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

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.

• Moog, M. T.
• Baltes, M.
• Röpke, T.
• Aschenbrenner, F.
• Maus, R.
• Stolper, J.
• Jonigk, D.
• Prinz, I.
• Kolb, M.
• Maus, U. A.