Ly6C+ Ly6G- Myeloid-derived suppressor cells play a critical role in the resolution of acute inflammation and the subsequent tissue repair process after spinal cord injury

J Neurochem. 2013 Apr;125(1):74-88. doi: 10.1111/jnc.12135. Epub 2013 Jan 15.

Abstract

Acute inflammation is a prominent feature of central nervous system (CNS) insult and is detrimental to the CNS tissue. Although this reaction spontaneously diminishes within a short period of time, the mechanism underlying this inflammatory resolution remains largely unknown. In this study, we demonstrated that an initial infiltration of Ly6C(+) Ly6G(-) immature monocyte fraction exhibited the same characteristics as myeloid-derived suppressor cells (MDSCs), and played a critical role in the resolution of acute inflammation and in the subsequent tissue repair by using mice spinal cord injury (SCI) model. Complete depletion of Ly6C(+) Ly6G(-) fraction prior to injury by anti-Gr-1 antibody (clone: RB6-8C5) treatment significantly exacerbated tissue edema, vessel permeability, and hemorrhage, causing impaired neurological outcomes. Functional recovery was barely impaired when infiltration was allowed for the initial 24 h after injury, suggesting that MDSC infiltration at an early phase is critical to improve the neurological outcome. Moreover, intraspinal transplantation of ex vivo-generated MDSCs at sites of SCI significantly reduced inflammation and promoted tissue regeneration, resulting in better functional recovery. Our findings reveal the crucial role of an Ly6C(+) Ly6G(-) fraction as MDSCs in regulating inflammation and tissue repair after SCI, and also suggests an MDSC-based strategy that can be applied to acute inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antigens, Ly / metabolism*
  • Female
  • Granulocytes / metabolism
  • Granulocytes / pathology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / metabolism
  • Monocytes / pathology
  • Myeloid Cells / metabolism
  • Myeloid Cells / pathology*
  • Myeloid Cells / transplantation
  • Neovascularization, Physiologic
  • Receptors, Chemokine / immunology
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology

Substances

  • Antibodies
  • Antigens, Ly
  • Gr-1 protein, mouse
  • Ly-6C antigen, mouse
  • Ly6G antigen, mouse
  • Receptors, Chemokine