CD200 modulates spinal cord injury neuroinflammation and outcome through CD200R1

Natalia Lago, Bruno Pannunzio, Jesús Amo-Aparicio, Rubèn López-Vales, Hugo Peluffo

Research output: Contribution to journalArticleResearch

12 Citations (Scopus)

Abstract

© 2018 The interaction between CD200 and its receptor CD200R1 is among the central regulators of microglia and macrophage phenotype. However, it remains to be established whether, in the context of a traumatic CNS injury, CD200R1 act as a negative regulator of these particular innate immune cells, and if the exogenous delivery of CD200 may ameliorate neurological deficits. In the present study, we first evaluated whether preventing the local interaction between the pair CD200-CD200R1, by using a selective blocking antibody against CD200R1, has a role on functional and inflammatory outcome after contusion-induced spinal cord injury (SCI) in mice. The injection of the αCD200R1, but not control IgG1, into the lesioned spinal cord immediately after the SCI worsened locomotor performance and exacerbated neuronal loss and demyelination. At the neuroimmunological level, we observed that microglial cells and macrophages showed increased levels of iNOS and Ly6C upon CD200R1 blockade, indicating that the disruption of CD200R1 drove these cells towards a more pro-inflammatory phenotype. Moreover, although CD200R1 blockade had no effect in the initial infiltration of neutrophils into the lesioned spinal cord, it significantly impaired their clearance, which is a key sign of excessive inflammation. Interestingly, intraparenchymal injection of recombinant CD200-His immediately after the injury induced neuroprotection and robust and long-lasting locomotor recovery. In conclusion, this study reveals that interaction of CD200-CD200R1 plays a crucial role in limiting inflammation and lesion progression after SCI, and that boosting the stimulation of this pathway may constitute a new therapeutic approach.
Original languageEnglish
Pages (from-to)416-426
JournalBrain, Behavior, and Immunity
Volume73
DOIs
Publication statusPublished - 1 Oct 2018

Keywords

  • CD200R1 blocking antibody
  • Immune receptor
  • Microglia
  • Neuroinflammation
  • Neuroprotection
  • OX131
  • Recombinant CD200
  • SCI
  • Therapeutic window

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