A20: a master regulator of arthritis

Table 1 The target and mechanism of A20 regulating arthritis

Target	Pro-inflammation approach	Effect of A20	Consequence
NF-κB	Trigger the formation of numerous pro-inflammatory cytokines like IFN-γ, TNF-α, IL-1β, IL-6	Restrict its activation	Reduced pro-inflammation cytokines
Casp1	Cell pyroptosis	Lower activation of Casp1 and inhibit pyroptosis dependent on Casp1	Cell survival and secretion of cytokines is blocked
Casp1	NLRP3 activation, IL-1 and IL-18 secretion	Downregulate the transcription of NLRP3, ASC, procaspase1, proIL-1, and IL-18	Inhibited NLRP3 assembly and activation
RIPK1	Activation of NF-κB	Remove K63-linked ubiquitin chains from RIPK1 and add K48-linked ubiquitin on RIPK1	Degradation of RIPK1
RIPK1	Substrate of Casp8		Degradation of RIPK1
MAPKs	Secretion of IL-17A	Deubiquitination of TRAF6 and prevent the prolonged phosphorylation of JNK	Blocked IL-17 production
Unphosphorylated RIPK3	Macrophages necroptosis	Reduce phosphorylation of RIPK3	Macrophages survived
TNFR1 signal complexes	Macrophages necroptosis	Protect these complexes from being degraded through ZnF7 domain	Macrophages survived

ISSN: 1478-6362