Can airway tolerance be promoted immunopharmacologically with Aspirin in Aspirin-insensitive allergic bronchial asthmatics by T regulatory cells (Tregs)-directed immunoregulatory therapy?

Abstract

The pathobiology of allergic bronchial asthma is mediated by over-expressed T helper type 2 (Th2)-biased immune responses to harmless environmental antigens, leading to airway inflammation and hyper-responsiveness. These Th2 responses are normally suppressed by functional T regulatory cells (Tregs), which maintain the airway tolerance. However, the Tregs activity is conceived to be compromised in allergic asthmatics. The curative therapy to counteract this immune dysregulation is not available so far, and to devise such a remedy is the current research impetus in allergic asthma therapeutics. One of the novel insights is to consider a Tregs-directed immunoregulatory therapy that could harness endogenous Tregs to redress the Th2/Tregs imbalance, thus enhancing the airway tolerance. Aspirin or acetylsalicylic acid (ASA) is a prototype non-steroidal anti-inflammatory drug that possesses intriguing immunopharmacological attributes. For example, it can enhance the number or the frequency of functional Tregs, especially natural CD4⁺ CD25⁺ FoxP3⁺ Tregs, either directly or by inducing tolerogenic activity in dendritic cells (DCs). It is also considered to be beneficial for the induction of immunological tolerance in autoimmunity and graft rejection. This raises the question whether ASA, if exploited optimally, may be used to induce and harness endogenous Tregs activity for redressing Th2/Tregs imbalance in allergic asthma. In this paper, we hypothesise that ASA may help to counteract the underlying immune dysregulation in allergic asthma by promoting airway tolerance. Nevertheless, the future research in this regard will selectively need to be targeted to allergic asthma models, which are ASA insensitive, as ASA has some adverse background and is contraindicated in asthmatics who are sensitive to it.