RESUMO
Inhibition of dendritic cell maturation and activation, together with abnormal functioning of cell-mediated immunity, has been reported in chronic spinal cord injury (SCI). The development of immune-based therapies could: 1) prevent or slow down limit further tissue damage in chronic SCI, and 2) promote tissue regeneration. To identify novel candidate molecular pathways mediating SCI-induced immune changes, we performed whole-genome microarray and molecular pathway analyses. Subjects with motor complete chronic SCI (> 2 years post-injury) and uninjured controls were selected from an ongoing study. Microarray analysis was performed with RNA extracted from circulating monocytes. Partek Genomic Suite (PGS) software was used to limit the 54,000 gene list to only those genes up-regulated or down-regulated by 2-fold or more in SCI compared with control. Pathway analyses were performed with Ingenuity Systems IPA software to identify biological pathways of interest involving differentially expressed genes. Genes of interest were then confirmed by quantitative PCR (qPCR). Six SCI subjects and five uninjured controls were included in the final analyses. A molecular pathway related to immune cell trafficking was identified as being significantly upregulated in the SCI subjects. Two genes in that network, transmembrane domain protein (TMEM)176A and TMEM176B, were notable for the magnitude of overexpression. Dendritic cells have been shown to mediate recovery and/or protective autoimmunity in central nervous system injuries and have the capacity to induce neuroprotection and neurogenesis in stroke patients. High TMEM176A and TMEM176B levels have been shown to prevent dendritic cell maturation and inhibit dendritic cell activity in the general population. Here, we report overexpression of both genes in SCI compared with control subjects. Thus, we propose that TMEM176A and TMEM176B are candidate genes involved in inhibiting protective immune responses in SCI. This study may support future research aimed at developing new targets for therapies to promote immune system-mediated neuroprotection and recovery in SCI.