Figure 4.

Proposed consequences of ERE immunogenicity, depending on the degree of ERE activity. In physiological conditions (a), ERE transcriptional activity is epigenetically controlled and their products eliminated in most cells, with the exception of infected, transformed, senescent, or otherwise stressed cells. In turn, this prevents interferon responses and priming of adaptive immune cells against the low level of ERE products in healthy cells but permits immune reactions against elevated ERE products in stressed cells. Such regulated responses are thought to contribute to several physiological processes. In contrast, when ERE transcription is unleashed (b), through loss of epigenetic control, or their products accumulate, through loss of nucleic acid metabolism or editing machineries, in a sufficient number of otherwise healthy cells, the resulting excessive interferon and adaptive immune responses can trigger or contribute to a range of pathological conditions. Abbreviation: ERE, endogenous retroelement.