Neutrophils express oncomodulin and promote optic nerve regeneration

Takuji Kurimoto, Yuqin Yin, Ghaith Habboub, Hui Ya Gilbert, Yiqing Li, Shintaro Nakao, Ali Hafezi-Moghadam, Larry I. Benowitz

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85 Citations (Scopus)

Abstract

Although neurons are normally unable to regenerate their axons after injury to the CNS, this situation can be partially reversed by activating the innate immune system. In a widely studied instance of this phenomenon, proinflammatory agents have been shown to cause retinal ganglion cells, the projection neurons of the eye, to regenerate lengthy axons through the injured optic nerve. However, the role of different molecules and cell populations in mediating this phenomenon remains unclear. We show here that neutrophils, the first responders of the innate immune system, play a central role in inflammation-induced regeneration. Numerous neutrophils enter the mouse eye within a few hours of inducing an inflammatory reaction and express high levels of the atypical growth factor oncomodulin (Ocm). Immunodepletion of neutrophils diminished Ocm levels in the eye without altering levels of CNTF, leukemia inhibitory factor, or IL-6, and suppressed the proregenerative effects of inflammation. A peptide antagonist of Ocm suppressed regeneration as effectively as neutrophil depletion. Macrophages enter the eye later in the inflammatory process but appear to be insufficient to stimulate extensive regeneration in the absence of neutrophils. These data provide the first evidence that neutrophils are a major source of Ocm and can promote axon regeneration in the CNS.

Original languageEnglish
Pages (from-to)14816-14824
Number of pages9
JournalJournal of Neuroscience
Volume33
Issue number37
DOIs
Publication statusPublished - 2013

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Kurimoto, T., Yin, Y., Habboub, G., Gilbert, H. Y., Li, Y., Nakao, S., Hafezi-Moghadam, A., & Benowitz, L. I. (2013). Neutrophils express oncomodulin and promote optic nerve regeneration. Journal of Neuroscience, 33(37), 14816-14824. https://doi.org/10.1523/JNEUROSCI.5511-12.2013