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Toll-Like Receptor 3 Contributes to Wallerian Degeneration after Peripheral Nerve Injury
- Toll-Like Receptor 3 Contributes to Wallerian Degeneration after Peripheral Nerve Injury
- Lee, H[Lee, Hyunkyoung]; Baek, J[Baek, Jiyeon]; Min, H[Min, Hyunjung]; Cho, IH[Cho, Ik-Hyun]; Yu, SW[Yu, Seong-Woo]; Lee, SJ[Lee, Sung Joong]
- DGIST Authors
- Yu, SW[Yu, Seong-Woo]
- Issue Date
- NeuroImmunoModulation, 23(4), 209-216
- Article Type
- Chemokine; Macrophage Recruitment; Schwann Cells; Sciatic Nerve Injury; Toll-Like Receptor3; Wallerian Degeneration
- Objective: It is well known that Schwann cells play an important role in Wallerian degeneration after peripheral nerve injury. Previously, we reported that toll-like receptor 3 (TLR3) is expressed on Schwann cells, implicating its role in Schwann cell activation during Wallerian degeneration. In this study, we tested this possibility using TLR3 knock-out mice. Methods: Sciatic nerve-crush injury was induced in wild-type and TLR3 knock-out mice. Histological sections of the sciatic nerve were analyzed for Wallerian degeneration on days 3 and 7 after injury. The level of macrophage infiltration was measured by real-time RT-PCR, flow cytometry and immunohistochemistry. The macrophage-recruiting chemokine gene expressions in the injured nerve were determined by real-time RT-PCR. Results: In TLR3 knock-out mice, the nerve injury-induced axonal degeneration and subsequent axonal debris clearance were reduced compared to in wild-type mice. In addition, nerve injury-induced macrophage infiltration into injury sites was attenuated in TLR3 knock-out mice and was accompanied by reduced expression of macrophage-recruiting chemokines such as CC-chemokine ligands (CCL)2/MCP-1, CCL4/MIP-1β and CCL5/RANTES. These macrophage-recruiting chemokines were induced in primary Schwann cells upon TLR3 stimulation. Finally, intraneural injection of polyinosinic-polycytidylic acid, a synthetic TLR3 agonist, induced macrophage infiltration into the sciatic nerve in vivo. Conclusion: These data show that TLR3 signaling contributes to Wallerian degeneration after peripheral nerve injury by affecting Schwann cell activation and macrophage recruitment to injured nerves. © 2016 S. Karger AG, Basel.
- S. Karger AG
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