title: Properdin and factor H production by human dendritic cells modulates their T-cell stimulatory capacity and is regulated by IFN-γ.
abstract: Dendritic cells (DCs) and complement are both key members of the innate and adaptive immune response. Recent experimental mouse models have shown that production of alternative pathway (AP) components by DCs strongly affects their ability to activate and regulate T-cell responses. In this study we investigated the production and regulation of properdin (fP) and factor H (fH) both integral regulators of the AP, by DCs and tolerogenic DCs (tolDCs). Both fP and fH were produced by DCs, with significantly higher levels of both AP components produced by tolDCs. Upon activation with IFN-γ both cells increased fH production, while simultaneously decreasing production of fP. IL-27, a member of the IL-12 family, increased fH, but production of fP remained unaffected. The functional capacity of fP and fH produced by DCs and tolDCs was confirmed by their ability to bind C3b. Inhibition of fH production by DCs resulted in a greater ability to induce allogenic CD4+T-cell proliferation. In contrast, inhibition of fP production led to a significantly reduced allostimulatory capacity. In summary, this study shows that production of fP and fH by DCs, differentially regulates their immunogenicity, and that the local cytokine environment can profoundly affect the production of fP and fH.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.|Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Karen O
authors.initials: KO
authors.lastname: Dixon
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.|Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: O'Flynn
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ngaisah
authors.initials: N
authors.lastname: Klar-Mohamad
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003179:Complement C3b / Q000378:metabolism; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism*; D003170:Complement Pathway, Alternative; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism; D064094:Interleukin-27 / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D011414:Properdin / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D064094:Interleukin-27; D007519:Isoantigens; D034741:RNA, Small Interfering; D011414:Properdin; D003179:Complement C3b; D017242:Complement Factor H; D007371:Interferon-gamma
keywords: Complement; Cytokines; Factor H; IFN-γ; IL-27; Properdin; Tolerogenic dendritic cells