A unifying hypothesis for scleroderma: identifying a target cell for scleroderma

Curr Rheumatol Rep. 2011 Feb;13(1):28-36. doi: 10.1007/s11926-010-0152-8.


We propose that a recent change in the conception of the role of type 1 interferon and the identification of adventitial stem cells suggests a unifying hypothesis for scleroderma. This hypothesis begins with vasospasm. Vasospasm is fully reversible unless, as proposed here, the resulting ischemia leads to apoptosis and activation of type 1 interferon. The interferon, we propose, initiates immune amplification, including characteristic scleroderma-specific antibodies. We propose that the interferon also acts on adventitial stem cells, producing myofibroblasts, rarefaction, and intimal hyperplasia--three morphologic changes that characterize this disease. Regulator of G-protein signaling 5 (RGS5), a regulator of vasoactive G-protein-coupled receptors, is a cell type-specific marker of pericytes and scleroderma myofibroblasts. RGS5 may provide a key link between initial hyperplasia and fibrosis in this disease.

Publication types

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

MeSH terms

  • Fibrosis / immunology
  • Fibrosis / metabolism
  • Humans
  • Interferon Type I / immunology*
  • Interferon Type I / metabolism
  • RGS Proteins / immunology
  • RGS Proteins / metabolism
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / metabolism
  • Signal Transduction / immunology
  • Stem Cells / immunology
  • Stem Cells / metabolism
  • Vascular Diseases / immunology*
  • Vascular Diseases / metabolism


  • Interferon Type I
  • RGS Proteins