IL-17 in the lung: the good, the bad, and the ugly

Abstract

The IL-17 family of cytokines has emerged over the last two decades as a pleiotropic group of molecules that function in a wide variety of both beneficial and detrimental (pathological) processes, mainly in mucosal barrier tissue. The beneficial effects of IL-17 expression are especially important in the lung, where exposure to foreign agents is abundant. IL-17A plays an important role in protection from both extracellular bacteria and fungi, as well as viruses that infect cells of the mucosal tracts. IL-17 coregulated cytokines, such as IL-22, are involved in maintaining epithelial cell homeostasis and participate in epithelial cell repair/regeneration following inflammatory insults. Thus, the IL-17/IL-22 axis is important in both responding to, and recovering from, pathogens. However, aberrant expression or overexpression of IL-17 cytokines contributes to a number of pathological outcomes, including asthma, pneumonitis, and generation or exacerbation of pulmonary fibrosis. This review covers the good, bad, and ugly aspects of IL-17 in the lung.

Keywords: IL-17; IL-22; asthma; fibrosis; neutrophils.

Fig. 1.

The IL-17 family and IL-17-related cytokines have a variety of beneficial and detrimental effects in the lung. Top, blue panel: IL-17A and IL-17C serve beneficial effects in the lung and aid in the recruitment of neutrophils to clear extracellular pathogens (21, 51, 118). IL-22 also serves a protective role in the lung and induces autophagy in epithelial cells, reducing inflammation and promoting epithelial repair following pathogen damage (47, 65, 85). Of course, prolonged neutrophil accumulation can also lead to tissue damage. Bottom, red panel: IL-17A has detrimental effects during exacerbations of asthma, COPD, and pulmonary fibrosis by promoting eosinophil recruitment/activation leading to the secretion of profibrotic mediators such as TGF-β (2). IL-17A can act directly on both epithelial cells and fibroblasts, promoting epithelial to mesenchymal transition, as well as myofibroblast differentiation and extracellular matrix production, resulting in fibrosis (84, 134). Furthermore, IL-17A can stimulate epithelial cells to upregulate mucus-producing gene products, which can exacerbate asthma (123).