CNS Repair Requires Both Effector and Regulatory T Cells with Distinct Temporal and Spatial Profiles
| Autor: | Nadine Graubardt, Chen Eitan, Tamara Berkutzki, Michal Schwartz, Anat London, Catarina Raposo, Merav Cohen |
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| Rok vydání: | 2014 |
| Předmět: |
Green Fluorescent Proteins
CX3C Chemokine Receptor 1 Mice Transgenic Biology T-Lymphocytes Regulatory Mice Immune system Antigens CD Leukocyte Trafficking Parenchyma medicine Animals Humans Diphtheria Toxin Spinal cord injury Spinal Cord Injuries Effector Macrophages General Neuroscience Monocyte Vaccination FOXP3 Forkhead Transcription Factors Recovery of Function Articles medicine.disease Spinal cord Peptide Fragments CD11c Antigen Nerve Regeneration Cell biology Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Immunology Myelin-Oligodendrocyte Glycoprotein Receptors Chemokine T-Box Domain Proteins |
| Zdroj: | Journal of Neuroscience. 34:10141-10155 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | Monocyte-derived macrophages (mo-MΦs) 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-γ-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-γ-producing T cells, the CP was not activated, and recruitment of inflammation-resolving mo-MΦ to the spinal cord parenchyma was limited. We further demonstrate that mo-MΦ 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-MΦ. 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. |
| Databáze: | OpenAIRE |
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