Innate T-cell-derived IL-17A/F protects from bleomycin-induced acute lung injury but not bleomycin or adenoviral TGF-β1-induced lung fibrosis in mice.

Abstract

The pathobiology of IL-17 in lung fibrogenesis is controversial. Here we examined the role of IL-17A/F in bleomycin (BLM) and adenoviral TGF-β1-induced lung fibrosis in mice. In both experimental models, WT and IL17af^-/- mice showed increased collagen contents and remodeled lung architecture as assessed by histopathological examination, suggesting that IL-17A/F is dispensable for lung fibrogenesis. However, IL17af^-/- mice responded to the BLM challenge with perturbed lung leukocyte subset recruitment. More specifically, bleomycin triggered angiocentric neutrophilic infiltrations of the lung accompanied by increased mortality of IL17af^-/- but not WT mice. WT bone marrow transplantation failed to correct this phenotype in BLM-challenged IL17af^-/- mice. Conversely, IL17a/f^-/- bone marrow transplantation → WT did not perturb lung leukocytic responses upon BLM. At the same time, IL17af^-/- mice treated with recombinant IL-17A/F showed an attenuated lung inflammatory response to BLM. Together, the data show that the degree of BLM-driven acute lung injury was critically dependent on the presence of IL-17A/F, while in both models, the fibrotic remodeling process was not.