Inhibition of specific signaling pathways rather than epigenetic silencing of effector genes is the leading mechanism of innate toleranceстатьяЭлектронная публикация
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus
Аннотация:Macrophages activated through a pattern-recognition receptor (PRR) enter a transient state of tolerance characterized by diminished responsiveness to restimulation of the same receptor. Signaling-based and epigenetic mechanisms are invoked to explain this innate tolerance. However, these two groups of mechanisms should result in different outcomes. The epigenetic scenario (silencing of effector genes) predicts that activation of a PRR should broadly cross-tolerize to agonists of unrelated PRRs, whereas in the signaling-based scenario (inhibition of signaling pathways downstream of specific PRRs), cross-tolerization should occur only between agonists utilizing the same PRR and/or signaling pathway. Also, the so-called non-tolerizeable genes have been described, which acquire distinct epigenetic marks and increased responsiveness to rechallenge with the same agonist. The existence of such genes is well explained by epigenetic mechanisms but difficult to explain solely by signaling mechanisms.