Nature Medicine 11, 1066 - 1072 (2005)
Published online: 18 September 2005; | doi:10.1038/nm1304
Amelioration of inflammatory arthritis by targeting the pre-ligand assembly domain of tumor necrosis factor receptorsGuo-Min Deng1, Lixin Zheng1, Francis Ka-Ming Chan2
& Michael Lenardo11
Laboratory of Immunology, Building 10, Room 11N311, 10 Center Drive, MSC 1892, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA. 2
Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655-0002, USA.
Correspondence should be addressed to Michael Lenardo lenardo@nih.gov Tumor necrosis factor (TNF)- has an important role in the pathogenesis of autoimmune and inflammatory diseases such as rheumatoid and septic arthritis. The biological effects of TNF- are mediated by binding to TNF receptors TNFR1 (also known as P60) or TNFR2 (also known as P80). The pre-ligand assembly domain (PLAD) is a portion of the extracellular region of TNFRs that mediates receptor-chain association essential for signaling. We found that soluble versions of PLAD, especially those derived from P60, block the biochemical effects of TNF- in vitro and potently inhibit arthritis in animal models. Thus, targeting the PLAD may have clinical value in the treatment of human arthritis and other disorders involving receptors of the TNFR superfamily.
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