Interleukin-17 impedes Schwann cell-mediated myelination
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JOURNAL OF NEUROINFLAMMATION
RESEARCH
Open Access
Interleukin-17 impedes Schwann cell-mediated myelination Mark Stettner*, Birthe Lohmann, Kathleen Wolffram, Jan-Philipp Weinberger, Thomas Dehmel, Hans-Peter Hartung, Anne K Mausberg and Bernd C Kieseier
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 SCrelevant 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. Keywords: dorsal root ganglia, myelin, IL-17, Guillain-Barré syndrome, inflammatory neuropathy
Background Immune-mediated neuropathies represent a heterogeneous group of mainly demyelinating conditions, including chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain-Barré syndrome (GBS). Both conditions are caused by an autoimmune response to peripheral nerve antigens leading to inflammation, followed by glial and neuronal damage. The underlying molecular mechanism of these diseases still remains mainly unclear. Interleukin (IL)-17 exhibits relevant effects during inflammation in the peripheral nervous system (PNS) [1]. In addition, in chronic constriction injury of the sciatic nerve, IL-17+ T cells have been detected in the endoneurium, * Correspondence: [email protected] Department of Neurology, Medical Faculty, Research Group for Clinical and Experimental Neuroimmunology, Heinrich-Heine-University, Moorenstraße 5, 40225 Düsseldorf, Germany
and contribute to myelin dam
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