title: IL-27 renders DC immunosuppressive by induction of B7-H1.
abstract: IL-27, an IL-12 family member, was initially described as a proinflammatory cytokine. Nevertheless, it also poses anti-inflammatory activity, being involved in suppressing development of TH-17 cells as well as in the induction of inhibitory Tr1 cells. Recent data obtained in mice suggest that it can down-modulate the function of APCs. However, until now, nothing was known about the influence of IL-27 on human DCs. We investigated the effect of IL-27 on in vitro human MoDCs and on ex vivo blood DCs. Our results show that treatment of mDCs with IL-27 led to specific up-regulation of surface expression of several molecules, including B7-H1, in the absence of general DC maturation. Moreover, we demonstrated that IL-27-treated DCs exhibit a reduced capacity to stimulate proliferation and cytokine production of allogeneic T cells as compared with control DCs. Decisively, we identified B7-H1 as a crucial molecule, responsible for suppressive effects of "IL-27 DC" on T cells. Our data demonstrate for the first time that in addition to the dual role of IL-27 in the modulation of T cell activation and differentiation, human IL-27 modulates an immune response through DCs, i.e., by inducing immunosuppressive B7-H1 molecules and reducing the stimulatory potential of DCs.
authors.affiliation: Department of Dermatology, University of Heidelberg, Im Neuenheimer Feld 350, Heidelberg, Germany. svetlana.karakhanova@med.uni-heidelberg.de
authors.forename: Svetlana
authors.initials: S
authors.lastname: Karakhanova
authors.forename: Tanja
authors.initials: T
authors.lastname: Bedke
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Enk
authors.forename: Karsten
authors.initials: K
authors.lastname: Mahnke
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D060890:B7-H1 Antigen; D015153:Blotting, Western; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation; D050794:STAT1 Transcription Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D007378:Interleukins; C464565:MYDGF protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D007371:Interferon-gamma