Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers
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 trigger...
| Main Authors: | , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2017
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| Online Access: | https://eprints.nottingham.ac.uk/48271/ |
| _version_ | 1848797728950190080 |
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| author | Zuliani-Alvarez, Lorena Marzeda, Anna M. Deligne, Claire Schwenzer, Anja McCann, Fiona E. Marsden, Brian D. Piccinini, Anna M. Midwood, Kim S. |
| author_facet | Zuliani-Alvarez, Lorena Marzeda, Anna M. Deligne, Claire Schwenzer, Anja McCann, Fiona E. Marsden, Brian D. Piccinini, Anna M. Midwood, Kim S. |
| author_sort | Zuliani-Alvarez, Lorena |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:08:30Z |
| format | Article |
| id | nottingham-48271 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:08:30Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-482712020-05-04T19:18:51Z https://eprints.nottingham.ac.uk/48271/ Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers Zuliani-Alvarez, Lorena Marzeda, Anna M. Deligne, Claire Schwenzer, Anja McCann, Fiona E. Marsden, Brian D. Piccinini, Anna M. Midwood, Kim S. 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. Nature Publishing Group 2017-11-17 Article PeerReviewed Zuliani-Alvarez, Lorena, Marzeda, Anna M., Deligne, Claire, Schwenzer, Anja, McCann, Fiona E., Marsden, Brian D., 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 https://www.nature.com/articles/s41467-017-01718-7 doi:10.1038/s41467-017-01718-7 doi:10.1038/s41467-017-01718-7 |
| spellingShingle | Zuliani-Alvarez, Lorena Marzeda, Anna M. Deligne, Claire Schwenzer, Anja McCann, Fiona E. Marsden, Brian D. Piccinini, Anna M. Midwood, Kim S. Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers |
| title | Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers |
| title_full | Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers |
| title_fullStr | Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers |
| title_full_unstemmed | Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers |
| title_short | Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers |
| title_sort | mapping tenascin-c interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers |
| url | https://eprints.nottingham.ac.uk/48271/ https://eprints.nottingham.ac.uk/48271/ https://eprints.nottingham.ac.uk/48271/ |