2.2. Non-T2high (T2low) asthma:
The mechanisms that contribute to pathogenesis of T2lowasthma are not yet clear but existing knowledge suggests that epithelium
may also play a role in these cases by the activation of IL-17 and IFN-γ
pathways. There is an imbalance between Th17/Treg cells which may play
an important role in steroid-resistant, severe neutrophilic asthma and
T2low asthma has been associated with the activation of
Th1 and/or Th17 cells [24].
Th17 cytokines play vital role in T2low disease with
increased levels of IL-17A and IL-17F in the bronchial walls of severe
asthmatics. This is associated with neutrophilic infiltration, airway
hyper-responsiveness (AHR), and steroid resistance. In mouse models,
blockade of T2 cytokines or corticosteroid treatment increased Th17
inflammation suggesting that treatment of T2high asthma
may allow the emergence of Th17high asthma [37].
Studies also show that IL-17 stimulates AECs to enhance MUC5AC
production.
At present, it is believed that enhanced IFN-γ expression is mainly
confined to severe asthma. Raundhal and colleagues [38] recently
reported that IFN-γ-induced downregulation of secretory leukocyte
protease inhibitor (SLPI) in AECs causes an increase in AHR in severe
asthma. Elevated IFN-γ is associated with high airway resistance,
increased inflammatory infiltration, and corticosteroid resistance
[24]. However, the specific mechanism(s) for these effects has not
yet been clarified.