The airway epithelium in health and disease: "calm on the surface, paddling furiously underneath"

The airway epithelium, which is exposed to antigens and microbes throughout respiration, provides an enormous and delicate interface with the external environment. In major conducting airways the epithelium is covered by surface liquid, which includes an overlying mucous layer onto which inhaled particles are trapped. The physical defence mechanisms of the airway epithelium include the mucociliary escalator and complex structures known as tight junctions which control paracellular transport of inhaled material. In response to immunological challenge, epithelial cell surfaces produce antimicrobial chemicals (such as surfactants and defensins), cytokines (particularly type I and type III interferons) and chemokines following activation of their pattern recognition receptors, including Toll-like receptors (TLRs). This leads to recruitment of immune cells including dendritic cells, T cells and B cells. Given the speed, complexity and specificity of these responses, it is likely that, in an environment full of antigens such as the lung, epithelial surfaces will have developed mechanisms to inhibit inflammation, as has already been demonstrated for the microbe-rich milieu of the gut.1 Although it has been recognised for some time that the airway epithelium plays an important role in generating danger signals upon immunological challenge, we need to update these concepts to recognise the importance of this interface in protecting the host from unwanted responses to innocuous environmental agents. Data are now emerging which suggest that, in health, airway epithelial cells (AECs) play a critical role in regulating local immunological homeostasis. The study by Wang et al published in this issue of Thorax provides an important contribution to this body of evidence ( see page 283 ).2 The diverse array …