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SP0021 Complement C5A and immune-complexes promote TNF-dependent pathologies via stimulation of the TNF-alpha convertase (TACE)
  1. C. Blobel
  1. Arthritis and Tissue Degeneration, Hospital for Special Surgery, New York, United States

Abstract

Rheumatoid arthritis (RA) is triggered by inflammatory mediators such as anaphylatoxin C5a and immune-complexes, yet much remains to be learned about the underlying mechanisms. Here, we show that C5a and immune-complexes activate the principal TNFα convertase, TACE, thereby triggering release of TNFα. TACE belongs to the ADAM (a disintegrin and metalloproteinase) family of membrane-anchored metalloproteinases, which have emerged as key regulators of cell-cell interactions. Mice lacking TACE in myeloid cells are protected from inflammatory arthritis in the K/BxN serum transfer model of RA, providing the first genetic evidence for a critical role for TACE in myeloid cells in the pathogenesis of RA. These results support the notion that TACE is an attractive target for treatment of TNFα-dependent pathologies.

Disclosure of Interest None Declared

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