LINE1 contributes to autoimmunity through both RIG-I- and MDA5-mediated RNA sensing pathways.

In this study, we report that endogenous LINE1 components trigger IFNβ production in multiple human cell types, including those defective for cGAS/STING-mediated DNA sensing. In these cells, LINE1 DNA synthesis and retrotransposition were not required for LINE1-triggered immune activation, but RNA sensing pathways were essential. LINE1-triggered immune activation could be suppressed by diverse LINE1 inhibitors, including AGS-associated proteins targeting LINE1 RNA or proteins. However, AGS-associated ADAR1 or TREX1 mutants were defective in suppressing LINE1 retrotransposition or LINE1-triggered immune activation. Therefore, we have revealed a new function for LINE1 as an endogenous trigger of innate immune activation, which is important for understanding the molecular basis of IFN-based autoimmune diseases and may offer new intervention strategies. PMID: 29525183 [PubMed - as supplied by publisher]
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research