Effect of M2 macrophage adoptive transfer on transcriptome profile of injured spinal cords in rats

Exp Biol Med (Maywood). 2019 Aug;244(11):880-892. doi: 10.1177/1535370219854668. Epub 2019 Jun 3.

Abstract

The previous studies showed that alternatively activated anti-inflammatory macrophage (M2) adoptive immunity can improve the proportion of local M2 cells and play the neuroprotective effect after spinal cord injury (SCI). Its molecular mechanism is not yet very clear. Therefore, this study aims to analyze the effect of the M2 adoptive transfer on the local expression of gene transcription. Sprague-Dawley (SD) rats were used for culture of macrophages and establishment of SCI models. After SCI, the polarized M2 macrophages were transferred to the injured rats by tail vein injection. Seven days after operation, the differentially expressed genes (DEGs) in the spinal cords were analyzed by RNA-sequencing (RNA-Seq). Then, the functional enrichment analysis and pathways were performed by using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), respectively. RNA-Seq showed that M2 adoptive immunity can down-regulate many well-studied gene expressions associated with signaling pathways of inflammatory, such as antigen processing and presentation, phagosome, cell adhesion molecules, natural killer cell-mediated cytotoxicity, endocytosis, proteasome, and Toll-like receptor signaling pathway. These may explain the mechanism of our previous adoptive immunization of M2 cells to provide neuroprotection for SCI. In addition, a novel pathway, retinoic acid-inducible gene-1 (RIG-I)-like receptor signaling pathway was found to be involved in the pathological process of SCI and the response to M2 adoptive immunity as well. This will provide a new explanation for the pathological mechanism of SCI and a new theoretical and experimental basis for its clinical treatment. The raw Illumina data are available at http://www.ncbi.nlm.nih.gov/sra (accession number PRJNA517238).

Impact statement: This research aimed to analyze the effect of M2 macrophage adoptive transfer on the local expression of gene transcription after SCI by RNA-Seq. The results showed that M2 adoptive immunity can down-regulate many well-studied gene expressions associated with signaling pathways of inflammatory. These may explain the mechanism of our previous adoptive immunization of M2 cells to provide neuroprotection for SCI. In addition, a novel pathway, RIG-I-like receptor signaling pathway was also found to involve in the pathological process of SCI and the response to M2 adoptive immunity. This will provide a new explanation for the pathological mechanism of SCI and a new theoretical and experimental basis for its clinical treatment.

Keywords: M2 macrophages; RNA-sequencing; Spinal cord injury; adoptive transfer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / genetics
  • Adaptive Immunity / immunology*
  • Adoptive Transfer / methods
  • Animals
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Female
  • Inflammation / genetics
  • Inflammation / immunology
  • Macrophages / immunology*
  • Neuroprotective Agents / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Spinal Cord / immunology
  • Spinal Cord Injuries / genetics
  • Spinal Cord Injuries / immunology*
  • Toll-Like Receptors / genetics
  • Transcriptome / genetics*
  • Transcriptome / immunology

Substances

  • Neuroprotective Agents
  • Toll-Like Receptors