CD200R1 Contributes to Successful Functional Reinnervation after a Sciatic Nerve Injury

Cells. 2022 May 30;11(11):1786. doi: 10.3390/cells11111786.

Abstract

Activating and inhibitory immune receptors play a critical role in regulating systemic and central nervous system (CNS) immune and inflammatory processes. The CD200R1 immunoreceptor induces a restraining signal modulating inflammation and phagocytosis in the CNS under different inflammatory conditions. However, it remains unknown whether CD200R1 has a role in modulating the inflammatory response after a peripheral nerve injury, an essential component of the successful regeneration. Expression of CD200R1 and its ligand CD200 was analyzed during homeostasis and after a sciatic nerve crush injury in C57Bl/6 mice. The role of CD200R1 in Wallerian Degeneration (WD) and nerve regeneration was studied using a specific antibody against CD200R1 injected into the nerve at the time of injury. We found an upregulation of CD200R1 mRNA after injury whereas CD200 was downregulated acutely after nerve injury. Blockade of CD200R1 significantly reduced the acute entrance of both neutrophils and monocytes from blood after nerve injury. When long term regeneration and functional recovery were evaluated, we found that blockade of CD200R1 had a significant effect impairing the spontaneous functional recovery. Taken together, these results show that CD200R1 has a role in mounting a successful acute inflammatory reaction after injury, and contributes to an effective functional recovery.

Keywords: CD200R1 blocking antibody; Wallerian Degeneration; functional reinnervation; immune receptor; macrophages; regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Mice
  • Nerve Crush
  • Nerve Regeneration*
  • Orexin Receptors* / metabolism
  • Peripheral Nerve Injuries*
  • Phagocytosis / genetics
  • Sciatic Nerve

Substances

  • Cd200r1 protein, mouse
  • Orexin Receptors

Grants and funding

This work has been supported by grants from Comisión Sectorial de Investigación Científica (CSIC-UDELAR), Uruguay; PEDECIBA, Uruguay; FOCEM (MERCOSUR Structural Convergence Fund), COF 03/1111; and Banco de Seguros del Estado (BSE), Uruguay; Spanish Ministry of Science and Innovation (PID2020-PID2020-120267RB-I00/AEI/1013039/501100011033) and RICORS (R21/0017/008). J.A.-A. is the recipient of a FPU fellowship. R.L.-V. is the recipient of an ICREA Academia Award (Generalitat de Catalunya, 2022–2026). N.L. is a recipient of a Marie Skłodowska-Curie Individual Fellowships (H2020-MSCA-IF-2020 number 101030280).