Proposed model of the role of IL-17–producing MILs in myeloma bone disease. The tumor microenvironment, consisting of plasma cells, stromal elements, and MILs, produces IL-6, TGF-β, IL-1β, and IL-23. The excess of IL-6 compared with TGF-β causes a shift from a Treg (predominantly found in a normal BM) to a Th17 cell, which in turn increases T-cell production of IL-17 and RANKL. These 2 cytokines together with MIP-1α subsequently act on OC precursors (Op) to increase osteoclastogenesis. The addition of IFN-γ–producing T cells inhibits osteoclastogenesis.