Background: Airway accumulation of eosinophils and bronchial hyperresponsiveness (BHR) are prominent features of bronchial asthma, though the contribution of eosinophils to the development of BHR is controversial. Similar to Th2 cell-mediated pathology, Th9 cells, characterized by IL-9-producing activity, have been demonstrated to induce airway eosinophilia and BHR. In this study, we investigated the role of eosinophils in Th9-mediated BHR by employing Th9 cell-transferred murine airway inflammation model.
Methods: Ovalbumin (OVA)-specific Th2 and Th9 cells were differentiated from CD4(+) T cells of DO11.10/RAG-2(-/-) mice in vitro and cytokine-producing activity of those cells was examined. BALB/c mice were adoptively transferred with Th2 or Th9 cells and challenged with OVA. Then, the number of inflammatory cells in bronchoalveolar lavage fluid and bronchial responsiveness to inhaled methacholine were determined.
Results: Both in Th2 and Th9 cell-transferred mice, substantial accumulation of eosinophils in the lungs and BHR were induced by challenge with specific antigen. Nevertheless, an essential and dispensable role of eosinophils in Th2- and Th9-mediated BHR, respectively, was demonstrated by employing eosinophil-deficient mice. The neutralization of IL-9 as well as deficiency of IL-10 in the donor cells did not affect Th9-mediated BHR.
Conclusions: In contrast to Th2-mediated and eosinophil-dependent BHR, Th9 could induce BHR independently from eosinophils and its characteristic cytokines, IL-9 and IL-10.
Keywords: Bronchial asthma; Bronchial hyperresponsiveness; Eosinophil; Eosinophil-deficient mice; Th9 cells.
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