A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis (Nat Genetics, 2011, 43:908-912)

報告日期: 2012/10/23
報告時間: 17:10/18:00
報告學生: 周妤
講評老師: 張明熙
附件下載: 下載[1224-1348566756-1.pdf] 

A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis

Mourad Matmati, Peggy Jacques, Jonathan Maelfait., et al. 2011. Nat Genet. 43, 908-12

Speaker: Zhou Yu (周妤)     Commentator: Dr. Ming-Shi Chang (張明熙博士)

Time: 17:10~18:00, Oct. 23, 2012     Place: Room 602

Abstract:

Rheumatoid arthritis (RA) is a common autoimmune inflammatory disease characterised by chronic inflammation and destruction of synovial joints leading to progressive disability. The activation of nuclear factor-κB (NF-κB)-dependent gene expression is one of accepted etiologies in the development of rheumatoid arthritis. The intracellular deubiquitinating protein A20 (also known as tumor necrosis factor alpha-induced protein 3, TNFAIP3) is a negative regulator of NF-κB signaling pathway in response to different immune-activating stimuli. To confirm the role of A20 in RA, the authors generated myeloid-specific A20-deficient (A20myel-KO) mice and found the mice had spontaneous development of severe destructive polyarthritis with many features of rheumatoid arthritis. The A20myel-KOmice had high serum titers of inflammatory and rheumatoid arthritis–associated cytokines. The authors discovered that the development of destructive polyarthritis in A20myel-KO was dependent on the activation of signaling pathways of TLR4-MyD88 and IL-6 but not TNF. In addition, the A20myel-KO mice also had splenomegaly and enlargement of inguinal and axillary lymph nodes and their blood leukocytes were prone to osteoclastogenesis. In summary, this study provides an evidence supporting that A20 could play a critical role of rheumatoid arthritis and to be a good therapeutic target.

References:

1.         Vereecke L, Beyaert R, van Loo G. 2009. The ubiquitin-editing enzyme A20 (TNFAIP3)is a central regulator of immunopathology. Trends Immunol. 30, 383-91.

2.         Rothe J, Lesslauer W, Lötscher H., et al. 1993. Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature.364, 798-802.