Convergence of air pollutant-induced redox-sensitive signals in the dendritic cells contributes to asthma pathogenesis.

Exposure to airborne particulate matter (PM) is a major risk factor for allergic airway inflammation such as asthma. Many of the PM components (i.e., polycyclic aromatic hydrocarbons and metals) are redox-active and capable of inducing cellular oxidative stress and injuries including inflammation and cell death. Airway epithelial cells and antigen-presenting dendritic cells (DC) are the major and direct targets of inhaled PM. The epithelial cells can further enhance the DC response to allergen and PM through several immune regulatory cytokines including thymic stromal lymphopoietin (TSLP), IL-33, and IL-25. Among these cytokines TSLP is particularly relevant to the mechanisms by which particulate air pollutants contribute to asthma pathogenesis. Studies have found that TSLP released by PM-exposed human airway epithelial cells could polarize the DC towards a T-helper 2 immune response, which is one of the key immunological mechanisms in asthma pathogenesis. The convergence of regulatory signals generated by PM-induced oxidative stress in DC and the interactions among them may be one of the major mechanisms that are specifically related to the contribution of PM towards asthma pathogenesis.