Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Aug 14;43(9):908-12.
doi: 10.1038/ng.874.

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

Mourad Matmati  1 , Peggy Jacques, Jonathan Maelfait, Eveline Verheugen, Mirjam Kool, Mozes Sze, Lies Geboes, Els Louagie, Conor Mc Guire, Lars Vereecke, Yuanyuan Chu, Louis Boon, Steven Staelens, Patrick Matthys, Bart N Lambrecht, Marc Schmidt-Supprian, Manolis Pasparakis, Dirk Elewaut, Rudi Beyaert, Geert van Loo
Affiliations

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

Mourad Matmati et al. Nat Genet. .

Abstract

A20 (TNFAIP3) is a protein that is involved in the negative feedback regulation of NF-κB signaling in response to specific proinflammatory stimuli in different cell types and has been suggested as a susceptibility gene for rheumatoid arthritis. To define the contribution of A20 to rheumatoid arthritis pathology, we generated myeloid-specific A20-deficient mice and show that specific ablation of Tnfaip3 in myeloid cells results in spontaneous development of a severe destructive polyarthritis with many features of rheumatoid arthritis. Myeloid-A20-deficient mice have high levels of inflammatory cytokines in their serum, consistent with a sustained NF-κB activation and higher TNF production by macrophages. Destructive polyarthritis in myeloid A20 knockout mice was TLR4-MyD88 and IL-6 dependent but was TNF independent. Myeloid A20 deficiency also promoted osteoclastogenesis in mice. Together, these observations indicate a critical and cell-specific function for A20 in the etiology of rheumatoid arthritis, supporting the idea of developing A20 modulatory drugs as cell-targeted therapies.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Nat Genet. 2007 Dec;39(12):1431-3 - PubMed
    1. Curr Opin Rheumatol. 2002 May;14(3):204-11 - PubMed
    1. Trends Mol Med. 2006 Jan;12(1):17-25 - PubMed
    1. Nature. 2004 Aug 5;430(7000):694-9 - PubMed
    1. J Rheumatol. 2008 Aug;35(8):1500-5 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources