Oxidation alters IL-33 function: new insights in the biology of different forms of IL-33 and their relevance for COPD

Extract

In recent decades, the perception of the epithelium lining the airways has drastically changed from that of a physical barrier that mediates mucociliary transport to a multifunctional tissue that is actively involved in initiating and regulating tissue inflammation and remodelling [1, 2]. The airway epithelium produces a range of mediators, including chemokines, cytokines, growth factors and lipid mediators, to mediate these effects. Among these, the alarmin cytokines interleukin (IL)-33, thymic stromal lymphopoietin (TSLP) and IL-25 were found to regulate type 2 responses through effects on immune cells such as T helper type 2 (Th2) lymphocytes and type 2 innate lymphocytes (ILC2) [3]. Epithelial cells were recognised as source of these alarmin cytokines following exposure to a range of (environmental) triggers, including respiratory viruses, parasites, air pollutants and cigarette smoke, as well as allergens. These insults all have in common that they provoke a danger signal to the immune system upon damaging the epithelial layer. Based on their role in directing immune responses, alarmin cytokines have attracted attention as targets for a novel set of biologicals in the treatment of inflammatory lung diseases. Promising results were reported from clinical studies in which TSLP and IL-33 were targeted for the treatment of exacerbations of asthma and COPD [4].