Potential Mechanisms of T Cell-Mediated and Eosinophil-Independent Bronchial Hyperresponsiveness

Abstract

Bronchial asthma is a chronic disease characterized by reversible airway obstruction, mucus production, and bronchial hyperresponsiveness (BHR). Although Th2 cell-mediated eosinophilic inflammation is an important disease mechanism in the majority of patients with bronchial asthma, recent studies suggest the possible development of Th2-independent airway inflammation and BHR. These non-Th2 endotype patients seem to consist of multiple subgroups, and often do not respond to inhaled corticosteroids. Therefore, to understand the pathogenesis of asthma, it is important to characterize these non-Th2 subgroups. Recently, we demonstrated that Th9 cells induce eosinophil infiltration and eosinophil-independent BHR, and Th9 cells-mediated BHR may be resistant to glucocorticoid. In this review, we summarize the contribution of several T cell subsets in the development of bronchial asthma and introduce our recent study demonstrating Th9 cell-mediated and eosinophil-independent BHR.

Keywords: airway inflammation; allergy; asthma; bronchial hyper responsiveness.

Figure 1

Schematic mechanisms of eosinophil-independent and steroid-resistant bronchial hyperresponsiveness (BHR) mediated by Th9 cells compared with Th2-mediated responses.

Figure 2

Antigen-induced airway inflammation in Th2 and Th9 cell-transferred mice. Th2 (A) or Th9 (B) cell-transferred wild-type (WT) and eosinophil-deficient ΔdblGATA mice were challenged with ovalbumin (OVA) or saline. Seventy-two hours after the challenge, bronchial responsiveness to inhaled methacholine (MCh) was assessed. Data are expressed as mean ± SEM of 3–10 animals. * p < 0.05 compared with saline-challenged WT mice. (Reference [38], modified).

Figure 3

Dexamethsone (Dex) did not attenuate Th9 cell-mediated airway inflammation. Th2 (A) or Th9 (B) cell-transferred mice were challenged with ovalbumin (OVA) or saline. Mice were treated with either Dex (5 mg/kg) or phosphate buffered saline (PBS) as a control twice, at 1 h before and at 24 h after the OVA challenge, by subcutaneous injection. Seventy-two hours after the challenge, the bronchial responsiveness to inhaled MCh was assessed. Data are expressed as mean ± SEM of 5–7 animals. * p < 0.05, compared with OVA-challenged mice. (Reference [133], modified).