4.7 Article

Interleukin-17A regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice

Journal

CELL DEATH & DISEASE
Volume 12, Issue 8, Pages -

Publisher

SPRINGERNATURE
DOI: 10.1038/s41419-021-04064-1

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Funding

  1. AMED-CREST [18gm1210005h0001]
  2. JSPS KAKENHI [JP21K07459]

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Ependymal cells have the potential to enhance regeneration processes by secreting neurotrophic factors, with IL-17A negatively regulating this effect. Conditional knockout of IL-17RA in ependymal cells leads to enhanced axonal growth and functional recovery after spinal cord injury. Manipulation of ependymal cells at a molecular level could be a promising strategy for improving functional recovery.
Ependymal cells have been suggested to act as neural stem cells and exert beneficial effects after spinal cord injury (SCI). However, the molecular mechanism underlying ependymal cell regulation after SCI remains unknown. To examine the possible effect of IL-17A on ependymal cell proliferation after SCI, we locally administrated IL-17A neutralizing antibody to the injured spinal cord of a contusion SCI mouse model, and revealed that IL-17A neutralization promoted ependymal cell proliferation, which was paralleled by functional recovery and axonal reorganization of both the corticospinal tract and the raphespinal tract. Further, to test whether ependymal cell-specific manipulation of IL-17A signaling is enough to affect the outcomes of SCI, we generated ependymal cell-specific conditional IL-17RA-knockout mice and analyzed their anatomical and functional response to SCI. As a result, conditional knockout of IL-17RA in ependymal cells enhanced both axonal growth and functional recovery, accompanied by an increase in mRNA expression of neurotrophic factors. Thus, Ependymal cells may enhance the regenerative process partially by secreting neurotrophic factors, and IL-17A stimulation negatively regulates this beneficial effect. Molecular manipulation of ependymal cells might be a viable strategy for improving functional recovery.

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