Analysis of the regulatory function of natural killer cells from patients with systemic lupus erythematosus
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Natural killer (NK) cells participate in the regulation of the immune response. However, the immunomodulatory function of NK cells in systemic lupus erythematosus (SLE) is not well understood. The aim of this study was to evaluate the regulatory function of NK cells in SLE patients and to identify the NK cells involved in the pathogenesis of this complex disease. We analysed the expression of NK receptors and co-stimulatory molecules in peripheral NK cells (CD3–CD56 ) from SLE patients, as well as the numbers of human leucocyte antigen D-related (HLA-DR)/CD11c NK cells. In addition, NK cell regulatory function was assessed by the detection of NK cell-mediated dendritic cell (DC) lysis. We found that SLE patients showed increased numbers of immunoglobulin-like transcript 2 (ILT2) , CD86 and CD134 NK cells. Furthermore, NK cells from SLE patients induced higher levels of DC lysis. We were able to identify a new subset of NK cells co-expressing CD11c and HLA-DR. These atypical NK cells were increased in SLE patients when compared with controls. We have identified an expanded new subset of NK cells in SLE patients. This is the first study, to our knowledge, which demonstrates that NK cells in SLE patients have an altered phenotype with a high expression of receptors characteristic of dendritic cells. Our results suggest that the impairment in the regulatory function of NK cells, together with the increased number of DC-like NK cells, could play an important role in the development of SLE and highlight the importance of NK cells as a future therapeutic target. © 2017 British Society for Immunology
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Natural killer (NK) cells participate in the regulation of the immune response. However, the immunomodulatory function of NK cells in systemic lupus erythematosus (SLE) is not well understood. The aim of this study was to evaluate the regulatory function of NK cells in SLE patients and to identify the NK cells involved in the pathogenesis of this complex disease. We analysed the expression of NK receptors and co-stimulatory molecules in peripheral NK cells (CD3–CD56%2b) from SLE patients, as well as the numbers of human leucocyte antigen D-related (HLA-DR)/CD11c%2b NK cells. In addition, NK cell regulatory function was assessed by the detection of NK cell-mediated dendritic cell (DC) lysis. We found that SLE patients showed increased numbers of immunoglobulin-like transcript 2 (ILT2)%2b, CD86%2b and CD134%2b NK cells. Furthermore, NK cells from SLE patients induced higher levels of DC lysis. We were able to identify a new subset of NK cells co-expressing CD11c and HLA-DR. These atypical NK cells were increased in SLE patients when compared with controls. We have identified an expanded new subset of NK cells in SLE patients. This is the first study, to our knowledge, which demonstrates that NK cells in SLE patients have an altered phenotype with a high expression of receptors characteristic of dendritic cells. Our results suggest that the impairment in the regulatory function of NK cells, together with the increased number of DC-like NK cells, could play an important role in the development of SLE and highlight the importance of NK cells as a future therapeutic target. © 2017 British Society for Immunology
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atypical NK cell; dendritic cells; SLE CD134 antigen; CD3 antigen; CD56 antigen; CD86 antigen; gamma interferon; glycoprotein p 15095; HLA DR antigen; interleukin 10; interleukin 6; leukocyte immunoglobulin like receptor subfamily B member 1; natural cytotoxicity triggering receptor 3; natural killer cell receptor; natural killer cell receptor NKG2D; tumor necrosis factor; CD56 antigen; glycoprotein p 15095; HLA D antigen; HLA DR antigen; adaptive immunity; adult; antigen expression; Article; cell function; cell subpopulation; coculture; controlled study; cytolysis; dendritic cell; female; human; human cell; immunopathogenesis; immunoregulation; major clinical study; male; natural killer cell; phenotype; priority journal; protein expression; systemic lupus erythematosus; cell culture; cytotoxicity; dendritic cell; immunology; immunomodulation; immunophenotyping; lymphocyte subpopulation; metabolism; middle aged; natural killer cell; physiology; systemic lupus erythematosus; young adult; Adult; CD11c Antigen; CD56 Antigen; Cells, Cultured; Cytotoxicity, Immunologic; Dendritic Cells; Female; HLA-D Antigens; HLA-DR Antigens; Humans; Immunomodulation; Immunophenotyping; Killer Cells, Natural; Lupus Erythematosus, Systemic; Lymphocyte Subsets; Male; Middle Aged; Young Adult
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