| First Author | Raposo C | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 31 | Pages | 10141-55 |
| PubMed ID | 25080578 | Mgi Jnum | J:215779 |
| Mgi Id | MGI:5606239 | Doi | 10.1523/JNEUROSCI.0076-14.2014 |
| Citation | Raposo C, et al. (2014) CNS repair requires both effector and regulatory T cells with distinct temporal and spatial profiles. J Neurosci 34(31):10141-55 |
| abstractText | Monocyte-derived macrophages (mo-MPhis) and T cells have been shown to contribute to spinal cord repair. Recently, the remote brain choroid plexus epithelium (CP) was identified as a portal for monocyte recruitment, and its activation for leukocyte trafficking was found to be IFN-gamma-dependent. Here, we addressed how the need for effector T cells can be reconciled with the role of inflammation-resolving immune cells in the repair process. Using an acute spinal cord injury model, we show that in mice deficient in IFN-gamma-producing T cells, the CP was not activated, and recruitment of inflammation-resolving mo-MPhi to the spinal cord parenchyma was limited. We further demonstrate that mo-MPhi locally regulated recruitment of thymic-derived Foxp3(+) regulatory T (Treg) cells to the injured spinal cord parenchyma at the subacute/chronic phase. Importantly, an ablation protocol that resulted in reduced Tregs at this stage interfered with tissue remodeling, in contrast to Treg transient ablation, restricted to the 4 d period before the injury, which favored repair. The enhanced functional recovery observed following such a controlled decrease of Tregs suggests that reduced systemic immunosuppression at the time of the insult can enhance CNS repair. Overall, our data highlight a dynamic immune cell network needed for repair, acting in discrete compartments and stages, and involving effector and regulatory T cells, interconnected by mo-MPhi. Any of these populations may be detrimental to the repair process if their level or activity become dysregulated. Accordingly, therapeutic interventions must be both temporally and spatially controlled. |
