Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers

Zuliani-Alvarez, Lorena and Marzeda, Anna M. and Deligne, Claire and Schwenzer, Anja and McCann, Fiona E. and Marsden, Brian D. and Piccinini, Anna M. and Midwood, Kim S. (2017) Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers. Nature Communications, 8 (1). ISSN 2041-1723

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Abstract

Pattern recognition underpins innate immunity; the accurate identification of danger, including infection, injury, or tumor, is key to an appropriately targeted immune response. Pathogen detection is increasingly well defined mechanistically, but the discrimination of endogenous inflammatory triggers remains unclear. Tenascin-C, a matrix protein induced upon tissue damage and expressed by tumors, activates toll-like receptor 4 (TLR4)-mediated sterile inflammation. Here we map three sites within tenascin-C that directly and cooperatively interact with TLR4. We also identify a conserved inflammatory epitope in related proteins from diverse families, and demonstrate that its presence targets molecules for TLR detection, while its absence enables escape of innate immune surveillance. These data reveal a unique molecular code that defines endogenous proteins as inflammatory stimuli by marking them for recognition by TLRs.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Pharmacy
Identification Number: 10.1038/s41467-017-01718-7
Depositing User: Eprints, Support
Date Deposited: 20 Nov 2017 14:40
Last Modified: 14 Dec 2017 10:36
URI: http://eprints.nottingham.ac.uk/id/eprint/48271

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