Media type: E-Article Title: Expression of IL‐27 in human Th1‐associated granulomatous diseases Contributor: Larousserie, Frédérique; Pflanz, Stefan; Coulomb‐L'Herminé, Aurore; Brousse, Nicole; Kastelein, Rob; Devergne, Odile imprint: Wiley, 2004 Published in: The Journal of Pathology Language: English DOI: 10.1002/path.1508 ISSN: 0022-3417; 1096-9896 Keywords: Pathology and Forensic Medicine Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:p>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). <jats:italic>In vitro</jats:italic> 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 <jats:italic>in vivo</jats:italic> is currently unknown. To investigate the potential role of IL‐27 in the development of a Th1 response in humans <jats:italic>in vivo</jats:italic>, this study has analysed the <jats:italic>in situ</jats:italic> 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 (<jats:italic>n</jats:italic> = 9), sarcoidosis (<jats:italic>n</jats:italic> = 8), or Crohn's disease (<jats:italic>n</jats:italic> = 7) were analysed by immunohistochemistry with anti‐EBI3 and anti‐p28 antibodies, in parallel with control tissues (control reactive lymph nodes, <jats:italic>n</jats:italic> = 14, and control intestinal tissues, <jats:italic>n</jats:italic> = 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.</jats:p>