Title: A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis
Authors: Matmati, Mourad ×
Jacques, Peggy
Maelfait, Jonathan
Verheugen, Eveline
Kool, Mirjam
Sze, Mozes
Geboes, Lies
Louagie, Els
Guire, Conor Mc
Vereecke, Lars
Chu, Yuanyuan
Boon, Louis
Staelens, Steven
Matthys, Patrick
Lambrecht, Bart N
Schmidt-Supprian, Marc
Pasparakis, Manolis
Elewaut, Dirk
Beyaert, Rudi
van Loo, Geert #
Issue Date: Sep-2011
Publisher: Nature Publishing Group
Series Title: Nature Genetics vol:43 issue:9 pages:908-12
Article number: 10.1038/ng.874
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.
ISSN: 1061-4036
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Immunobiology (Rega Institute)
× corresponding author
# (joint) last author

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