Interleukin (IL)-4, IL-13, and IL-17A differentially affect the profibrotic and proinflammatory functions of fibrocytes from asthmatic patients

Mucosal Immunol. 2012 Mar;5(2):140-9. doi: 10.1038/mi.2011.60. Epub 2011 Dec 21.

Abstract

Fibrocytes contribute to the fibrotic changes most frequently observed in forms of asthma where inflammation is driven by T helper type 2 (Th2) cells. The mechanisms that regulate the profibrotic function of asthmatic fibrocytes are largely unknown. We isolated circulating fibrocytes from patients with allergen-exacerbated asthma, who showed the presence of fibrocytes, together with elevated concentrations of interleukin (IL)-4 and IL-13 and slightly increased concentrations of the Th17 cell-derived IL-17A, in induced sputum. Fibrocytes stimulated with IL-4 and IL-13 produced high levels of collagenous and non-collagenous matrix components and low levels of proinflammatory cytokines. Conversely, fibrocytes stimulated with IL-17A proliferated and released proinflammatory factors that may promote neutrophil recruitment and airway hyperresponsiveness. IL-17A also indirectly increased α-smooth muscle actin but not collagen expression in fibrocytes. Thus, fibrocytes may proliferate and express a predominant profibrotic or proinflammatory phenotype in asthmatic airways depending on the local concentrations of Th2- and Th17-derived cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Airway Remodeling / drug effects
  • Asthma / complications
  • Asthma / immunology*
  • Asthma / therapy
  • Bronchial Hyperreactivity / etiology
  • Bronchial Hyperreactivity / immunology*
  • Bronchial Hyperreactivity / therapy
  • Cell Proliferation
  • Cells, Cultured
  • Collagen / genetics
  • Collagen / metabolism
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / immunology
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Humans
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Interleukin-13 / analysis
  • Interleukin-13 / pharmacology
  • Interleukin-17 / analysis
  • Interleukin-17 / pharmacology
  • Interleukin-4 / analysis
  • Interleukin-4 / pharmacology
  • Male
  • Pulmonary Fibrosis / etiology
  • Pulmonary Fibrosis / immunology*
  • Pulmonary Fibrosis / therapy
  • Sputum / chemistry
  • Young Adult

Substances

  • Inflammation Mediators
  • Interleukin-13
  • Interleukin-17
  • Interleukin-4
  • Collagen