Expression of IL-27 in human Th1-associated granulomatous diseases

J Pathol. 2004 Feb;202(2):164-71. doi: 10.1002/path.1508.

Abstract

Interleukin (IL)-27 is a newly described member of the IL-12 family. It is a heterodimeric cytokine composed of two subunits, p28 and Epstein-Barr virus-induced gene 3 (EBI3). In vitro studies have shown that IL-27 is mainly produced by activated monocytes and dendritic cells. It induces the proliferation of naïve CD4-positive T cells and synergizes with IL-12 for interferon-gamma (IFN-gamma) production. Knock-out mice for the IL-27 receptor (WSX-1/TCCR) have impaired Th1 responses and form abnormal granulomas when injected with bacillus Calmette-Guérin. However, the expression profile of IL-27 in vivo is currently unknown. To investigate the potential role of IL-27 in the development of a Th1 response in humans in vivo, this study has analysed the in situ expression of IL-27 subunits in three types of granulomatous disease (tuberculosis, sarcoidosis, and Crohn's disease), each characterized by a Th1 response. Tissue sections from patients with tuberculosis (n = 9), sarcoidosis (n = 8), or Crohn's disease (n = 7) were analysed by immunohistochemistry with anti-EBI3 and anti-p28 antibodies, in parallel with control tissues (control reactive lymph nodes, n = 14, and control intestinal tissues, n = 11). In granulomatous tissues, EBI3 and p28 co-expression was detected in epithelioid and multinucleate giant cells in granulomas. In addition, sinus or tissue macrophages, endothelial cells, and plasma cells were found to co-express EBI3 and p28. These data support a possible role for IL-27 in human Th1 responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / metabolism
  • Crohn Disease / immunology
  • Glutathione Transferase / metabolism
  • Glycoproteins / metabolism
  • Granuloma / immunology*
  • Humans
  • Immunoenzyme Techniques
  • Interleukins / metabolism*
  • Lymph Nodes / immunology
  • Minor Histocompatibility Antigens
  • Protein Subunits / metabolism
  • Receptors, Cytokine*
  • Sarcoidosis / immunology
  • Th1 Cells / immunology*
  • Tuberculosis / immunology

Substances

  • Carrier Proteins
  • EBI3 protein, human
  • Glycoproteins
  • Gsto1 protein, mouse
  • Il27 protein, mouse
  • Interleukins
  • MYDGF protein, human
  • Minor Histocompatibility Antigens
  • Protein Subunits
  • Receptors, Cytokine
  • Glutathione Transferase