NKT cells aggravate arthritis by blocking TGF-β.
NKT cells are innate immune cells that express both NK and T cell markers, and are protective in many other models of autoimmune disease. The authors tested NKT function in K/BxN mice—an established model of rheumatoid arthritis. These mice spontaneously develop a progressive inflammatory disease that is caused by the deposition of autoantibodies in joints. Disease can be transferred to healthy recipient mice by injecting them with K/BxN serum.Kim et al. now show that mice lacking NKT cells develop only mild joint inflammation when given K/BxN serum. This protection was reversed if the deficient mice were reconstituted with NKT cells.
The nonarthritic mice lacking NKT cells had high levels of TGF-β1 in their joints, which dropped as soon as the NKT cells arrived on the scene. Blocking TGF-β1 in the same NKT cell–deficient mice increased joint swelling, suggesting a protective role for this cytokine. Suppression of TGF-β1 production depended on the ability of the NKT cells to produce both IL-4 and IFN-γ.
Many questions remain unanswered. Future studies might reveal which cells produce the TGF-β1 in the joints, how TGF-β1 prevents arthritis, what attracts NKT cells to the joint, and how NKT cells suppress TGF-β1 production.
