Poly(I:C)-stimulated alveolar macrophages modulate extracellular matrix turnover and fibroblast activation through

Chen-Ni Chang1, Cheng-Fang Tsai2, Yen-Chang Chen1

  • 1Institute of Translational Medicine and New Drug Development, China Medical University, No.91 Hsueh-Shih Road, Taichung, 404333, Taiwan.

Abstract

Insights

Macrophages regulate lung fibrosis by secreting cystatin 6, which controls fibroblast activity via cathepsin B. This pathway offers insights into resolving fibrotic responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Pulmonary Medicine

Background:

  • Pulmonary fibrosis involves fibroblast activation and extracellular matrix deposition.
  • Macrophages are key in tissue repair but their role in modulating fibroblast phenotypes is unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms by which macrophages influence fibroblast behavior in pulmonary fibrosis.

Main Methods:

  • Alveolar macrophages were stimulated with poly(I:C) and their secretome analyzed.
  • Fibroblasts were exposed to macrophage conditioned medium (CM) to assess fibrogenic responses.

Main Results:

  • Poly(I:C)-stimulated macrophage CM reduced pro-fibrotic markers and fibroblast activation markers.
  • Macrophage CM induced cathepsin B in fibroblasts; its inhibition restored fibroblast activation.
  • Poly(I:C) reduced macrophage cystatin 6 secretion, impacting fibrogenesis.

Conclusions:

  • A novel macrophage cystatin 6-fibroblast cathepsin B axis regulates fibroblast behavior and fibrotic responses.
  • This pathway provides mechanistic insights into resolving fibrotic processes in the lung.

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