patients with severe asthma. Although Th9 cells, along with Th2 cells, facilitate antigen-induced airway eosinophilia and bronchial hyperresponsiveness (BHR), the sensitivity of Th9 cell-mediated responses to steroid therapy remains unknown. In this study, we investigated the effect of dexamethasone (Dex) on antigen-induced airway inflammation in Th9 cell-transferred mice.
Methods: Ovalbumin (OVA)-specific Th2 and Th9 cells were polarized from the CD4 ⁺ T cells of DO11.10/RAG-2 ^-/- mice. BALB/c mice were adoptively transferred with Th2 or Th9 cells and challenged with OVA. Dex treatment was performed twice, at 1 h before and at 24 h after the OVA challenge. Following treatment, the number of inflammatory cells in the bronchoalveolar lavage fluid and the bronchial responsiveness to inhaled methacholine were determined.
Results: In both the Th2 and Th9 cell-transferred mice, substantial accumulation of eosinophils in the lungs and BHR were induced by challenge with the specific antigen. In the Th2 cell-transferred mice, these responses were significantly diminished by Dex treatment. In contrast, neither cellular infiltration nor BHR was affected by Dex treatment in the Th9 cell-transferred mice, although the Th9 cells substantially expressed glucocorticoid receptor α. Accordingly, antigen-induced interleukin-9 expression in the Th9 cells was attenuated by Dex treatment at least in vitro. Antigen-induced lung infiltration of infused Th2 cells but not Th9 cells was significantly suppressed by Dex.
Conclusions: In contrast to Th2-mediated responses, Th9-mediated airway inflammation was not affected by Dex. Th9 cells might be involved in the developmental mechanisms of steroid-resistant asthma.
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