2017 年 64 巻 3 号 p. 45-55
Summary: Asthma is an allergic disease characterized by chronic airway inflammation, airway hyperresponsiveness (AHR), reversibility and remodeling. Inhaled corticosteroids (ICS) are effective in many patients with asthma. However, ICS are a controlling, but not but curative treatment, and there are still many patients with refractory and difficult-to-treat asthma. The evaluation of airway inflammation by induced sputum, non-specific AHR by methacholine, and asthmatic reactions by specific allergen challenge techniques are useful not only to investigate the pathogenesis of asthma but also to help develop new drugs for asthma management. Interactions between inflammation and regulation, such as between regulatory T cells (Tregs), and AHR were investigated using these techniques. The phenotypes are Tregs characterized by expression of the forkhead box P3 (Foxp3) and cytotoxic T-lymphocyte antigen 4 (CTLA4), which are potent mediators of dominant self-tolerance. Foxp3 and CTLA4 interact with each other. In patients with mild asthma, airway Tregs were decreased and airway eosinophilic inflammation was activated with accelerated AHR. Human asthmatic attack models by allergen challenge demonstrated that airway Tregs were decreased from the baseline with late asthmatic response (LAR) in patients with dual-responder asthma, and there was a significant correlation between change in airway Tregs and LAR. Airway Tregs were increased with escalation of interleukin-10 by ICS. The investigation of Tregs may lead to new strategies for management of asthma and other allergic diseases.
