| First Author | Matmati M | Year | 2011 |
| Journal | Nat Genet | Volume | 43 |
| Issue | 9 | Pages | 908-12 |
| PubMed ID | 21841782 | Mgi Jnum | J:176518 |
| Mgi Id | MGI:5292158 | Doi | 10.1038/ng.874 |
| Citation | Matmati M, et al. (2011) A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis. Nat Genet 43(9):908-12 |
| abstractText | A20 (TNFAIP3) is a protein that is involved in the negative feedback regulation of NF-kappaB 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-kappaB 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. |
