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

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.

Identification of serum exosomal microRNAs in acute spinal cord injured rats

“…A T9 moderate contusive SCI model was performed by using an Infinite Horizon impactor (Precision Systems & Instrumentation, Lexington, KY) according to our previous method. 32 In SCI group, the exposed spinal cord was impacted with a force of 120 kdynes and a dwell time of zero seconds. In sham group, the rats only received a laminectomy without contusion.…”

M2-like macrophages transplantation protects against the doxorubicin-induced heart failure via mitochondrial transfer

“…M2 macrophages were reported to secrete enzymes [ 24 , 25 ] cytokines [ 9 , 12 ], peptides [ 26 ], exosomes [ 27 ] which could mediate its beneficial effects. What’s more, local M2-like macrophages participated in some signal pathways, including NF-kB [ 28 ], and RIG-I [ 29 ] and regulated Treg and Th17 cell responses [ 30 ]. Similarly, our results found M2-like macrophages transplantation induced Th2 response as evidenced by more filtration of IL4 + or GATA3 + CD4 + T cells.…”

Hematogenous Macrophages: A New Therapeutic Target for Spinal Cord Injury

“…Exosomes not only promote the polarization of anti-inflammatory microglia but also have neuroprotective effects and induce autophagy by downregulating the PI3K/AKT/mTOR signaling pathway ( Huang 2019 ). Since M2 macrophages can produce anti-inflammatory cytokines and promote angiogenesis, Chen et al adopted the method of transferring M2 to the injured spinal cord, which promoted neural development of injured spinal cord and inhibited neuronal death by regulating nucleoli and ribosome biogenesis ( Chen et al, 2019 ). Similarly, in retinal injury, the direct transfer of naive monocytes to the injured mice also promotes neuroprotection and the renewal of retinal progenitor cells ( London et al, 2011 ).…”