1. Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2015.169
Figure 4 TNF modulates cellular responses to subsequent challenges and imposes short-term memory
Figure 4 | TNF modulates cellular responses to subsequent challenges and imposes short-term memory. a | TNF-induced cell priming (sensitization). Prolonged exposure to TNF primes the chromatin of fibroblast-like synoviocytes (FLS) in a gene-specific manner, by histone eviction, acetylation of the remaining histones, and loading of nuclear factor κB (NFκB) to specific interferon (IFN)-target genes. In addition, TNF induces the expression of signal transducer and activator of transcription 1 (STAT1), increasing the intracellular STAT1 reservoir. This 'primed' state is maintained for several days, imposing a 'short-term memory' in cells. Primed FLS display hyperresponsiveness to saturating doses and sensitization to suboptimal doses of IFNs. b | TNF-induced cell tolerization (desensitization). TNF induces a 'tolerized' state in macrophages by triggering the expression of A20 via a glycogen synthase kinase 3β (GSK-3β)-dependent mechanism, and by establishing a gene-specific chromatin barrier. A20 attenuates the signalling input and the chromatin barrier prevents gene-expression upon subsequent stimulation with lipopolysaccharide (LPS). TLR, Toll-like receptor.
Kalliolias, G. D. & Ivashkiv, L. B. (2015) TNF biology, pathogenic mechanisms and emerging therapeutic strategies
Nat. Rev. Rheumatol. doi: /nrrheum