GM-CSF as crucial rheostat of the allergic airways

Asthma is a heterogeneous respiratory disease in which many immune and structural lung cells act in concert to amplify local inflammatory processes and cause airway remodeling resulting in clinical symptoms and chronic disease. Upon allergen-induced activation of airway epithelial (EP) cells, there is early production of IL-1α that subsequently acts on the IL-1R in an autocrine manner to boost further production of cytokines like GM-CSF, TSLP, IL-33 and IL-25. GM-CSF has been shown to be a key factor in the induction of Th2 responses leading to asthma and increased production of GM-CSF has been observed in asthmatic patients. Conversely, farm dust-mediated asthma prevention went along with a dramatic reduction in EP-derived GM-CSF. Therefore, we hypothesize that GM-CSF is a crucial rheostat in the induction of allergic immune responses. However, although many cells have been shown to produce and respond to GM-CSF, the relative distribution and contribution of GM-CSF producing and responding cells in the context of allergic asthma is still unclear. Therefore, we will use novel mouse models to study GM-CSF function in vivo. Given the importance of GM-CSF in allergic asthma, these insights might aid the development of targeted therapies against allergic asthma.