title: Nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes.
abstract: 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.
authors.affiliation: Peripheral Neuropathy Group, Department of Molecular Genetics, VIB and University of Antwerp, Universiteitsplein 1, B-2610, Wilrijk, Antwerpen, Belgium. Elke.ydens@uhasselt.be.|Neurogenetics Laboratory, Institute Born-Bunge and University of Antwerp, Universiteitsplein 1, B-2610, Antwerpen, Belgium. Elke.ydens@uhasselt.be.
authors.forename: Elke
authors.initials: E
authors.lastname: Ydens
authors.affiliation: Department of Medical Protein Research, VIB, Gent, Belgium. Dieter.demon@vib-ugent.be.|Department of Biochemistry, Ghent University, Gent, Belgium. Dieter.demon@vib-ugent.be.
authors.forename: Dieter
authors.initials: D
authors.lastname: Demon
authors.affiliation: Unit Immunoregulation and Mucosal Immunology, GROUP-ID Consortium, VIB Inflammation Research Centre, Technologiepark 927, B-9052, Gent, Belgium. Guillaume.lornet@irc.vib-ugent.be.|Department of Internal Medicine, Ghent University, Gent, Belgium. Guillaume.lornet@irc.vib-ugent.be.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lornet
authors.affiliation: Peripheral Neuropathy Group, Department of Molecular Genetics, VIB and University of Antwerp, Universiteitsplein 1, B-2610, Wilrijk, Antwerpen, Belgium. Vicky.dewinter@molgen.vib-ua.be.|Neurogenetics Laboratory, Institute Born-Bunge and University of Antwerp, Universiteitsplein 1, B-2610, Antwerpen, Belgium. Vicky.dewinter@molgen.vib-ua.be.
authors.forename: Vicky
authors.initials: V
authors.lastname: De Winter
authors.affiliation: Peripheral Neuropathy Group, Department of Molecular Genetics, VIB and University of Antwerp, Universiteitsplein 1, B-2610, Wilrijk, Antwerpen, Belgium. Vincent.timmerman@molgen.vib-ua.be.|Neurogenetics Laboratory, Institute Born-Bunge and University of Antwerp, Universiteitsplein 1, B-2610, Antwerpen, Belgium. Vincent.timmerman@molgen.vib-ua.be.
authors.forename: Vincent
authors.initials: V
authors.lastname: Timmerman
authors.affiliation: Department of Medical Protein Research, VIB, Gent, Belgium. Mohamed.lamkanfi@vib-ugent.be.|Department of Biochemistry, Ghent University, Gent, Belgium. Mohamed.lamkanfi@vib-ugent.be.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Lamkanfi
authors.affiliation: Unit Immunoregulation and Mucosal Immunology, GROUP-ID Consortium, VIB Inflammation Research Centre, Technologiepark 927, B-9052, Gent, Belgium. Sophie.janssens@irc.vib-ugent.be.|Department of Internal Medicine, Ghent University, Gent, Belgium. Sophie.janssens@irc.vib-ugent.be.
authors.forename: Sophie
authors.initials: S
authors.lastname: Janssens
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D058847:Inflammasomes / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009409:Nerve Crush; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000473:pathology* / Q000523:psychology; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics*; D020127:Recovery of Function; D012584:Sciatic Nerve / Q000473:pathology
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C559901:Nod-like receptor pyrin domain-containing protein 6, mouse; D011956:Receptors, Cell Surface