Role of IL17 A/F in experimental lung fibrosis

Abstract

The Interleukin 17 family of cytokines includes six members, IL-17A-IL17F. IL-17A and F bind to the same receptor and share considerable degree of homology. IL-17 has been implicated in neutrophil-dependent antibacterial immunity as well as chronic inflammatory diseases. However, its role in lung fibrosis is still controversial. In the current study, we examined the role of IL17A/F double KO (dKO) in two models of adenoviral TGF-β1 or bleomycin (BLM)-induced experimental lung fibrosis in mice. AdTGF-β1 treatment increased lung collagen contents in WT and IL17A/F dKO mice with no significant differences between groups. However, BLM challenge triggered a distinct angiocentric neutrophilic infiltration of the lung parenchyma in IL-17AF dKO mice but not WT mice within six days of treatment, which was accompanied by profound endothelial cell activation and drastically reduced survival. At the same time, numbers of CD4+, CD8+ and regulatory T cells were significantly decreased in IL-17AF dKO as compared to WT mice. Experiments in bone marrow chimeras revealed that such predominant neutrophilic mobilization was independent of IL-17AF derived from the hematopoietic system. Collectively, the data demonstrate a limited role for IL-17AF in experimental fibrosis, but identify a critical role for IL-17AF in the regulation of neutrophil-driven lung inflammation in the early phase of BLM challenge.