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

References

1. Coornaert, B., Carpentier, I. & Beyaert, R. A20: central gatekeeper in inflammation and immunity. J. Biol. Chem. 284, 8217–8221 (2009).
   Article CAS Google Scholar
2. Wertz, I.E. et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling. Nature 430, 694–699 (2004).
   Article CAS Google Scholar
3. Boone, D.L. et al. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat. Immunol. 5, 1052–1060 (2004).
   Article CAS Google Scholar
4. Hitotsumatsu, O. et al. The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signals. Immunity 28, 381–390 (2008).
   Article CAS Google Scholar
5. Düwel, M. et al. A20 negatively regulates T cell receptor signaling to NF-κB by cleaving Malt1 ubiquitin chains. J. Immunol. 182, 7718–7728 (2009).
   Article Google Scholar
6. Lee, E.G. et al. Failure to regulate TNF-induced NF-κB and cell death responses in A20-deficient mice. Science 289, 2350–2354 (2000).
   Article CAS Google Scholar
7. Vereecke, L., Beyaert, R. & van Loo, G. The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. Trends Immunol. 30, 383–391 (2009).
   Article CAS Google Scholar
8. Vereecke, L. et al. Enterocyte-specific A20 deficiency sensitizes to tumor necrosis factor-induced toxicity and experimental colitis. J. Exp. Med. 207, 1513–1523 (2010).
   Article CAS Google Scholar
9. Clausen, B.E., Burkhardt, C., Reith, W., Renkawitz, R. & Forster, I. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res. 8, 265–277 (1999).
   Article CAS Google Scholar
10. Turer, E.E. et al. Homeostatic MyD88-dependent signals cause lethal inflamMation in the absence of A20. J. Exp. Med. 205, 451–464 (2008).
    Article CAS Google Scholar
11. Taylor, P.C. & Feldmann, M. Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis. Nat. Rev. Rheumatol. 5, 578–582 (2009).
    Article CAS Google Scholar
12. Rothe, J. et al. 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 (1993).
    Article CAS Google Scholar
13. Huang, Q.Q. & Pope, R.M. The role of Toll-like receptors in rheumatoid arthritis. Curr. Rheumatol. Rep. 11, 357–364 (2009).
    Article CAS Google Scholar
14. Hennessy, E.J., Parker, A.E. & O'Neill, L.A. Targeting Toll-like receptors: emerging therapeutics? Nat. Rev. Drug Discov. 9, 293–307 (2010).
    Article CAS Google Scholar
15. Adachi, O. et al. Targeted disruption of the MyD88 gene results in loss of IL-1– and IL-18–mediated function. Immunity 9, 143–150 (1998).
    Article CAS Google Scholar
16. Aoki, S. et al. Role of enteric bacteria in the pathogenesis of rheumatoid arthritis: evidence for antibodies to enterobacterial common antigens in rheumatoid sera and synovial fluids. Ann. Rheum. Dis. 55, 363–369 (1996).
    Article CAS Google Scholar
17. Yoshino, S., Sasatomi, E., Mori, Y. & Sagai, M. Oral administration of lipopolysaccharide exacerbates collagen-induced arthritis in mice. J. Immunol. 163, 3417–3422 (1999).
    CAS PubMed Google Scholar
18. Nieuwenhuis, E.E. et al. Oral antibiotics as a novel therapy for arthritis: evidence for a beneficial effect of intestinal Escherichia coli. Arthritis Rheum. 43, 2583–2589 (2000).
    Article CAS Google Scholar
19. Vaahtovuo, J., Munukka, E., Korkeamaki, M., Luukkainen, R. & Toivanen, P. Fecal microbiota in early rheumatoid arthritis. J. Rheumatol. 35, 1500–1505 (2008).
    CAS PubMed Google Scholar
20. McInnes, I.B. & Schett, G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat. Rev. Immunol. 7, 429–442 (2007).
    Article CAS Google Scholar
21. Sato, K. et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J. Exp. Med. 203, 2673–2682 (2006).
    Article CAS Google Scholar
22. Shinkai, Y. et al. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68, 855–867 (1992).
    Article CAS Google Scholar
23. Wada, T., Nakashima, T., Hiroshi, N. & Penninger, J.M. RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol. Med. 12, 17–25 (2006).
    Article CAS Google Scholar
24. Li, J. et al. RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc. Natl. Acad. Sci. USA 97, 1566–1571 (2000).
    Article CAS Google Scholar
25. Criscione, L.G. & St. Clair, E.W. Tumor necrosis factor-α antagonists for the treatment of rheumatic diseases. Curr. Opin. Rheumatol. 14, 204–211 (2002).
    Article CAS Google Scholar
26. Plenge, R.M. et al. Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat. Genet. 39, 1477–1482 (2007).
    Article CAS Google Scholar
27. Thomson, W. et al. Rheumatoid arthritis association at 6q23. Nat. Genet. 39, 1431–1433 (2007).
    Article CAS Google Scholar
28. Rodríguez, C.I. et al. High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat. Genet. 25, 139–140 (2000).
    Article Google Scholar
29. Onizawa, M. et al. Signaling pathway via TNF-α/NF-κB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G850–G859 (2009).
    Article CAS Google Scholar
30. Starnes, H.F. et al. Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumor necrosis factor-α challenge in mice. J. Immunol. 145, 4185–4191 (1990).
    CAS PubMed Google Scholar
31. Geboes, L. et al. Freund's complete adjuvant induces arthritis in mice lacking a functional interferon-γ receptor by triggering tumor necrosis factor α-driven osteoclastogenesis. Arthritis Rheum. 56, 2595–2607 (2007).
    Article CAS Google Scholar

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Acknowledgements

We are grateful to I. Förster for donating the LysM-Cre transgenic mice. We thank H. Heremans for providing us with the IL-6 and control antibodies. We thank T. Hochepied for transgenic services, P. Bogaert and E. Parthoens for technical help, A. Bredan for critical reading of the manuscript and D. Huyghebaert and L. Bellen for animal care. L.V. and J.M. are PhD fellows with the Instituut voor Innovatie door Wetenschap en Technologie (IWT), and J.M. is also supported by an Emmanuel van der Schueren award. C.M.G., L.G. and P.J. are PhD fellows with the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO). G.v.L. is supported, as a postdoctoral researcher, by the FWO, by an FWO Odysseus Grant and by the Charcot Foundation. M.K. is supported by an Intra European fellowship from the Marie Curie Actions. M.P. is supported by an FP7 EC program grant Masterswitch (EC-223404). B.N.L. is supported by an FWO Odysseus grant, a European Research Council Starting grant and the Group-ID Multidisciplinary Research Partnership grant of Ghent University. Work in the lab of R.B. and G.v.L. is further supported by research grants from the Interuniversity Attraction Poles program (IAP6/18), the FWO, the Belgian Foundation against Cancer, the Strategic Basis Research program of the IWT, the Centrum voor Gezwelziekten, the Hercules Foundation, and the Concerted Research Actions (GOA) and Group-ID MRP of Ghent University.

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Author notes

1. Mourad Matmati and Peggy Jacques: These authors contributed equally to this work.
2. Dirk Elewaut, Rudi Beyaert and Geert van Loo: These authors jointly directed this work.
3. dirk.elewaut@ugent.be

Authors and Affiliations

1. Department for Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, Vlaams Instituut voor Biotechnologie (VIB), Ghent, Belgium
   Mourad Matmati, Jonathan Maelfait, Mirjam Kool, Mozes Sze, Conor Mc Guire, Lars Vereecke, Rudi Beyaert & Geert van Loo
2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
   Mourad Matmati, Jonathan Maelfait, Mozes Sze, Conor Mc Guire, Lars Vereecke, Rudi Beyaert & Geert van Loo
3. Department of Rheumatology, Laboratory for Molecular Immunology and Inflammation, Ghent University Hospital, Ghent, Belgium
   Peggy Jacques, Eveline Verheugen, Els Louagie & Dirk Elewaut
4. Department of Respiratory Diseases, Laboratory of Immunoregulation and Mucosal Immunology, Ghent University Hospital, Ghent, Belgium
   Mirjam Kool & Bart N Lambrecht
5. Rega Institute, Leuven University, Leuven, Belgium
   Lies Geboes & Patrick Matthys
6. Max Planck Institute of Biochemistry, Martinsried, Germany
   Yuanyuan Chu & Marc Schmidt-Supprian
7. Bioceros, Utrecht, The Netherlands
   Louis Boon
8. Medical Image and Signal Processing, Ghent University and Institute for Broadband Technology, Ghent, Belgium
   Steven Staelens
9. Molecular Imaging Center Antwerp, Antwerp University, Antwerp, Belgium
   Steven Staelens
10. Institute for Genetics, Centre for Molecular Medicine (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
    Manolis Pasparakis

Authors

1. Mourad Matmati
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2. Peggy Jacques
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3. Jonathan Maelfait
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4. Eveline Verheugen
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5. Mirjam Kool
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6. Mozes Sze
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7. Lies Geboes
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8. Els Louagie
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9. Conor Mc Guire
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10. Lars Vereecke
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11. Yuanyuan Chu
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12. Louis Boon
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13. Steven Staelens
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14. Patrick Matthys
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15. Bart N Lambrecht
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16. Marc Schmidt-Supprian
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17. Manolis Pasparakis
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18. Dirk Elewaut
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19. Rudi Beyaert
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20. Geert van Loo
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Contributions

M.M., P.J., J.M., E.V., M.K., M.S., L.G., E.L., C.M.G., L.V., S.S. and G.v.L. performed the experiments. M.M., P.J., C.M.G., S.S., P.M., B.N.L., M.P., D.E., R.B. and G.v.L. analyzed the data. Y.C., L.B., P.M., M.S.-S. and M.P. provided materials. D.E., R.B. and G.v.L. provided ideas and coordinated the project. R.B. and G.v.L. wrote the manuscript.

Corresponding authors

Correspondence toRudi Beyaert or Geert van Loo.

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The authors declare no competing financial interests.

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Matmati, M., Jacques, P., Maelfait, J. et al. A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis.Nat Genet 43, 908–912 (2011). https://doi.org/10.1038/ng.874

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• Received: 22 April 2011
• Accepted: 29 July 2011
• Published: 14 August 2011
• Issue Date: September 2011
• DOI: https://doi.org/10.1038/ng.874