Schematic diagram summarizing the role of IL-17–producing lymphocytes in bone disease in myeloma. The bone and the bone marrow are immunologically active sites. (1) Myeloma cell–stromal interaction leads to up-regulation of factors such as IL-6, TGF-β, IL-1β, IL-23, and RANKL The first 2 factors in particular will induce IL-17–producing lymphocytes which also express RANKL. (2) Both factors in turn will act upon osteoclast precursors (Op) and increase osteoclast generation and/or activity. (3) IL-17 also increases adherence of myeloma cells expressing IL17R to BM stromal elements by functioning as a myeloma growth factor. (4) Dendritic cells might also contribute to the induction of Th17 cells in the BM of myeloma patients.