title: Expression of IL-27 in human Th1-associated granulomatous diseases.
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.
authors.affiliation: CNRS FRE 2444, Université Paris V, IFR Necker, Paris, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Larousserie
authors.forename: Stefan
authors.initials: S
authors.lastname: Pflanz
authors.forename: Aurore
authors.initials: A
authors.lastname: Coulomb-L'Herminé
authors.forename: Nicole
authors.initials: N
authors.lastname: Brousse
authors.forename: Rob
authors.initials: R
authors.lastname: Kastelein
authors.forename: Odile
authors.initials: O
authors.lastname: Devergne
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D003424:Crohn Disease / Q000276:immunology; D005982:Glutathione Transferase / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006099:Granuloma / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007378:Interleukins / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D015778:Minor Histocompatibility Antigens; D021122:Protein Subunits / Q000378:metabolism; D018121:Receptors, Cytokine; D012507:Sarcoidosis / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology
chemical_list: D002352:Carrier Proteins; C097732:EBI3 protein, human; D006023:Glycoproteins; C117709:Gsto1 protein, mouse; C486767:Il27 protein, mouse; D007378:Interleukins; C464565:MYDGF protein, human; D015778:Minor Histocompatibility Antigens; D021122:Protein Subunits; D018121:Receptors, Cytokine; D005982:Glutathione Transferase