Regulation of mucosal immunity by airway epithelium: The interleukin-17A paradigm

Increasing evidence suggests that the airway epithelium plays an essential role in the modulation of airway innate and adaptive immune responses in addition to serving as a physical barrier against microbial infection and exterior insults. The nature of this modulation and the potential mediators involved are currently unresolved. Interleukin (IL)-17A has recently emerged as a potential candidate for directly modulating innate and adaptive immune responses. Our laboratory has recently shown that IL-17A is one of the most potent cytokines among a panel of 21 (IL-1α, -1β, -2-13, -15, -16, and -18, interferon-γ, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-α) for stimulating the expression of human β-defensin (HBD)-2 and CC chemokine ligand 20 (CCL20)/macrophage inflammatory protein-3 by primary human airway epithelial cells. Using Affymetrix gene chips and quantitative polymerase chain reaction, we identified the following IL-17A-induced genes in well-differentiated normal human bronchial epithelium: IL-19, growth-related oncogene-α, -β, and -γ, CXC-5, and glutamate carboxypeptidase-2, in addition to the known inducible cytokines CCL20, IL-8, and HBD-2. As the presence of IL-17A at elevated levels has been demonstrated in a variety of airway diseases, including those related to microbial infection, chronic obstructive pulmonary disease, and Th2-dominated diseases, the induction of these diverse cytokines may further support the critical role of IL-17A in the pathogenesis of airway diseases and airway inflammation.