IL-7 inhibits fibroblast TGF-beta production and signaling in pulmonary fibrosis

J Clin Invest. 2002 Apr;109(7):931-7. doi: 10.1172/JCI14685.


Based on studies by our group and others, we hypothesized that IL-7 may possess antifibrotic activities in an IFN-gamma-dependent and independent manner. Here, we have evaluated the antifibrotic therapeutic potential of IL-7 in both in vitro and in vivo pulmonary fibrosis models. IL-7 inhibited both TGF-beta production and signaling in fibroblasts and required an intact JAK1/STAT1 signal transduction pathway. IL-7-mediated inhibition of TGF-beta signaling was found to be associated with an increase in Smad7, a major inhibitory regulator in the SMAD family. In the presence of IL-7, Smad7 dominant negative fibroblasts restored TGF-beta-induced collagen synthesis, indicating that an IL-7-mediated increase in Smad7 suppressed TGF-beta signaling. Consistent with these in vitro findings, recombinant IL-7 decreased bleomycin-induced pulmonary fibrosis in vivo, independent of IFN-gamma. The antifibrotic activities of IL-7 merit further basic and clinical investigation for the treatment of pulmonary fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bleomycin / adverse effects
  • Cells, Cultured
  • Collagen / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / immunology
  • Gene Expression
  • Humans
  • Interleukin-7 / immunology*
  • Interleukin-7 / pharmacology
  • Janus Kinase 1
  • Mice
  • Mice, Inbred C57BL
  • Mice, SCID
  • Protein-Tyrosine Kinases / immunology
  • Pulmonary Fibrosis / immunology*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • STAT1 Transcription Factor
  • Signal Transduction / immunology*
  • Smad7 Protein
  • Trans-Activators / genetics
  • Trans-Activators / immunology
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta2
  • Transforming Growth Factor beta3


  • DNA-Binding Proteins
  • Interleukin-7
  • Recombinant Proteins
  • SMAD7 protein, human
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Smad7 Protein
  • Smad7 protein, mouse
  • Stat1 protein, mouse
  • TGFB1 protein, human
  • TGFB2 protein, human
  • Tgfb1 protein, mouse
  • Tgfb3 protein, mouse
  • Trans-Activators
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta2
  • Transforming Growth Factor beta3
  • Bleomycin
  • Collagen
  • Protein-Tyrosine Kinases
  • JAK1 protein, human
  • Jak1 protein, mouse
  • Janus Kinase 1