Type I interferon (IFN) production by the proper activation of nucleic acid sensors is essential for hosts to eliminate invading viruses. Among these sensors, RIG-I-like receptors (RLRs) are well-known viral RNA sensors in the cytoplasm that recognize the nonself signatures of viral RNAs to trigger IFN responses. Recent accumulating evidence has clarified that some specific and atypical self-RNAs also cause activation of RLRs independently of virus infection. Importantly, when RLR-activation by these RNAs or a conformational change via missense mutations is sustained, the resulting continuous production of type I IFN will lead to autoimmune disorders. We, herein, focus on autoimmune diseases caused by chronic activation of RLRs and discuss possible mechanisms of their onset.
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