Rheumatoid arthritis is a systemic autoimmune disease that principally affects synovial joints, including knee, finger, hip, and wrist. The inflammatory cytokine tumor necrosis factor–α (TNFα) contributes to disease pathogenesis, and targeted therapies against TNFα are currently in use. Because the therapeutic efficacy and side effects of anti-TNFα treatments differ among patients, there is interest in discovering new therapies. Tang et al. (see the Perspective by Wu and Siegel) now report that the growth factor progranulin may represent a potential therapeutic target in the treatment of rheumatoid arthritis. Progranulin binds directly to TNF receptors 1 and 2 and competes with TNFα for receptor binding. Progranulin deficiency protected against the development of inflammatory arthritis in multiple mouse models of the disease. Furthermore, an engineered protein composed of peptide fragments of progranulin retained TNF receptor binding, prevented the development of inflammatory arthritis in mouse models, and decreased the mouse disease symptoms when used therapeutically.
W. Tang, Y. Lu, Q.-Y. Tian, Y. Zhang, F.-J. Guo, G.-Y. Liu, N. M. Syed, Y. Lai, E. A. Lin, L. Kong, J. Su, F. Yin, A.-H. Ding, A. Zanin-Zhorov, M. L. Dustin, J. Tao, J. Craft, Z. Yin, J. Q. Feng, S. B. Abramson, X.-P. Yu, C.-j. Liu, The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 332, 478–484 (2011). [Abstract] [Full Text]