RAGE Enhances TLR Responses through Binding and Internalization of RNA.

J Immunol 2016 11 19;197(10):4118-4126. Epub 2016 Oct 19.

Institute of Innate Immunity, University Hospital, University of Bonn, 53127 Bonn, Germany;

Nucleic acid recognition is an important mechanism that enables the innate immune system to detect microbial infection and tissue damage. To minimize the recognition of self-derived nucleic acids, all nucleic acid-sensing signaling receptors are sequestered away from the cell surface and are activated in the cytoplasm or in endosomes. Nucleic acid sensing in endosomes relies on members of the TLR family. The receptor for advanced glycation end-products (RAGE) was recently shown to bind DNA at the cell surface, facilitating DNA internalization and subsequent recognition by TLR9. In this article, we show that RAGE binds RNA molecules in a sequence-independent manner and enhances cellular RNA uptake into endosomes. Gain- and loss-of-function studies demonstrate that RAGE increases the sensitivity of all ssRNA-sensing TLRs (TLR7, TLR8, TLR13), suggesting that RAGE is an integral part of the endosomal nucleic acid-sensing system.

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Source
http://dx.doi.org/10.4049/jimmunol.1502169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062438PMC
November 2016
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