Bone destroying cells (red) flourish in the presence (top) of the IL-17 cytokine.

Autoimmune arthritis, such as rheumatoid arthritis, is a T cell–driven disease, in which bones are destroyed by hyperactive bone-resorbing osteoclasts. Activated T cells have long been implicated in arthritic inflammation and the resulting bone destruction, but exactly which type of T cell is responsible has never been confirmed. T helper (Th)-1 cells, the cells that promote cellular immunity, have received the lion's share of the blame. Yet Th1's signature cytokine, IFN, actually inhibits bone resorption by osteoclasts.

The study by Sato et al. helps resolve this paradox by putting the blame for inflammatory bone destruction on a recently described T cell subset called Th17. Th17 cells, named for their propensity to secrete the cytokine IL-17, have also been implicated in other models of autoimmune inflammation.

The team tested whether various T cell subsets—Th17, Th1, Th2, and regulatory T cells—affected osteoclasts. They found that only Th17 cells enhanced osteoclast differentiation—a prerequisite for bone resorption. IL-17 itself also promoted osteoclast differentiation. The induction of osteoclast differentiation was only seen when bone-forming osteoblast cells were also present in the culture. Osteoblasts provide osteoclasts with differentiation signals; thus it now appears that IL-17 might prompt the osteoblasts to release these signals.

Current treatments for autoimmune arthritis reduce inflammation by using broad-based immunosuppression. The identification of both the specific T cell subset and the cytokine responsible for promoting bone resorption might lead to a more powerful therapy that also targets skeletal damage.