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

Mourad Matmati (UGent) , Peggy Jacques (UGent) , Jonathan Maelfait (UGent) , Eveline Verheugen (UGent) , Mirjam Kool (UGent) , Mozes Sze (UGent) , Lies Geboes, Els Louagie (UGent) , Conor Mc Guire (UGent) , Lars Vereecke (UGent) , et al.
(2011) NATURE GENETICS. 43(9). p.908-U129
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Abstract
A20 (TNFAIP3) is a protein that is involved in the negative feedback regulation of NF-kappa B 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-kappa B 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.
Keywords
OSTEOCLASTOGENESIS, INFLAMMATION, ANTIBODIES, INFECTION, MICE LACKING, RECEPTOR, ENZYME A20, ESCHERICHIA-COLI, NF-KAPPA-B, PATHOGENESIS

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MLA
Matmati, Mourad, Peggy Jacques, Jonathan Maelfait, et al. “A20 (TNFAIP3) Deficiency in Myeloid Cells Triggers Erosive Polyarthritis Resembling Rheumatoid Arthritis.” NATURE GENETICS 43.9 (2011): 908–U129. Print.
APA
Matmati, M., Jacques, P., Maelfait, J., Verheugen, E., Kool, M., Sze, M., Geboes, L., et al. (2011). A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis. NATURE GENETICS, 43(9), 908–U129.
Chicago author-date
Matmati, Mourad, Peggy Jacques, Jonathan Maelfait, Eveline Verheugen, Mirjam Kool, Mozes Sze, Lies Geboes, et al. 2011. “A20 (TNFAIP3) Deficiency in Myeloid Cells Triggers Erosive Polyarthritis Resembling Rheumatoid Arthritis.” Nature Genetics 43 (9): 908–U129.
Chicago author-date (all authors)
Matmati, Mourad, 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 Lambrecht, Marc Schmidt-Supprian, Manolis Pasparakis, Dirk Elewaut, Rudi Beyaert, and Geert van Loo. 2011. “A20 (TNFAIP3) Deficiency in Myeloid Cells Triggers Erosive Polyarthritis Resembling Rheumatoid Arthritis.” Nature Genetics 43 (9): 908–U129.
Vancouver
1.
Matmati M, Jacques P, Maelfait J, Verheugen E, Kool M, Sze M, et al. A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis. NATURE GENETICS. 2011;43(9):908–U129.
IEEE
[1]
M. Matmati et al., “A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis,” NATURE GENETICS, vol. 43, no. 9, pp. 908-U129, 2011.
@article{1917648,
  abstract     = {A20 (TNFAIP3) is a protein that is involved in the negative feedback regulation of NF-kappa B 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-kappa B 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.},
  author       = {Matmati, Mourad and Jacques, Peggy and Maelfait, Jonathan and Verheugen, Eveline and Kool, Mirjam and Sze, Mozes and Geboes, Lies and Louagie, Els and Mc Guire, Conor and Vereecke, Lars and Chu, Yuanyuan and Boon, Louis and Staelens, Steven and Matthys, Patrick and Lambrecht, Bart and Schmidt-Supprian, Marc and Pasparakis, Manolis and Elewaut, Dirk and Beyaert, Rudi and van Loo, Geert},
  issn         = {1061-4036},
  journal      = {NATURE GENETICS},
  keywords     = {OSTEOCLASTOGENESIS,INFLAMMATION,ANTIBODIES,INFECTION,MICE LACKING,RECEPTOR,ENZYME A20,ESCHERICHIA-COLI,NF-KAPPA-B,PATHOGENESIS},
  language     = {eng},
  number       = {9},
  pages        = {908--U129},
  title        = {A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis},
  url          = {http://dx.doi.org/10.1038/ng.874},
  volume       = {43},
  year         = {2011},
}

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