Original Paper

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

  1. Frédérique Larousserie1,2,
  2. Stefan Pflanz3,†,
  3. Aurore Coulomb-L'Herminé4,
  4. Nicole Brousse2,
  5. Rob Kastelein3,
  6. Odile Devergne1,*

Article first published online: 19 JAN 2004

DOI: 10.1002/path.1508

Issue

The Journal of Pathology

The Journal of Pathology

Volume 202, Issue 2, pages 164–171, February 2004

Additional Information

How to Cite

Larousserie, F., Pflanz, S., Coulomb-L'Herminé, A., Brousse, N., Kastelein, R. and Devergne, O. (2004), Expression of IL-27 in human Th1-associated granulomatous diseases. J. Pathol., 202: 164–171. doi: 10.1002/path.1508

Author Information

  1. 1

    CNRS FRE 2444, Université Paris V, IFR Necker, Paris, France

  2. 2

    UPRES EA 219, Service d'Anatomie Pathologique, AP-HP, Hôpital Necker, Paris, France

  3. 3

    DNAX Research Institute, Palo Alto, USA

  4. 4

    Service d'Anatomie Pathologique, AP-HP, Hôpital Antoine Béclère, Clamart, France

  1. †

    Micromet AG, München, Germany.

*CNRS FRE 2444, Hôpital Necker, Bâtiment Sèvres, 161 Rue de Sèvres, 75015 Paris, France.

  • †

    Micromet AG, München, Germany.

Publication History

  1. Issue published online: 19 JAN 2004
  2. Article first published online: 19 JAN 2004
  3. Manuscript Accepted: 24 OCT 2003
  4. Manuscript Revised: 30 SEP 2003
  5. Manuscript Received: 6 AUG 2003

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Keywords:

  • cytokine;
  • IL-27;
  • sarcoidosis;
  • tuberculosis;
  • Crohn's disease;
  • Th1 response;
  • granuloma

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-γ (IFN-γ) 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. Copyright © 2004 John Wiley & Sons, Ltd.

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