Natural killer cells trigger differentiation of monocytes into dendritic cells

• Published in: Blood Vol. 110; no. 7; pp. 2484 - 2493
• Main Authors: Zhang, Angela L., Colmenero, Paula, Purath, Ulrich, Teixeira de Matos, Cristina, Hueber, Wolfgang, Klareskog, Lars, Tarner, Ingo H., Engleman, Edgar G., Söderström, Kalle
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.10.2007; The Americain Society of Hematology; American Society of Hematology
• Series: Immunobiology
• Subjects: Antigens - immunology; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Biological and medical sciences; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD40 Ligand - metabolism; CD56 Antigen - metabolism; Cell Differentiation; Cell Polarity; Cell Separation; Cell Shape; Cells, Cultured; Coculture Techniques; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Diseases of the osteoarticular system; Endocytosis; Fundamental and applied biological sciences. Psychology; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Humans; Immunobiology; Inflammation; Inflammatory joint diseases; Interleukin-15 - pharmacology; Killer Cells, Natural - cytology; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lymphocyte Activation; Medical sciences; Medicin och hälsovetenskap; Molecular and cellular biology; Monocytes - cytology; Phagocytes; Phenotype; Synovial Membrane - metabolism; Human; Dendritic cell; Skin disease; Immune response; Monocyte; Leukocyte; Cytokine; Diseases of the osteoarticular system; Cell cell interaction; Inflammatory joint disease; Cellular immunity; Cell differentiation; Inflammatory disease; Psoriatic arthritis; Spondylarthropathy; Natural killer cell; In vivo; Antigen presenting cell; Rheumatoid arthritis; T-Lymphocyte; Granulocyte macrophage colony stimulating factor; Growth factor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-02-076364

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−CD56bright) that accumulates in lymph nodes and chronically inflamed tissues triggers CD14+ monocytes to differentiate into potent T-helper-1 (TH1) 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 TH1-mediated inflammatory diseases such as RA by providing a local milieu for monocytes to differentiate into DC.