Interleukin-17 impedes Schwann cell-mediated myelination

Mark Stettner,Kathleen Wolffram,Thomas Dehmel,Birthe Lohmann,Anne K Mausberg,Jan-Philipp Weinberger,Hans-Peter Hartung,Bernd C Kieseier

doi:10.1186/1742-2094-11-63

Mark Stettner, Kathleen Wolffram + Show 6 more

Open Access

https://doi.org/10.1186/1742-2094-11-63

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Abstract

BackgroundPro-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.MethodsHere, 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.ResultsSCs 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.ConclusionsIL-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.

Highlights

Pro-inflammatory cytokines are known to have deleterious effects on Schwann cells (SCs)
Schwann cells express Interleukin 17 (IL-17) receptors To evaluate the molecular target of IL-17, IL-17R A and IL-17R B were analyzed on SCs using immunocytochemistry
(See figure on previous page.) Figure 2 Myelin morphology and quantification after interleukin 17 (IL-17) treatment. (A-E) For myelin quantification, mouse dorsal root ganglia (DRG) co-cultures were exposed to IL-17 for 21 days at the indicated concentrations and subsequently stained, using Sudan black dye

Summary

Introduction

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. Immune-mediated neuropathies represent a heterogeneous group of mainly demyelinating conditions, including chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain-Barré syndrome (GBS). 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. Chi et al detected an increase in Th17+ cell populations in the CSF of active CIDP patients [10] These results suggest an involvement of IL-17 during the active and demyelinating phase of the disease

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