title: Interleukin-17 impedes Schwann cell-mediated myelination.
abstract: BACKGROUND
  Pro-inflammatory cytokines are known to have deleterious effects on Schwann cells (SCs). Interleukin 17 (IL-17) is a potent pro-inflammatory cytokine that exhibits relevant effects during inflammation in the peripheral nervous system (PNS), and IL-17-secreting cells have been reported within the endoneurium in proximity to the SCs.
  
  
  METHODS
  Here, we analyzed the effects of IL-17 on myelination and the immunological properties of SCs. Dorsal root ganglia (DRG) co-cultures containing neurons and SCs from BL6 mice were used to define the impact of IL-17 on myelination and on SC differentiation; primary SCs were analyzed for RNA and protein expression to define the putative immunological alignment of the SCs.
  
  
  RESULTS
  SCs were found to functionally express the IL-17 receptors A and B. In DRG cultures, stimulation with IL-17 resulted in reduced myelin synthesis, while pro-myelin gene expression was suppressed at the mRNA level. Neuronal outgrowth and SC viability, as well as structural myelin formation, remained unaffected. Co-cultures exhibited SC-relevant pro-inflammatory markers, such as matrix metalloproteinase 9 and SCs significantly increased the expression of the major histocompatibility complex (MHC) I and exhibited a slight, nonsignificant increase in expression of MHCII, and a transporter associated with antigen presentation (TAP) II molecules relevant for antigen processing and presentation.
  
  
  CONCLUSIONS
  IL-17 may act as a myelin-suppressive mediator in the peripheral nerve, directly propagating SC-mediated demyelination, paralleled by an inflammatory alignment of the SCs. Further analyses are warranted to elucidate the role of IL-17 during inflammation in the PNS in vivo, which could be useful in the development of target therapies.
authors.affiliation: Department of Neurology, Medical Faculty, Research Group for Clinical and Experimental Neuroimmunology, Heinrich-Heine-University, Moorenstraße 5, 40225 Düsseldorf, Germany. mark.stettner@med.uni-duesseldorf.de.
authors.forename: Mark
authors.initials: M
authors.lastname: Stettner
authors.forename: Birthe
authors.initials: B
authors.lastname: Lohmann
authors.forename: Kathleen
authors.initials: K
authors.lastname: Wolffram
authors.forename: Jan-Philipp
authors.initials: JP
authors.lastname: Weinberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Dehmel
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Anne K
authors.initials: AK
authors.lastname: Mausberg
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D005727:Ganglia, Spinal / Q000166:cytology; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000378:metabolism*; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012583:Schwann Cells / Q000502:physiology* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000166:cytology
chemical_list: D000906:Antibodies; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9