T Cell Role for Cathepsin K

Cathepsins are cysteine proteases that degrade proteins in the lysosome, and some cathepsins assist with the processing of antigens for the immune system. Asagiri et al. (see the Perspective by Krieg and Lipford) uncover a further but distinct immunological role for another cathepsin, cathepsin K, which is known to be involved in osteoclast function in the bone. Cathepsin K is expressed in immunological dendritic cells and is needed for the complete induction of the inflammatory T helper 17 cells. In animal models for two autoimmune conditions, pathology was ameliorated by cathepsin K deficiency because of its unexpected involvement in signaling through the innate immune receptor TLR9. Cathepsin K is already a target for some antirheumatic drugs, so its emergence as regulator of the immune response may further bolster efforts to target this pathway. M. Asagiri, T. Hirai, T. Kunigami, S. Kamano, H.-J. Gober, K. Okamoto, K. Nishikawa, E. Latz, D. T. Golenbock, K. Aoki, K. Ohya, Y. Imai, Y. Morishita, K. Miyazono, S. Kato, P. Saftig, H. Takayanagi, Cathepsin K-dependent Toll-like receptor 9 signaling revealed in experimental arthritis. Science 319 , 624-627 (2008). [Abstract][Full Text] A. M. Krieg, G. B. Lipford, The Toll of cathepsin K deficiency. Science 319 , 576-577 (2008). [Summary][Full Text]