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A20 prevents inflammasome-dependent arthritis by inhibiting macrophage necroptosis through its ZnF7 ubiquitin-binding domain

(2019) NATURE CELL BIOLOGY. 21(6). p.731-742
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Abstract
Deficiency in the deubiquitinating enzyme A20 causes severe inflammation in mice, and impaired A20 function is associated with human inflammatory diseases. A20 has been implicated in negatively regulating NF-.B signalling, cell death and inflammasome activation; however, the mechanisms by which A20 inhibits inflammation in vivo remain poorly understood. Genetic studies in mice revealed that its deubiquitinase activity is not essential for A20 anti-inflammatory function. Here we show that A20 prevents inflammasome-dependent arthritis by inhibiting macrophage necroptosis and that this function depends on its zinc finger 7 (ZnF7). We provide genetic evidence that RIPK1 kinase-dependent, RIPK3-MLKL-mediated necroptosis drives inflammasome activation in A20-deficient macrophages and causes inflammatory arthritis in mice. Single-cell imaging revealed that RIPK3-dependent death caused inflammasome-dependent IL-1 beta release from lipopolysaccharide-stimulated A20-deficient macrophages. Importantly, mutation of the A20 ZnF7 ubiquitin binding domain caused arthritis in mice, arguing that ZnF7-dependent inhibition of necroptosis is critical for A20 anti-inflammatory function in vivo.
Keywords
NF-KAPPA-B, NLRP3 INFLAMMASOME, CELL-DEATH, RESTRICTS UBIQUITINATION, LINEAR POLYUBIQUITIN, TNFAIP3 A20, TNF, ACTIVATION, GENE, DEFICIENCY

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MLA
Polykratis, Apostolos et al. “A20 Prevents Inflammasome-dependent Arthritis by Inhibiting Macrophage Necroptosis Through Its ZnF7 Ubiquitin-binding Domain.” NATURE CELL BIOLOGY 21.6 (2019): 731–742. Print.
APA
Polykratis, A., Martens, A., Eren, R. O., Shirasaki, Y., Yamagishi, M., Yamaguchi, Y., Uemura, S., et al. (2019). A20 prevents inflammasome-dependent arthritis by inhibiting macrophage necroptosis through its ZnF7 ubiquitin-binding domain. NATURE CELL BIOLOGY, 21(6), 731–742.
Chicago author-date
Polykratis, Apostolos, Arne Martens, Remzi Onur Eren, Yoshitaka Shirasaki, Mai Yamagishi, Yoshifumi Yamaguchi, Sotaro Uemura, et al. 2019. “A20 Prevents Inflammasome-dependent Arthritis by Inhibiting Macrophage Necroptosis Through Its ZnF7 Ubiquitin-binding Domain.” Nature Cell Biology 21 (6): 731–742.
Chicago author-date (all authors)
Polykratis, Apostolos, Arne Martens, Remzi Onur Eren, Yoshitaka Shirasaki, Mai Yamagishi, Yoshifumi Yamaguchi, Sotaro Uemura, Masayuki Miura, Bernhard Holzmann, George Kollias, Marietta Armaka, Geert van Loo, and Manolis Pasparakis. 2019. “A20 Prevents Inflammasome-dependent Arthritis by Inhibiting Macrophage Necroptosis Through Its ZnF7 Ubiquitin-binding Domain.” Nature Cell Biology 21 (6): 731–742.
Vancouver
1.
Polykratis A, Martens A, Eren RO, Shirasaki Y, Yamagishi M, Yamaguchi Y, et al. A20 prevents inflammasome-dependent arthritis by inhibiting macrophage necroptosis through its ZnF7 ubiquitin-binding domain. NATURE CELL BIOLOGY. 2019;21(6):731–42.
IEEE
[1]
A. Polykratis et al., “A20 prevents inflammasome-dependent arthritis by inhibiting macrophage necroptosis through its ZnF7 ubiquitin-binding domain,” NATURE CELL BIOLOGY, vol. 21, no. 6, pp. 731–742, 2019.
@article{8622857,
  abstract     = {Deficiency in the deubiquitinating enzyme A20 causes severe inflammation in mice, and impaired A20 function is associated with human inflammatory diseases. A20 has been implicated in negatively regulating NF-.B signalling, cell death and inflammasome activation; however, the mechanisms by which A20 inhibits inflammation in vivo remain poorly understood. Genetic studies in mice revealed that its deubiquitinase activity is not essential for A20 anti-inflammatory function. Here we show that A20 prevents inflammasome-dependent arthritis by inhibiting macrophage necroptosis and that this function depends on its zinc finger 7 (ZnF7). We provide genetic evidence that RIPK1 kinase-dependent, RIPK3-MLKL-mediated necroptosis drives inflammasome activation in A20-deficient macrophages and causes inflammatory arthritis in mice. Single-cell imaging revealed that RIPK3-dependent death caused inflammasome-dependent IL-1 beta release from lipopolysaccharide-stimulated A20-deficient macrophages. Importantly, mutation of the A20 ZnF7 ubiquitin binding domain caused arthritis in mice, arguing that ZnF7-dependent inhibition of necroptosis is critical for A20 anti-inflammatory function in vivo.},
  author       = {Polykratis, Apostolos and Martens, Arne and Eren, Remzi Onur and Shirasaki, Yoshitaka and Yamagishi, Mai and Yamaguchi, Yoshifumi and Uemura, Sotaro and Miura, Masayuki and Holzmann, Bernhard and Kollias, George and Armaka, Marietta and van Loo, Geert and Pasparakis, Manolis},
  issn         = {1465-7392},
  journal      = {NATURE CELL BIOLOGY},
  keywords     = {NF-KAPPA-B,NLRP3 INFLAMMASOME,CELL-DEATH,RESTRICTS UBIQUITINATION,LINEAR POLYUBIQUITIN,TNFAIP3 A20,TNF,ACTIVATION,GENE,DEFICIENCY},
  language     = {eng},
  number       = {6},
  pages        = {731--742},
  title        = {A20 prevents inflammasome-dependent arthritis by inhibiting macrophage necroptosis through its ZnF7 ubiquitin-binding domain},
  url          = {http://dx.doi.org/10.1038/s41556-019-0324-3},
  volume       = {21},
  year         = {2019},
}

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