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Nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes
BACKGROUND: NOD-like receptors (Nlrs) are key regulators of immune responses during infection and autoimmunity. A subset of Nlrs assembles inflammasomes, molecular platforms that are activated in response to endogenous danger and microbial ligands and that control release of interleukin (IL)-1β and...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528710/ https://www.ncbi.nlm.nih.gov/pubmed/26253422 http://dx.doi.org/10.1186/s12974-015-0367-8 |
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author | Ydens, Elke Demon, Dieter Lornet, Guillaume De Winter, Vicky Timmerman, Vincent Lamkanfi, Mohamed Janssens, Sophie |
author_facet | Ydens, Elke Demon, Dieter Lornet, Guillaume De Winter, Vicky Timmerman, Vincent Lamkanfi, Mohamed Janssens, Sophie |
author_sort | Ydens, Elke |
collection | PubMed |
description | BACKGROUND: NOD-like receptors (Nlrs) are key regulators of immune responses during infection and autoimmunity. A subset of Nlrs assembles inflammasomes, molecular platforms that are activated in response to endogenous danger and microbial ligands and that control release of interleukin (IL)-1β and IL-18. However, their role in response to injury in the nervous system is less understood. METHODS: In this study, we investigated the expression profile of major inflammasome components in the peripheral nervous system (PNS) and explored the physiological role of different Nlrs upon acute nerve injury in mice. RESULTS: While in basal conditions, predominantly members of NOD-like receptor B (Nlrb) subfamily (NLR family, apoptosis inhibitory proteins (NAIPs)) and Nlrc subfamily (ICE-protease activating factor (IPAF)/NOD) are detected in the sciatic nerve, injury causes a shift towards expression of the Nlrp family. Sterile nerve injury also leads to an increase in expression of the Nlrb subfamily, while bacteria trigger expression of the Nlrc subfamily. Interestingly, loss of Nlrp6 led to strongly impaired nerve function upon nerve crush. Loss of the inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) and effector caspase-1 and caspase-11 did not affect sciatic nerve function, suggesting that Nlrp6 contributed to recovery after peripheral nerve injury independently of inflammasomes. In line with this, we did not detect release of mature IL-1β upon acute nerve injury despite potent induction of pro-IL-1β and inflammasome components Nlrp3 and Nlrp1. However, Nlrp6 deficiency was associated with increased pro-inflammatory extracellular regulated MAP kinase (ERK) signaling, suggesting that hyperinflammation in the absence of Nlrp6 exacerbated peripheral nerve injury. CONCLUSIONS: Together, our observations suggest that Nlrp6 contributes to recovery from peripheral nerve injury by dampening inflammatory responses independently of IL-1β and inflammasomes. |
format | Online Article Text |
id | pubmed-4528710 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45287102015-08-08 Nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes Ydens, Elke Demon, Dieter Lornet, Guillaume De Winter, Vicky Timmerman, Vincent Lamkanfi, Mohamed Janssens, Sophie J Neuroinflammation Research BACKGROUND: NOD-like receptors (Nlrs) are key regulators of immune responses during infection and autoimmunity. A subset of Nlrs assembles inflammasomes, molecular platforms that are activated in response to endogenous danger and microbial ligands and that control release of interleukin (IL)-1β and IL-18. However, their role in response to injury in the nervous system is less understood. METHODS: In this study, we investigated the expression profile of major inflammasome components in the peripheral nervous system (PNS) and explored the physiological role of different Nlrs upon acute nerve injury in mice. RESULTS: While in basal conditions, predominantly members of NOD-like receptor B (Nlrb) subfamily (NLR family, apoptosis inhibitory proteins (NAIPs)) and Nlrc subfamily (ICE-protease activating factor (IPAF)/NOD) are detected in the sciatic nerve, injury causes a shift towards expression of the Nlrp family. Sterile nerve injury also leads to an increase in expression of the Nlrb subfamily, while bacteria trigger expression of the Nlrc subfamily. Interestingly, loss of Nlrp6 led to strongly impaired nerve function upon nerve crush. Loss of the inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) and effector caspase-1 and caspase-11 did not affect sciatic nerve function, suggesting that Nlrp6 contributed to recovery after peripheral nerve injury independently of inflammasomes. In line with this, we did not detect release of mature IL-1β upon acute nerve injury despite potent induction of pro-IL-1β and inflammasome components Nlrp3 and Nlrp1. However, Nlrp6 deficiency was associated with increased pro-inflammatory extracellular regulated MAP kinase (ERK) signaling, suggesting that hyperinflammation in the absence of Nlrp6 exacerbated peripheral nerve injury. CONCLUSIONS: Together, our observations suggest that Nlrp6 contributes to recovery from peripheral nerve injury by dampening inflammatory responses independently of IL-1β and inflammasomes. BioMed Central 2015-08-08 /pmc/articles/PMC4528710/ /pubmed/26253422 http://dx.doi.org/10.1186/s12974-015-0367-8 Text en © Ydens et al. 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Ydens, Elke Demon, Dieter Lornet, Guillaume De Winter, Vicky Timmerman, Vincent Lamkanfi, Mohamed Janssens, Sophie Nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes |
title | Nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes |
title_full | Nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes |
title_fullStr | Nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes |
title_full_unstemmed | Nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes |
title_short | Nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes |
title_sort | nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528710/ https://www.ncbi.nlm.nih.gov/pubmed/26253422 http://dx.doi.org/10.1186/s12974-015-0367-8 |
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