Pulmonary fibrosis and type-17 immunity

Respir Investig. 2023 Sep;61(5):553-562. doi: 10.1016/j.resinv.2023.05.005. Epub 2023 Jun 23.

Abstract

Fibrosis of the lung can occur in idiopathic pulmonary fibrosis, collagen vascular diseases, and hypersensitivity pneumonitis, among other diseases. Transforming growth factor (TGF)-β, vascular epithelial growth factor, fibroblast growth factor, and platelet-derived growth factor contribute to the pathophysiology of fibrosis. TGF-β and other cytokines, including interleukin (IL)-1β, IL-6, and IL-23, activate type-17 immunity, which is involved in pulmonary fibrosis. The components of type-17 immunity include type-17 helper T cells, γδT cells, IL-17A-producing CD8-positive T cells, invariant NKT cells, and group 3 innate lymphoid cells. IL-17A, the main cytokine of type-17 immunity, is able to induce the epithelial-mesenchymal transition in epithelial cells via a production of TGF-β, directly stimulate fibroblasts and fibrocytes, and inhibit autophagy, which otherwise protects against pulmonary fibrosis. IL-23 induces type-17 immunity and plays an important role in the acute exacerbation of pulmonary fibrosis. Clinical studies have also linked type-17 immunity to the pathogenesis of pulmonary fibrosis. Consequently, targeting type-17 immunity may serve as a new therapeutic strategy to prevent the development or exacerbation of pulmonary fibrosis.

Keywords: IL-17; IL-23; Idiopathic pulmonary fibrosis; Interstitial lung disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Bleomycin / metabolism
  • Bleomycin / therapeutic use
  • Cytokines / metabolism
  • Fibrosis
  • Humans
  • Idiopathic Pulmonary Fibrosis* / drug therapy
  • Idiopathic Pulmonary Fibrosis* / etiology
  • Immunity, Innate
  • Interleukin-17* / metabolism
  • Interleukin-17* / therapeutic use
  • Interleukin-23 / metabolism
  • Interleukin-23 / therapeutic use
  • Lung / pathology
  • Lymphocytes
  • Mice
  • Mice, Inbred C57BL
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / therapeutic use
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta1 / therapeutic use

Substances

  • Interleukin-17
  • Cytokines
  • Transforming Growth Factor beta
  • Interleukin-23
  • Bleomycin
  • Transforming Growth Factor beta1