title: IL-36α induces maturation of Th1-inducing human MDDC and synergises with IFN-γ to induce high surface expression of CD14 and CD11c.
abstract: We show that IL-36α induced maturation of human MDDCs and stimulated differentiation of IFN-γ producing (Type 1) CD3+ lymphocytes but was not as effective as IL-36β in doing so. For the first time, we also show that IL-36α induced expression of CD14 by MDDCs and this was highly potentiated by co-cultured with IFN-γ. In contrast, lipopolysaccharide (LPS) did not increase CD14 expression by MDDCs, suggesting that if MDDCs represent a physiologically relevant population in vivo, they need to be stimulated by relevant inflammatory cytokines prior to CD14 expression and detection of LPS, expressed by Gram negative bacteria. IFN-γ synergised with IL-36α to restore the high levels of CD11c expression by MDDCs, which was reduced by culture with these cytokines in isolation. IL-36α/IFN-γ synergy also correlated with increased binding of the opsonic complement protein (iC3b) to MDDCs. However although IL-36α increased the phagocytic capacity of MDDCs for Salmonella Typhimurium 4/74 this was not synergistically increased by IFN-γ (P>0.05). In conclusion we report the hitherto unknown effects of IL-36α on the innate cell function of human MDDCs.
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, UK.
authors.forename: John
authors.initials: J
authors.lastname: Higgins
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, UK.
authors.forename: Shilla
authors.initials: S
authors.lastname: Mutamba
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Nottingham, UK.
authors.forename: Yashwant
authors.initials: Y
authors.lastname: Mahida
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Barrow
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, UK. Electronic address: n.foster@nottingham.ac.uk.
authors.forename: Neil
authors.initials: N
authors.lastname: Foster
mesh_terms: D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003179:Complement C3b / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology* / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D011485:Protein Binding; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D039521:CD11c Antigen; D007375:Interleukin-1; D018950:Lipopolysaccharide Receptors; C572887:interleukin 36, human; D003179:Complement C3b; D007371:Interferon-gamma
keywords: CD209; Dendritic cell; IFN-γ; IL-36R; IL-36α