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

Eur J Immunol. 2024 Dec;54(12):e2451323. doi: 10.1002/eji.202451323. Epub 2024 Sep 5.

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.

Keywords: Fibrosis; IL‐17; Injury; Lung; Th17; γδ T cells.

MeSH terms

  • Acute Lung Injury* / chemically induced
  • Acute Lung Injury* / immunology
  • Acute Lung Injury* / pathology
  • Adenoviridae / genetics
  • Animals
  • Bleomycin*
  • Disease Models, Animal
  • Immunity, Innate
  • Interleukin-17* / genetics
  • Interleukin-17* / metabolism
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout*
  • Pulmonary Fibrosis* / chemically induced
  • Pulmonary Fibrosis* / immunology
  • Transforming Growth Factor beta1* / metabolism

Substances

  • Bleomycin
  • Interleukin-17
  • Transforming Growth Factor beta1
  • Il17a protein, mouse
  • Il17f protein, mouse