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    A novel role of IL-17 producing lymphocytes in mediating lytic bone disease in multiple myeloma

    Blood. 2010 Jul 27. [Epub ahead of print]

    This paper demonstrates that IL-17-producing marrow infiltration lymphocytes (MIL) from myeloma bone marrow have an IL-17 phenotype, which enhances osteoclast activation.

    Authors: Noonan K, Marchionni L, Anderson J, et. al

    Osteoclast (OC) mediated lytic bone disease remains a cause of major morbidity in multiple myeloma (MM). Here we demonstrate the critical role of IL-17 producing marrow infiltrating lymphocytes (MILs) in OC activation and development of bone lesions in myeloma patients. Unlike MILs from normal bone marrow, myeloma MILs possess few regulatory T cells (Tregs) and demonstrate an IL-17 phenotype which enhances OC activation. In univariate analyses of factors mediating bone destruction, levels of cytokines that selectively induce and maintain the Th17 phenotype tightly correlated with the extent of bone disease in myeloma. In contrast, MILs activated under conditions that skew towards a Th1 phenotype significantly reduced formation of mature OC. These findings demonstrate that IL-17 T cells are critical to the genesis of myeloma bone disease, and that immunologic manipulations shifting MILs from a Th17 to a Th1 phenotype may profoundly diminish lytic bone lesions in MM.

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