In this study, we fill this gap by showing for the first time that loss of A20 causes spontaneous cerebral inflammation, as demonstrated by robust microglial activation, reactive astrogliosis, endothelial activation, increased oxidative/nitrosative stress and expression of NFκB regulated pro-inflammatory soluble mediators such as IL-1β, TNF, IL-6 and MCP-1 in the brain. The gene discussed is TNF; the disease is inflammatory response.