title: Natural killer cells trigger differentiation of monocytes into dendritic cells.
abstract: Circulating monocytes can differentiate into dendritic cells (moDCs), which are potent inducers of adaptive immune responses. Previous reports show that granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 induce monocyte differentiation into moDCs in vitro, but little is known about the physiological requirements that initiate moDC differentiation in vivo. Here we show that a unique natural killer (NK) cell subset (CD3(-)CD56(bright)) that accumulates in lymph nodes and chronically inflamed tissues triggers CD14(+) monocytes to differentiate into potent T-helper-1 (T(H)1) promoting DC. This process requires direct contact of monocytes with NK cells and is mediated by GM-CSF and CD154 derived from NK cells. It is noteworthy that synovial fluid (SF) from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), but not osteoarthritis (OA), induces monocytes to differentiate into DC. However, this process occurs only in the presence of NK cells. We propose that NK cells play a role in the maintenance of T(H)1-mediated inflammatory diseases such as RA by providing a local milieu for monocytes to differentiate into DC.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Palo Alto, CA 94304-1204, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Zhang
authors.forename: Paula
authors.initials: P
authors.lastname: Colmenero
authors.forename: Ulrich
authors.initials: U
authors.lastname: Purath
authors.forename: Cristina
authors.initials: C
authors.lastname: Teixeira de Matos
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hueber
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Ingo H
authors.initials: IH
authors.lastname: Tarner
authors.forename: Edgar G
authors.initials: EG
authors.lastname: Engleman
authors.forename: Kalle
authors.initials: K
authors.lastname: Söderström
mesh_terms: D000941:Antigens / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D023201:CD40 Ligand / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D016764:Cell Polarity; D002469:Cell Separation; D048430:Cell Shape; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology*; D010586:Phagocytes; D010641:Phenotype; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: D000941:Antigens; D019002:CD56 Antigen; D019409:Interleukin-15; D023201:CD40 Ligand; D016178:Granulocyte-Macrophage Colony-Stimulating Factor